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Marty Chilberg
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Marty Chilberg is a seasoned financial professional with over 30 years of executive leadership, board, consulting and advisory experience.  He began his career as a certified public accountant (CPA). He moved to Silicon Valley in 1981 to begin his career in the software industry, working for... More
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  • TeleCommunication Systems Inc Q2-2015 Another Step Forward

    Telecomsys (NASDAQ:TSYS) reported another quarter of solid results for June 2015. Revenue was up 7% sequentially and 2% Y/Y, though about 2% below analyst consensus.

    NonGAAP earnings, GAAP earnings and adjusted EBITDA were all better than expected. Earnings beat was $0.02 versus consensus expectations of $0.03.

    Company guidance for CY 2015 was reconfirmed aside from a small increase in expected net income.

    The transcript from the earnings conference call was published with numerous transcription errors. My edited version can be found here.

    Highlights from the conference call:

    • The company is close to announcing several government awards with an aggregate value in excess of $150 million. These awards are expected to be split between systems (recognized over the next 12 months) and services (recognized over 3-5 years).
    • Tropo system sales have been delayed and are now expected to roll into 2016 for larger deliveries.
    • SNAP and SNAP reset orders were better than expectations offsetting the delay in Tropo deliveries.
    • The initial domestic order supporting FirstNet implementation was received for connected law enforcement.
    • The company expects to showcase a new Indoor Location engine and National Emergency Address Database (NEAD) developed with Cisco (NASDAQ:CSCO) at the August APCO trade show.
    • TCS is also collaborating with Cisco on several new products for the IoE.
    • Several VirtuMedix customer implementations occurred during the quarter including the first international order. The pipeline was described as "healthy"
    • Several ESInet orders were received subsequent to quarter end.
    • There was no update on the Board committee looking at strategic alternatives to enhance shareholder value.
    Jul 31 9:11 AM | Link | Comment!
  • TeleCommunication Systems, Inc Q2 2015 Earnings Conference Call Edited

    TeleCommunication Systems, Inc. (NASDAQ:TSYS)

    Q2 2015 Earnings Conference Call

    July 30, 2015 17:00 ET

    Maurice Tose - CEO

    The first half of 2015, $16.6 million of adjusted EBITDA was achieved despite over $1 million of non-recurring accounting and legal fees which we reported last quarter without which our first half '15 EBITDA would have been higher than last year's first half. We managed first half expenses commeasured with volume while sustaining investments in R&D to ensure that our portfolio is positioned to capture major long-term opportunities in secure highly reliable wireless. We expect our long term investments in new generation ground terminals for government customers to result in strong second half volume and we are on-track to meet our 2015 objectives.

    Revenue, EBITDA, and net income, all increased quarter-over-quarter. We knew that 2015 would be a backend loaded year, as have been many previous years with the government funding cycle around a September 30, fiscal year-end drives our calendar third and fourth quarter volumes, mainly in shipments of systems and components. Our 2015 federal customer procurement environment has improved as departments operate with an approved federal budget. We now expect our government segment to close multiple contract awards in the near term with an aggregate value in excess of $150 million.

    We've also recently received a master service agreement award to provide our links vehicle router and implementation services. Our first domestic project supporting the FirstNet LTE band for connected law enforcement. We announced earlier this month that our Board has formed a special committee to explore strategic alternatives to enhance shareholder value. As we said in that announcement, no timetable has been set for this evaluation and there is no certainty that this review will result in any particular transaction. We do not plan to comment further until special committee determines that disclosure is necessary or appropriate.

    Turning to some more detail comments on second quarter operating results. During the quarter we continued accelerating the deployment of our 911 technology or WiFi calling. Carriers are eager to offer this service due to the cost efficiencies associated with offloading their wireless networks in congested urban areas, but a key part of the service is making 911 service available. In addition, WiFi calling infrastructure is complimentary to the evolving FCC indoor location requirements, and a development that carriers are watching closely.

    As with their LTE and older networks, operators are turning to TCS to 911-enable this new voice calling service. The first of our customers Voice-over-WiFi 911 enablement services launched earlier this quarter. And we expect significant carrier marketing campaigns to drive additional rollouts in coming months. During the quarter, wireless operator cell side deployments from Voice-over-LTE 911 accelerated. We expect the accelerated roll out of Voice-over-LTE 911 and the realization of forecasted adoption of voice over WiFi by wireless subscribers to continue in the second half of '15.

    We continue to lead the industry in SMS-911 technology for network operated compliance with FCC rules in voluntary commitments. TCS has now completed PSAP deployments approaching 10% of the nation's public safety answering points in 34 states, Puerto Rico and the District of Columbia. We are developing solutions to assist wireless carriers in complying with the FCC's Location Accuracy Order adopted in January 2015 in response to the volume of Wireless-911 calls coming from the indoor environments, both residential and enterprise.

    At the August APCO industry tradeshow, TCS in cooperation with Cisco, will unveil a state-of-the-art indoor location demonstration that is another industry first, incorporating both a prototype National Emergency Address Database, or NEAD, as well as an indoor location engine. This demonstration provides the first working example of elements of the Indoor Location National Architecture that emergency services standard bodies have been working towards.

    In Next Generation-911, we continue to see an increase in state-wide and local projects. TCS provides ESInets, that is: NENA i3 standards compliant Emergency Services IP Network infrastructure and internet protocol handling stations, either on a hosted or end customer network basis. Our Next-Gen footprint is growing in Texas, California, Connecticut, Florida, Iowa, and Tennessee. New for the quarter is a multi-year award to extend our professional services for the State of Tennessee, and we closed a multi-year contract to expand our Florida ESInet to service additional PSAPs.

    We continue to execute on the state-wide deployment of both call handling and ESInet in South Dakota under a five-year $16 million program. Subsequent to quarter close, we closed three additional ESInet deals with an aggregate value in excess of $7 million. We continue to make inroads with our 4G LTE location platforms with several carriers now on board as TCS customers. We see a lot of opportunity for new related functionality into existing customers such as our new LTE Gateway that provides an early warning service in Australia. This enables notice of events such as severe weather or school closings. We also foresee expansion of our addressable market as carriers in Asia and Europe spin to improve their wireless networks.

    During the quarter, we made a small investment to obtain positioning algorithms developed under the Loctronix brand which enables TCS to enhance our indoor location data for applications ranging from advertising and marketing, to navigation and public safety. The resulting indoor location technology allows us to provide a software-based ubiquitous mobile device location, outdoors or indoors, including XY and Z access information.

    In Q2 we launched services for several new VirtuMedix customers throughout the United States and have a healthy pipeline. Our VirtuMedix teleMedicine platform provides patients access to health services anytime, anywhere and from any device. We signed our first international deal demonstrating VirtuMedix versatility to help patients and healthcare providers throughout the world.

    The number of issued patents owned by TCS at the end of the quarter was 418, up 23, and we filed 16 US patent applications during the quarter. This portfolio protects our products, provides opportunities for royalties, and assists us in defending claims against our products directly and under identification provisions of contract with major customers.

    In the second quarter, we entered into an agreement with an entity that offers patent risk solutions, and as a result, two ongoing patent claims that TCS was defending were dismissed. We expect that this approach will help reduce our net expense arising from indemnification claims.

    Government segment revenue for the second quarter was up 19% over Q1 to $44 million, and gross profit was up 9% to $9 million or 20% of revenue from higher sales of systems and components. As noted earlier, we expect our government segment to close multiple services and systems contracts awards in the near term with an aggregate value in excess of $150 million. In 2015, arrangements from VSAT, Baseman, and Microstat system shipments that have been progressing through the procurement processes through the first half will result in imminent delivery releases for which we have prepared to make prompt shipment.

    And during July, we have already booked over $17 million in service orders, including the option year two renewal of the Marine Corp's's global KU managed services contract - managed satellite services contract.

    Our sales pipeline is growing as we see more RFP activity under our client contract vehicles during the government buying season. TCS is expecting to close multiple large scale contract awards under the GTAC IDIQ contract vehicle in the second half of 2015. As such the second quarter-end $63 million of funded backlog is not a good indicator of the outlook for second half volume.

    During the quarter, ISACA announced the commercial offering or their new CyberNexus Certification Program which is powered by TCS's performance score courseware tool, and classes have been scheduled, both domestically and abroad. ISACA is a non-profit global association serving 140,000 professionals in 180 countries, and it's a thought leader in the development, adoption and use of globally accepted industry leading certifications for information systems professionals.

    For professionals seeking DoD work, our tool is the leader. In compliance with DoD's new role based competency, 81-40 standard still preceding older certifications deemed deficient by the National Institute of Standard and Technology. Testing and certifications are expected to conform to the new standard which defined categories and job titles much more explicitly. TCS generates revenue in cyber security training through the development of course content, right-to-use licenses for performance score, integration of performance score into labs and exams, and course instruction.

    Beyond training work, our team of cyber security experts is building a growing list of references for vulnerability assessment work, including critical infrastructure, public safety, financial institutions, and academia.

    In the second quarter, the State of Maryland, Department of Human Resources awarded TCS an $11.3 million state-wide technical operations support services contract to enhance the DHR services to secure their computing environment. In addition to the $14.2 million Marine CorPmanaged satellite services renewal early this month, we were also awarded an initial seven location bandwidth contract in support of SITCOM through a new small business partner for retinal scanning and identification support for the US Army, which we expect to grow to 50 to 100 locations in the SITCOM AOR.

    We expect renewals of contracts covering most of our field service representatives deployed outside the continental US and see growth in such work through the Army Tactical Coms program executive office located at improvement ground here in Maryland.

    The army's program to reset and upgrade the installed base of TCS provided SNAP ground terminals continues to be a steady source of business. The army intends to use snap systems as a bridge to its next generation, transportable, tactical, command communication solutions. Of the 849 systems deployed, TCS has reset 169 systems, and expects the task order later this quarter under the GTAC contract vehicle to perform 360 additional resets over the next three years. Much of our expected systems business in the second half of 2015 is SNAP, SNAP Resets and components.

    TCS continues to work with the army and marines to replace track 170 to Tropo scatter systems. TCS is supplying orders for about $4.5 million of our TROPO scatter systems which will bring the number of worldwide deployed TCS system to 49. The demand for our transit case deployable TROPO product remains high with the Airforce, Army, International Guard and Marine Corp stating demands for upward of 500 systems.

    TCS has been working with Lockheed Martin in Northern since 2012 to develop an affordable terminal using protected, advanced, extremely high frequency communications or AEHF for highly global tactical military forces. These terminals are made less expensive than currently filled protective communications terminals by using commercial technologies to drive down cost.

    In the second quarter, the team successful completed the critical design review for the information assurance elements of the terminal, and is planning to conduct an over the air test with AEHF satellite by the end of this calendar year.

    Full NSA certification is expected in early 2016 with first system sales later next year. We believe the LCT, AEHF terminal-addressable market is north of $2 billion. TCS is collaborating with Cisco to develop new products for the Internet of Everything solutions, incorporating from all parts of TCS. We recently launched our Links to E-Mobile router which extends networks to the mobile platform and the dismounted end user.

    We have recently being awarded a master contract by The Los Angeles County Regional Interoperable Communication Systems Authority or LA-RICS for public safety, broadband network devices.

    LA-RICS is the nation's first band 14 network which is public safety's broadband allocation which is funded by Broadband Technology Opportunity Program Public Safety Federal Grants. This is the same technology described for the Commerce Departments $7 billion FirstNet program to link first responders. We now have ongoing public safety projects in both local and international markets. These projects incorporate TCS's highly mobile and tactical man-wearable router product family which enables vehicles and people to connect to a core network of sensors and applications.

    As with ground terminals, we expect the strong second half from components used in space programs. Domestically we're working on NASA Orion program related projects as well as Japanese space programs leading to revenue visibility through 2017.

    Our government segment has aligned itself in industry partnerships to compete for contract subject to award over the next 12 to 18 months with over a $0.5 billion of multi-year ceiling. Now Tom, will provide some color on the company's financial position and outlook.

    Tom Brandt - CFO

    Thank you, Maurice. The company's practice continues to be to include the details of our quarter on spread sheets posted on the company's website. At quarter-end we had $54 million of cash and securities and $30 million of unused bank credit line availability. As said forth in the press release funds were generated in the quarter by $8.6 million of adjusted EBITDA and that $11.8 million from new capital leases and bank facility borrowings net of debt repayments and $0.2 million from replaced stock options.

    Cash was used during the quarter to fund a $10.5 million increase in working capital mainly for preparation for second half government system sales. $4.2 million was used in CapEx including software development and $2.8 million for cash interest, taxes and other expenses.

    Quarter-end funded backlog was about $300 million of which we expect to recognize a $183 million during the next 12 months. Company's investor relations practice is to provide and update annual guidance for revenue, there is no change to the range or $390 million to $410 million of 2015 revenue versus 2014's $360 million and for adjusted EBITDA we still expect full year results between $38 million and $42 million.

    We're managing the expenses associated with the ongoing examination of strategy alternatives under the direction of the special committee of the board. Most related fee arrangements are contingent on future transactions. If any expenses become significant we will call them out and factor them into our guidance. As Maurice said second half growth is expected to come mainly from government systems and component business that we consider highly visible.

    As I mentioned during our April earnings call, one of our Cellular 911 customers shut down it's network during the second quarter following it's acquisition by another carrier which will affect commercial segment revenue in the third and fourth quarters.

    We also continue to expect 2015 capital expenditures including capitalized software development to be about $15 million to $17 million. We expect non-cash charges for 2015 to total about the same as 2014's $24 million and we now expect cash interest net of other income and expense to be about $8 million, a little less than we predicted earlier in the year due mainly to some favorable first half other income items.

    We paid only state at AMT cash income taxes in 2014 and we came into 2015 with significant NOL and R&D tax credit carry forwards. So we still do not expect to pay any material cash taxes in 2015. We fully reserved our deferred tax asset in 2013 and continue to maintain a full valuation allowance against the asset.

    For 2015 our GAAP tax provision will continue to be unusual, we're now using a 43% effective rate on our expected 2015 pretax income which is mostly represented by non-cash expense.

    Though we now expect an adjusted net income for 2015 will be in the $14 million to $17 million range. We have increased our estimated share count for EPS from 62 million to 63 million shares as a result of higher than planned option exercises.

    The resulting EPS calculation for 2015 is $0.23 to $0.28 per diluted share up from 2014 $0.20. So at this time I will turn the call back to Maurice.

    Maurice Tose - CEO

    Our 2015 continues to shape up well across the company. Market conditions are increasingly favorable for our secure highly-reliable wireless communication technology as we proceed through the year. 911 growth in VoLTE, Voice over WiFi and Next-Gen continues, offsetting the impact of what we view as the last of significant network consolidation and new 911 growth opportunities and indoor location are unfolded. Demand for new location platform is expanding into international markets as we execute on domestic opportunities to replace competitors as customer deploy new 4G wireless technologies.

    Our operating cost for applications are now in-line with revenue and our new product investments. Our government segment portfolio of TCS produced ground terminals, addresses a range of growing defense and public safety communication needs affirming our expected higher volumes and higher margins. In the use of our cyber security courseware is expanding through channels as we continue to apply the scarce skillset to company-wide products for differentiation and competitive advantage.

    So we continue to have confidence in a strong second half performance in 2015 and into following years. Management is working together with the special committee of the Board in exploring strategic alternatives.

    In so doing we continue to foresee double digit year-over-year growth in revenue and operating profit from our core businesses. In looking further into the future we see upside from collaborations to address the convergence of wireless connectivity among phones, computers, sensors, vehicles and people. These new connections will need the cyber security expertise we bring and we believe that our deep relationships with government, with leading network operators and with device companies will provide us the opportunity to create new solutions for this Internet of Everything.

    We thank you for your time and support and we will now would like to open the call to any questions. Operator?

    Question-and-Answer Session

    Mark Jordan - Noble Financial

    Maurice you talked about a significant awards on the governmental side here in the second half. You mentioned a figure of $150 million between services and systems. Could you parse that down to systems versus services and I would assume that the systems would have a very short delivery cycle with services might be a delivery cycle of a year or more. Could you give us some color as to how that breaks down?

    Maurice Tose - CEO

    Well actually systems is expected to be multi-year as well, Mark, and it is roughly almost 50/50 on services and systems.

    Mark Jordan - Noble Financial

    And again any sense of how are the duration of the delivery cycles on both of those?

    Maurice Tose - CEO

    Both of them are multi-year and you know as our typical 3 to 5 year time frames.

    Tom Brandt - CFO

    But Mark, system shipments are naturally faster. So out of that 50/50 your initial observation is sound that -- a lot of that volume on the systems category is going to be realized in the second half and early in '16.

    Maurice Tose - CEO

    Yes, as I said in remarks we have been teeing up for this, this is not catching us flat footed.

    Mark Jordan - Noble Financial

    The unbilled receivables on your balance sheet has gone up about 10 million in the first six months in the year upto about 32 million, just sizeable relative to accounts receivables. What's driving that increase?

    Maurice Tose - CEO

    Little bit of it was a few millions of billing delays in the second quarter but more of it has to do with the timing of the billing terms on some large chunks of shipment of system shipments that we're structured in such a way that it has taken us longer to build than we lack.

    Mark Jordan - Noble Financial

    Final question for me, Maurice, if you went back to, to the year-end call, I think you commented on your portfolio that that the Alice Corp, decision by the Supreme Court back in September of 2014 called into question some of the validities of the some of the software patents that were in the marketplace. So you backed-off on the value of your portfolio and then in the last quarter or two you have seem to emphasize a growing sense of importance. Now is that importance of your growing portfolio patents more as a defensive measure against people coming after you or are you seeing this as a potential incremental revenue source again?

    Maurice Tose - CEO

    Yes. I would say it's in fact both Mark and as we have come to learn and as it indicative in the industry the time for the prosecution and the ultimate award of damages is a long period of time and not very predictable but when it does in fact yield the desired results it is often meaningful. So I will just say it's, both, we were happy again with the analyst decision and in fact one of our products was in fact used to make that argument in that defense. So we are -- we know how to structure patents, to overcome or to increase the probability of overcoming what is perceived as a short comings of Alice.

    Mark Jordan - Noble Financial

    Okay, and then just finally are you placing more emphasis on the formal patent process or is this something that you will deemphasize moving forward?

    Maurice Tose - CEO

    It's pretty steady, Mark, we have been tracking this and it's pretty steady.

    Operator

    And we next move to Glenn Mattson with Ladenburg Thalmann.

    Glenn Mattson - Ladenburg Thalmann

    The number that surprised me to the upside was that the government systems revenue was higher than what I had forecast and the margin stayed pretty high, meaning there wasn't much pass through revenue, can you talk about what drove that? Was it SNAP terminal work or something else?

    Maurice Tose - CEO

    Yes that's exactly right, Glenn, that's been a favorable development in the course of 2015 and it's something that we -- because of the priority that our customers are putting on that design, it looks like it's going to be favorable in the balance of the year.

    Glenn Mattson - Ladenburg Thalmann

    Okay, and then can I ask you -- there was something mentioned about $4 million of tropo systems, was that orders? Or was that -- or completed? Can you clarify that?

    Maurice Tose - CEO

    It's orders. It's orders that we're currently fulfilling and we expect there will be little bit of more in the area of those tropo orders but just I guess with respect to Tropo we have received the few smaller orders totaling $4 million and we expect another in the near term. Unfortunately the larger procurements, actually didn't arrive from our original prediction as a result of multiple services being involved, each with their own competing priorities and processes for procurement authorization, but we're still confident in the scale of Tropo opportunity north of $200 million and expect to see them commence in FY 2016.

    Glenn Mattson - Ladenburg Thalmann

    So is it just a fortunate coincidence, have you guys ever brought products that's -- so I guess this kind of thing can happen but that the -- I think the back half growth was expected to come from tropo but it looks like it's coming from SNAP instead. So is that kind of coincidence that SNAP is filling that gap if tropo kicks in?

    Maurice Tose - CEO

    Yes you've hit it on head, SNAP, SNAP resets and components.

    Operator

    And ladies and gentlemen with no further questions in the queue I would like to turn the conference back over to management for any closing remarks.

    Maurice Tose - CEO

    Well this concludes our 2015 second quarter investment call and we look forward to speaking with you again to discuss third quarter 2015 results.

    Jul 31 8:38 AM | Link | Comment!
  • Patents By Yuk-Ming Dennis Lo
    Diagnosing fetal chromosomal aneuploidy using massively parallel genomic sequencing

    Patent number: 9051616

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

    Type: Grant

    Filed: July 18, 2014

    Issued: June 9, 2015

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    Methods for assessing liver pathologies

    Patent number: 9051614

    Abstract: The present invention provides a new method for detecting or monitoring a liver disease in a subject that has no indication of any liver pathologies, by measuring the amount of concentration of albumin mRNA in an acellular blood sample from the subject, and then comparing the amount or concentration of albumin mRNA with a standard control.

    Type: Grant

    Filed: September 10, 2010

    Issued: June 9, 2015

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu, Rebecca Wing Yan Chan

     

    SEQUENCING ANALYSIS OF CIRCULATING DNA TO DETECT AND MONITOR AUTOIMMUNE DISEASES

    Application number: 20150087529

    Abstract: Systems, methods, and apparatuses are provided for diagnosing auto-immune diseases such as systemic lupus erythematosus (SLE) based on the sizes, methylation levels, and/or genomic characteristics of circulating DNA molecules. Patients provide blood or other tissue samples containing cell-free nucleic molecules for analysis. Massively parallel and/or methylation-aware sequencing can be used to determine the sizes and methylation levels of individual DNA molecules and identify the number of molecules originating from different genomic regions.

    Type: Application

    Filed: September 19, 2014

    Issued: March 26, 2015

    Inventors: Yuk-Ming Dennis LO, Rossa Wai Kwun Chiu, Rebecca Wing Yan Chan, Lai Shan Tam

     

    Diagnosing fetal chromosomal aneuploidy using massively parallel genomic sequencing

    Patent number: 8972202

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

    Type: Grant

    Filed: July 18, 2014

    Issued: March 3, 2015

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    Methods for detecting DNA orginating from different individuals

    Patent number: 8962280

    Abstract: In a first aspect, the present invention features methods for differentiating DNA species originating from different individuals in a biological sample. These methods may be used to differentiate or detect fetal DNA in a maternal sample or to differentiate DNA of an organ donor from DNA of an organ recipient. In preferred embodiments, the DNA species are differentiated by observing epigenetic differences in the DNA species such as differences in DNA methylation. In a second aspect, the present invention features methods of detecting genetic abnormalities in a fetus by detecting fetal DNA in a biological sample obtained from a mother. In a third aspect, the present invention features methods for differentiating DNA species originating from an organ donor from those of an organ recipient. In a fourth aspect, the present invention features kits for differentiating DNA species originating from different individuals in a biological sample.

    Type: Grant

    Filed: April 3, 2013

    Issued: February 24, 2015

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Lit Man Poon

     

    NON-INVASIVE DETERMINATION OF METHYLOME OF TUMOR FROM PLASMA

    Application number: 20150011403

    Abstract: Systems, methods, and apparatuses can determine and use methylation profiles of various tissues and samples. Examples are provided. A methylation profile can be deduced for fetal/tumor tissue based on a comparison of plasma methylation (or other sample with cell-free DNA) to a methylation profile of the mother/patient. A methylation profile can be determined for fetal/tumor tissue using tissue-specific alleles to identify DNA from the fetus/tumor when the sample has a mixture of DNA. A methylation profile can be used to determine copy number variations in genome of a fetus/tumor. Methylation markers for a fetus have been identified via various techniques. The methylation profile can be determined by determining a size parameter of a size distribution of DNA fragments, where reference values for the size parameter can be used to determine methylation levels. Additionally, a methylation level can be used to determine a level of cancer.

    Type: Application

    Filed: September 24, 2014

    Issued: January 8, 2015

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Miu Fan Lun, Wai Man Chan, Peiyong Jiang

     

    Fetal methylation markers

    Patent number: 8927216

    Abstract: This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB2IP, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.

    Type: Grant

    Filed: September 14, 2012

    Issued: January 6, 2015

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Stephen Siu Chung Chim, Chunming Ding, Kwan Chee Chan, Hing Nam Ivy Wong, Ka Chun Ryan Yuen

     

    DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING MASSIVELY PARALLEL GENOMIC SEQUENCING

    Application number: 20140329695

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

    Type: Application

    Filed: July 18, 2014

    Issued: November 6, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING MASSIVELY PARALLEL GENOMIC SEQUENCING

    Application number: 20140329696

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

    Type: Application

    Filed: July 18, 2014

    Issued: November 6, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    DETERMINING FETAL GENOMES FOR MULTIPLE FETUS PREGNANCIES

    Application number: 20140315200

    Abstract: Techniques are provided for determining inheritance of maternal and paternal haplotypes in preganncies with multiple fetuses. Maternal inheritance can be determined at loci where the mother is heterozygous and the paternally inherited alleles are known (e.g., the father is homozygous). Two types of loci may be used, where one type has the paternal allele appear on a first maternal haplotype, and another type has the paternal allele appear on a second maternal haplotype. Paternal inheritance can be determined from loci where the father is heterozygous and the maother is homozygous. Amounts of different alleles at each locus can be measured. A comparison of the amounts (e.g., using a fractional concentration of each allele and cutoffs) can be used to determine the haplotype inheritance. A haplotype can be linked to a condition of interest.

    Type: Application

    Filed: March 17, 2014

    Issued: October 23, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Kwan Chee Chan

     

    METHODS AND KITS FOR SELECTIVELY AMPLIFYING, DETECTING OR QUANTIFYING TARGET DNA WITH SPECIFIC END SEQUENCES

    Application number: 20140302506

    Abstract: Disclosed herein are methods and kits for selectively amplifying, detecting or quantifying a DNA fragment with a specific end sequence, especially generated following restriction enzyme digestion. This method can be used, for example, to detect a hypomethylated DNA fragment. This methods and kits are especially useful in detecting or quantifying a hypomethylated fetal DNA fragment in a maternal plasma sample containing a corresponding hypermethylated maternal DNA fragment.

    Type: Application

    Filed: April 29, 2014

    Issued: October 9, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Yu Kwan Tong, Wai Kwun Rossa Chiu, Chunming Ding

     

    DIAGNOSTIC METHOD

    Application number: 20140272975

    Abstract: The present invention concerns a method for the detection or monitoring of cancer using a biological sample selected from blood, plasma, serum, saliva, urine from an individual, said method comprising: (NYSE:A) obtaining DNA from the said biological sample; (NYSE:B) digesting the DNA sample with one or more methylation-sensitive restriction enzymes; (NYSE:C) quantifying or detecting a DNA sequence of interest after step , wherein the target sequence of interest contains at least two methylation-sensitive restriction enzyme recognition sites; and (NYSE:D) comparing the level of the DNA sequence from the individual to a normal standard, to detect, prognosticate or monitor cancer.

    Type: Application

    Filed: May 22, 2014

    Issued: September 18, 2014

    Assignee: THE CHINESE UNIVERSITY OF HONG KONG

    Inventors: Yuk Ming Dennis LO, Kwan Chee Allen CHAN, Chunming DING

     

    DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING MASSIVELY PARALLEL GENOMIC SEQUENCING

    Application number: 20140256559

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

    Type: Application

    Filed: October 18, 2013

    Issued: September 11, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING MASSIVELY PARALLEL GENOMIC SEQUENCING

    Application number: 20140256560

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

    Type: Application

    Filed: November 22, 2013

    Issued: September 11, 2014

    Assignee: THE CHINESE UNIVERSITY OF HONG KONG

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    MATERNAL PLASMA TRANSCRIPTOME ANALYSIS BY MASSIVELY PARALLEL RNA SEQUENCING

    Application number: 20140243212

    Abstract: Methods are provided for diagnosing pregnancy-associated disorders, determining allelic ratios, determining maternal or fetal contributions to circulating transcripts, and/or identifying maternal or fetal markers using a sample from a pregnant female subject. Also provided is use of a gene for diagnosing a pregnancy-associated disorder in a pregnant female subject.

    Type: Application

    Filed: February 28, 2014

    Issued: August 28, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang, Bo Yin Tsui

     

    DETECTION OF GENETIC OR MOLECULAR ABERRATIONS ASSOCIATED WITH CANCER

    Application number: 20140227699

    Abstract: Systems, apparatus, and methods are provided for determining genetic or molecular aberrations in a biological sample from an organism. Biological samples including cell-free DNA fragments are analyzed to identify imbalances in chromosomal regions, e.g., due to deletions and/or amplifications in a tumor. Multiple loci are used for each chromosomal region. Such imbalances can then be used to diagnose (screen) a patient for cancer, as well as prognosticate a patient with cancer, or to detect the presence or to monitor the progress of a premalignant condition in a patient. The severity of an imbalance as well as the number of regions exhibiting an imbalance can be used. A systematic analysis of non-overlapping segments of a genome can provide a general screening tool for a sample. Additionally, a patient can be tested over time to track severity of each of one or more chromosomal regions and a number of chromosomal regions to enable screening and prognosticating, as well as monitoring of progress (e.g.

    Type: Application

    Filed: April 17, 2014

    Issued: August 14, 2014

    Assignee: THE CHINESE UNIVERSITY OF HONG KONG

    Inventors: Yuk-Ming Dennis Lo, Kwan Chee Chan, Rossa Wai Kwun Chiu, Peiyong Jiang

     

    Methods and kits for selectively amplifying, detecting or quantifying target DNA with specific end sequences

    Patent number: 8748100

    Abstract: Disclosed herein are methods and kits for selectively amplifying, detecting or quantifying a DNA fragment with a specific end sequence, especially generated following restriction enzyme digestion. This method can be used, for example, to detect a hypomethylated DNA fragment. This methods and kits are especially useful in detecting or quantifying a hypomethylated fetal DNA fragment in a maternal plasma sample containing a corresponding hypermethylated maternal DNA fragment.

    Type: Grant

    Filed: August 30, 2007

    Issued: June 10, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Yu Kwan Tong, Wai Kwun Rossa Chiu, Chunming Ding

     

    Detection of genetic or molecular aberrations associated with cancer

    Patent number: 8741811

    Abstract: Biological samples including cell-free DNA fragments are analyzed to identify imbalances in chromosomal regions, e.g., due to deletions and/or amplifications in a tumor. Multiple loci are used for each chromosomal region. Such imbalances can then be used to diagnose (screen) a patient for cancer, as well as prognosticate a patient with cancer, or to detect the presence or to monitor the progress of a premalignant condition in a patient. The severity of an imbalance as well as the number of regions exhibiting an imbalance can be used. A systematic analysis of non-overlapping segments of a genome can provide a general screening tool for a sample. Additionally, a patient can be tested over time to track severity of each of one or more chromosomal regions and a number of chromosomal regions to enable screening and prognosticating, as well as monitoring of progress (e.g. after treatment).

    Type: Grant

    Filed: November 30, 2011

    Issued: June 3, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Peiyong Jiang

     

    Analysis for nucleic acids by digital PCR

    Patent number: 8722334

    Abstract: The present invention provides a method for analyzing nucleic acids for their lengths and relative abundance in a sample, based on digital amplification of individual template molecules. This invention has many applications, including those in noninvasive prenatal diagnosis, transplantation monitoring, and the detection and monitoring of cancers and virus-associated diseases.

    Type: Grant

    Filed: October 28, 2010

    Issued: May 13, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu

     

    Determining a nucleic acid sequence imbalance

    Patent number: 8706422

    Abstract: Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The cutoff value may also be determined based on an average concentration of a sequence per reaction. In one aspect, the cutoff value is determined from a proportion of informative wells that are estimated to contain a particular nucleic acid sequence, where the proportion is determined based on the above-mentioned percentage and/or average concentration. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing (NASDAQ:SPRT).

    Type: Grant

    Filed: July 23, 2008

    Issued: April 22, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Benny Chung Ying Zee, Ka Chun Chong

     

    MUTATIONAL ANALYSIS OF PLASMA DNA FOR CANCER DETECTION

    Application number: 20140100121

    Abstract: A frequency of somatic mutations in a biological sample (e.g., plasma or serum) of a subject undergoing screening or monitoring for cancer, can be compared with that in the constitutional DNA of the same subject. A parameter can derived from these frequencies and used to determine a classification of a level of cancer. False positives can be filtered out by requiring any variant locus to have at least a specified number of variant sequence reads (NYSEARCA:TAGS), thereby providing a more accurate parameter. The relative frequencies for different variant loci can be analyzed to determine a level of heterogeneity of tumors in a patient.

    Type: Application

    Filed: March 13, 2013

    Issued: April 10, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Peiyong Jiang

     

    FETAL GENOMIC ANALYSIS THAT ACCOUNTS FOR GC BIAS

    Application number: 20140080720

    Abstract: Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.

    Type: Application

    Filed: November 25, 2013

    Issued: March 20, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Wenli Zheng

     

    DETERMINING PERCENTAGE OF FETAL DNA IN MATERNAL SAMPLE

    Application number: 20140045181

    Abstract: Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The percentage of fetal DNA can be calculated from the same or different data used to determine the cutoff value, and can use a locus where the mother is homozygous and the fetus is heterozygous. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing .

    Type: Application

    Filed: September 18, 2013

    Issued: February 13, 2014

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan, Benny Chung-Ying Zee, Ka Chun Chong

     

    NONINVASIVE PRENATAL GENOTYPING OF FETAL SEX CHROMOSOMES

    Application number: 20140019064

    Abstract: Methods, apparatuses, and system are provided for analyzing a maternal sample to determine whether a male fetus of a pregnant female has inherited an X-linked mutation from the mother. A percentage of fetal DNA in the sample is obtained, and cutoff values for the two possibilities (fetus inherits mutant or normal allele) are determined. A proportion of mutant alleles relative to a normal allele on the X-chromosome can then be compared to the cutoff values to make a classification of which allele is inherited. Alternatively, a number of alleles from a target region on the X-chromosome can be compared to a number of alleles from a reference region on the X-chromosome to identify a deletion or amplification. The fetal DNA percentage can be computed by counting reactions with a fetal-specific allele, and correcting the number to account for a statistical distribution among the reactions.

    Type: Application

    Filed: January 5, 2012

    Issued: January 16, 2014

    Assignee: THE CHINESE UNIVERSITY OF HONG KONG

    Inventors: Yuk Ming Dennis Lo, Wai kwun Rossa Chiu, Kwan Chee Chan, Bo Yin Tsui

     

    Size-based genomic analysis

    Patent number: 8620593

    Abstract: Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.

    Type: Grant

    Filed: November 5, 2010

    Issued: December 31, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Wenli Zheng

     

    METHODS FOR DETECTING DNA PRIOGINATING FROM DIFFERENT INDIVIDUALS

    Application number: 20130337443

    Abstract: In a first aspect, the present invention features methods for differentiating DNA species originating from different individuals in a biological sample. These methods may be used to differentiate or detect fetal DNA in a maternal sample or to differentiate DNA of an organ donor from DNA of an organ recipient. In preferred embodiments, the DNA species are differentiated by observing epigenetic differences in the DNA species such as differences in DNA methylation. In a second aspect, the present invention features methods of detecting genetic abnormalities in a fetus by detecting fetal DNA in a biological sample obtained from a mother. In a third aspect, the present invention features methods for differentiating DNA species originating from an organ donor from those of an organ recipient. In a fourth aspect, the present invention features kits for differentiating DNA species originating from different individuals in a biological sample.

    Type: Application

    Filed: April 3, 2013

    Issued: December 19, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis LO, Lit Man Poon

     

    DETERMINATION OF THE DEPTH COVERAGE OF THE FETAL GENOME

    Application number: 20130323731

    Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.

    Type: Application

    Filed: May 15, 2013

    Issued: December 5, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Charles Cantor

     

    DIAGNOSING CANCER USING GENOMIC SEQUENCING

    Application number: 20130310263

    Abstract: Methods, systems, and apparatus determine whether a first chromosomal region exhibits a deletion or an amplification associated with cancer in a sample from a subject (e.g., where the sample includes a mixture of cell-free DNA from tumor cells and non-malignant cells. Nucleic acid molecules of the biological sample are sequenced. Respective amounts of a clinically-relevant chromosomal region and of background chromosomal region(s) are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether first chromosomal region exhibits a deletion or an amplification associated with cancer.

    Type: Application

    Filed: July 8, 2013

    Issued: November 21, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    Method for detecting chromosomal aneuploidy

    Patent number: 8563242

    Abstract: The present invention relates to a new, non-invasive method for detecting chromosomal aneuploidy by analyzing a sample from a pregnant woman. The detection is based on the ratio between the amount of a fetal methylation marker located on a chromosome relevant to the aneuploidy and the amount of a fetal genetic marker located on a reference chromosome, offering improved accuracy.

    Type: Grant

    Filed: July 9, 2010

    Issued: October 22, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu, Yu Kwan Tong, Shengnan Jin, Siu Chung Stephen Chim, Wai Yi Tsui

     

    NONINVASIVE PRENATAL DIAGNOSIS OF FETAL TRISOMY BY ALLELIC RATIO ANALYSIS USING TARGETED MASSIVELY PARALLEL SEQUENCING

    Application number: 20130267425

    Abstract: Whether a fetus has an aneuploidy associated with a first chromosome is detected using ratios of alleles detected in a maternal sample having a mixture of maternal and fetal DNA. DNA from the sample is enriched for target regions associated with polymorphic loci and then sequenced. Polymorphic loci (e.g., single nucleotide polymorphisms) in the target regions with fetal-specific alleles are identified on a first chromosome and on one or more reference chromosomes. A first ratio of the fetal-specific alleles and shared alleles is determined for the loci on the first chromosome. A second ratio of the fetal-specific alleles and shared alleles is determined for the loci on the reference chromosome(s). A third ratio of the first and second ratio can be compared to a cutoff to determine whether an aneuploidy is present, and whether the aneuploidy is maternally-derived or paternally-derived.

    Type: Application

    Filed: April 8, 2013

    Issued: October 10, 2013

    Assignee: THE CHINESE UNIVERSITY OF HONG KONG

    Inventors: Jiawei Liao, Kwan Chee Chan, Wai Kwun Rossa Chiu, Yuk Ming Dennis Lo

     

    IDENTIFYING A DE NOVO FETAL MUTATION FROM A MATERNAL BIOLOGICAL SAMPLE

    Application number: 20130253844

    Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.

    Type: Application

    Filed: May 15, 2013

    Issued: September 26, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Charles Cantor

     

    METHODS FOR ANALYZING MASSIVELY PARALLEL SEQUENCING DATA FOR NONINVASIVE PRENATAL DIAGNOSIS

    Application number: 20130245961

    Abstract: This invention provides several ways of managing GC bias that occurs during seequencing and analysis of genomic DNA. Maternal plasma can be used as a source of fetal DNA for analysis. DNA segments or tags obtained from the plasma can be aligned with a chromosomal region of interest and with an artificial reference chromosome assembled from regions of the genome having matching GC content.

    Type: Application

    Filed: March 13, 2013

    Issued: September 19, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Kwan Chee Chan, Wenli Zheng, Hao Sun, Zhang Chen

     

    SIZE-BASED ANALYSIS OF FETAL DNA FRACTION IN MATERNAL PLASMA

    Application number: 20130237431

    Abstract: A fractional concentration of clinically-relevant DNA in a mixture of DNA from a biological sample is determined based on amounts of DNA fragments at multiple sizes. For example, the fractional concentration of fetal DNA in maternal plasma or tumor DNA in a patient's plasma can be determined. The size of DNA fragments in a sample is shown to be correlated with a proportion of fetal DNA and a proportion of tumor DNA, respectively. Calibration data points (e.g., as a calibration function) indicate a correspondence between values of a size parameter and the fractional concentration of the clinically-relevant DNA. For a given sample, a first value of a size parameter can be determined from the sizes of DNA fragments in a sample. A comparison of the first value to the calibration data points can provide the estimate of the fractional concentration of the clinically-relevant DNA.

    Type: Application

    Filed: March 7, 2013

    Issued: September 12, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Kwan Chee Chan, Wenli Zheng, Peiyong Jiang, Jiawei Liao

     

    Fetal genomic analysis from a maternal biological sample

    Patent number: 8467976

    Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.

    Type: Grant

    Filed: November 5, 2010

    Issued: June 18, 2013

    Assignees: The Chinese University Of Hong Kong, Sequenom Inc.

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Charles Cantor

     

    Diagnosing fetal chromosomal aneuploidy using paired end

    Patent number: 8442774

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

    Type: Grant

    Filed: March 28, 2012

    Issued: May 14, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    Methods for detecting DNA originating from different individuals

    Patent number: 8431343

    Abstract: In a first aspect, the present invention features methods for differentiating DNA species originating from different individuals in a biological sample. These methods may be used to differentiate or detect fetal DNA in a maternal sample or to differentiate DNA of an organ donor from DNA of an organ recipient. In preferred embodiments, the DNA species are differentiated by observing epigenetic differences in the DNA species such as differences in DNA methylation. In a second aspect, the present invention features methods of detecting genetic abnormalities in a fetus by detecting fetal DNA in a biological sample obtained from a mother. In a third aspect, the present invention features methods for differentiating DNA species originating from an organ donor from those of an organ recipient. In a fourth aspect, the present invention features kits for differentiating DNA species originating from different individuals in a biological sample.

    Type: Grant

    Filed: April 2, 2012

    Issued: April 30, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Lit Man Poon

     

    FETAL METHYLATION MARKERS

    Application number: 20130084566

    Abstract: This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB2IP, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.

    Type: Application

    Filed: September 14, 2012

    Issued: April 4, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: YUK MING DENNIS LO, Rossa Wai Kwun Chiu, Stephen Siu Chung Chim, Chunming Ding, Kwan Chee Chan, Hing Nam Ivy Wong, Ka Chun Ryan Yuen

     

    MOLECULAR TESTING OF MULTIPLE PREGNANCIES

    Application number: 20130059733

    Abstract: Methods, systems, and apparatus are provided for determining zygosity of a multiple-fetus pregnancy using a biological sample taken from the mother. The fetal and maternal DNA in the sample (e.g. plasma) can be analyzed for a particular chromosomal region to identify genetic differences in the fetuses. For example, a normalized parameter for the measure of a primary or secondary allele can show variances for different chromosomal regions when fetuses are dizygotic. Such a variance can be determined relative to an expected value if the fetuses were genetically identical. Statistical methods are provided for analyzing the variation of the normalized parameters to determine fetal DNA concentration and the maternal-fetal mixed genotype at various loci. Parental genotype and haplotype information can also be used to identify inheritance of different parental haplotypes to indicate genetic differences among the fetuses.

    Type: Application

    Filed: February 24, 2012

    Issued: March 7, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Wai Kwun Rossa Chu, Kwan Chee Chan, Tak Yeung Leung, Peiyong Jiang

     

    DETECTION OF GENETIC OR MOLECULAR ABERRATIONS ASSOCIATED WITH CANCER

    Application number: 20130040824

    Abstract: Biological samples including cell-free DNA fragments are analyzed to identify imbalances in chromosomal regions, e.g., due to deletions and/or amplifications in a tumor. Multiple loci are used for each chromosomal region. Such imbalances can then be used to diagnose (screen) a patient for cancer, as well as prognosticate a patient with cancer, or to detect the presence or to monitor the progress of a premalignant condition in a patient. The severity of an imbalance as well as the number of regions exhibiting an imbalance can be used. A systematic analysis of non-overlapping segments of a genome can provide a general screening tool for a sample. Additionally, a patient can be tested over time to track severity of each of one or more chromosomal regions and a number of chromosomal regions to enable screening and prognosticating, as well as monitoring of progress (e.g. after treatment).

    Type: Application

    Filed: November 30, 2011

    Issued: February 14, 2013

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Peiyong Jiang

     

    Methods for detecting fetal DNA in a plasma or serum sample from a pregnant woman

    Patent number: 8288100

    Abstract: This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB2IP, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.

    Type: Grant

    Filed: June 1, 2010

    Issued: October 16, 2012

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu, Stephen Siu Chung Chim, Chunming Ding, Kwan Chee Chan, Hing Nam Ivy Wong, Ka Chun Ryan Yuen

     

    METHOD FOR NON-INVASIVE PRENATAL DIAGNOSIS

    Application number: 20120225798

    Abstract: The present invention is directed to methods of detecting nucleic acids in a biological sample. The method is based on a novel combination of a base extension reaction, which provides excellent analytical specificity, and a mass spectrometric analysis, which provides excellent specificity. The method can be used, for example, for diagnostic, prognostic and treatment purposes. The method allows accurate detection of nucleic acids that are present in very small amounts in a biological sample. For example, the method of the present invention is preferably used to detect fetal nucleic acid in a maternal blood sample; circulating tumor-specific nucleic acids in a blood, urine or stool sample; and donor-specific nucleic acids in transplant recipients. In another embodiment, one can detect viral, bacterial, fungal, or other foreign nucleic acids in a biological sample.

    Type: Application

    Filed: February 8, 2012

    Issued: September 6, 2012

    Assignee: THE TRUSTEES OF BOSTON UNIVERSITY

    Inventors: Charles R. Cantor, Chunming Ding, Yuk Ming Dennis Lo, Rossa Wai Kwum Chiu

     

    DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING MASSIVELY PARALLEL GENOMIC SEQUENCING

    Application number: 20120208708

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

    Type: Application

    Filed: March 9, 2012

    Issued: August 16, 2012

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING PAIRED END

    Application number: 20120190559

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

    Type: Application

    Filed: March 28, 2012

    Issued: July 26, 2012

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    Methods for detecting DNA originating from different individuals

    Patent number: 8168382

    Abstract: In a first aspect, the present invention features methods for differentiating DNA species originating from different individuals in a biological sample. These methods may be used to differentiate or detect fetal DNA in a maternal sample or to differentiate DNA of an organ donor from DNA of an organ recipient. In preferred embodiments, the DNA species are differentiated by observing epigenetic differences in the DNA species such as differences in DNA methylation. In a second aspect, the present invention features methods of detecting genetic abnormalities in a fetus by detecting fetal DNA in a biological sample obtained from a mother. In a third aspect, the present invention features methods for differentiating DNA species originating from an organ donor from those of an organ recipient. In a fourth aspect, the present invention features kits for differentiating DNA species originating from different individuals in a biological sample.

    Type: Grant

    Filed: October 13, 2008

    Issued: May 1, 2012

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Lit Man Poon

     

    Methods and kits for diagnosis, prognosis or monitoring of epstein-barr virus (EBV)-associated cancer

    Patent number: 8124383

    Abstract: Disclosed is a non-invasive method for diagnosis, prognosis or monitoring of Epstein-Barr virus (EBV)-associated cancer by detecting and/or quantifying EBV associated nucleic acid fragments in a urine sample from an individual. Kits for diagnosis, prognosis or monitoring of cancer are also disclosed.

    Type: Grant

    Filed: October 21, 2010

    Issued: February 28, 2012

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Allen Chan

     

    DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING MASSIVELY PARALLEL GENOMIC SEQUENCING

    Application number: 20120003635

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

    Type: Application

    Filed: March 23, 2011

    Issued: January 5, 2012

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING MASSIVELY PARALLEL GENOMIC SEQUENCING

    Application number: 20120003636

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

    Type: Application

    Filed: March 23, 2011

    Issued: January 5, 2012

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan-Chee Chan

     

    MARKER FOR PRENATAL DIAGNOSIS AND MONITORING

    Application number: 20120003650

    Abstract: The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status.

    Type: Application

    Filed: August 22, 2011

    Issued: January 5, 2012

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis LO, Rossa Wai Kwun Chiu, Stephen Siu Chung Chim, Yu-Kwan Tong, Chunming Ding

     

    DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING MASSIVELY PARALLEL GENOMIC SEQUENCING

    Application number: 20120003637

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

    Type: Application

    Filed: March 23, 2011

    Issued: January 5, 2012

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING MASSIVELY PARALLEL GENOMIC SEQUENCING

    Application number: 20110318734

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

    Type: Application

    Filed: March 23, 2011

    Issued: December 29, 2011

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    SIZE-BASED GENOMIC ANALYSIS

    Application number: 20110276277

    Abstract: Systems, methods, and apparatuses for performing a prenatal diagnosis of a sequence imbalance are provided. A shift (e.g. to a smaller size distribution) can signify an imbalance in certain circumstances. For example, a size distribution of fragments of nucleic acids from an at-risk chromosome can be used to determine a fetal chromosomal aneuploidy. A size ranking of different chromosomes can be used to determine changes of a rank of an at-risk chromosome from an expected ranking. Also, a difference between a statistical size value for one chromosome can be compared to a statistical size value of another chromosome to identify a significant shift in size. A genotype and haplotype of the fetus may also be determined using a size distribution to determine whether a sequence imbalance occurs in a maternal sample relative to a genotypes or haplotype of the mother, thereby providing a genotype or haplotype of the fetus.

    Type: Application

    Filed: November 5, 2010

    Issued: November 10, 2011

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Wenli Zheng

     

    Marker for prenatal diagnosis and monitoring

    Patent number: 8026067

    Abstract: The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status.

    Type: Grant

    Filed: March 15, 2010

    Issued: September 27, 2011

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu, Stephen Siu Chung Chim, Yu-kwan Tong, Chunming Ding

     

    Analysis for Nucleic Acids by Digital PCR

    Application number: 20110183330

    Abstract: The present invention provides a method for analyzing nucleic acids for their lengths and relative abundance in a sample, based on digital amplification of individual template molecules. This invention has many applications, including those in noninvasive prenatal diagnosis, transplantation monitoring, and the detection and monitoring of cancers and virus-associated diseases.

    Type: Application

    Filed: October 28, 2010

    Issued: July 28, 2011

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis LO, Rossa Wai Kwun Chiu

     

    NEW FETAL METHYLATION MARKERS

    Application number: 20110143342

    Abstract: This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB2IP, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.

    Type: Application

    Filed: June 1, 2010

    Issued: June 16, 2011

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu, Stephen Siu Chung Chim, Chunming Ding, Kwan Chee Chan, Hing Nam Ivy Wong, Ka Chun Ryan Yuen

     

    Fetal Genomic Analysis From A Maternal Biological Sample

    Application number: 20110105353

    Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.

    Type: Application

    Filed: November 5, 2010

    Issued: May 5, 2011

    Assignee: The Chinese University of Hong Kong c/o Technology Licensing Office

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Chan, Wai Kwun Rossa Chiu, Charles Cantor

     

    METHODS FOR ASSESSING LIVER PATHOLOGIES

    Application number: 20110098192

    Abstract: The present invention provides a new method for detecting or monitoring a liver disease in a subject that has no indication of any liver pathologies, by measuring the amount of concentration of albumin mRNA in an acellular blood sample from the subject, and then comparing the amount or concentration of albumin mRNA with a standard control.

    Type: Application

    Filed: September 10, 2010

    Issued: April 28, 2011

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu, Rebecca Wing Yan Chan

     

    Methods for Evaluating a Disease Condition by Nucleic Acid Detection and Fractionation

    Application number: 20110086357

    Abstract: This invention relates to the discovery that both non-particle and particle associated nucleic acids are present in blood plasma and serum and can be used to evaluate disease conditions.

    Type: Application

    Filed: November 8, 2010

    Issued: April 14, 2011

    Inventors: Yuk Ming Dennis Lo, Kai On Ng, Bo Yin Tsui, Wai Kwun Rossa Chiu, Yuen Shan Lisa Chan, Timothy Hudson Rainer, Yuk Lan Lam

     

    Markers for prenatal diagnosis and monitoring

    Patent number: 7901884

    Abstract: This application provides the use of novel fetal markers for prenatal diagnosis and monitoring of certain pregnancy-related conditions. More specifically, the invention resides in the discovery that certain CpG islands located on fetal chromosome 21 demonstrate a methylation profile that is distinct from that of the corresponding CpG islands located on maternal chromosome 21. This application also provides kits for diagnosing or monitoring of the relevant conditions.

    Type: Grant

    Filed: April 6, 2007

    Issued: March 8, 2011

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu, Stephen Siu Chung Chim, Chunming Ding, Shengnan Jin, Tracy Yuen Han Lee, Fiona Miu Fun Lun

     

    METHOD FOR DETECTING CHROMOSOMAL ANEUPLOIDY

    Application number: 20110039724

    Abstract: The present invention relates to a new, non-invasive method for detecting chromosomal aneuploidy by analyzing a sample from a pregnant woman. The detection is based on the ratio between the amount of a fetal methylation marker located on a chromosome relevant to the aneuploidy and the amount of a fetal genetic marker located on a reference chromosome, offering improved accuracy.

    Type: Application

    Filed: July 9, 2010

    Issued: February 17, 2011

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu, Yu Kwan Tong, Shengnan Jin, Siu Chung Stephen Chim, Wai Yi Tsui

     

    METHODS AND KITS FOR DIAGNOSIS, PROGNOSIS OR MONITORING OF EPSTEIN-BARR VIRUS (EBV)-ASSOCIATED CANCER

    Application number: 20110033841

    Abstract: Disclosed is a non-invasive method for diagnosis, prognosis or monitoring of Epstein-Barr virus (EBV)-associated cancer by detecting and/or quantifying EBV associated nucleic acid fragments in a urine sample from an individual. Kits for diagnosis, prognosis or monitoring of cancer are also disclosed.

    Type: Application

    Filed: October 21, 2010

    Issued: February 10, 2011

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Allen Chan

     

    Marker for Prenatal Diagnosis and Monitoring

    Application number: 20100323352

    Abstract: The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status.

    Type: Application

    Filed: March 15, 2010

    Issued: December 23, 2010

    Assignee: THE CHINESE UNIVERSITY OF HONG KONG

    Inventors: YUK MING DENNIS LO, ROSSA WAI KWUN CHIU, STEPHEN SIU CHUNG CHIM, YU-KWAN TONG, CHUNMING DING

     

    METHOD FOR THE DETECTION OF CHROMOSOMAL ANEUPLOIDIES

    Application number: 20100311046

    Abstract: The non-invasive detection of fetal chromosomal aneuploidies is demonstrated. Alleles of fetal RNA-SNPs present in a biological sample (e.g. maternal blood) containing fetal RNA are detected and quantified in order to determine the ratio of the alleles. This ratio is compared to a standard control consisting of euploid fetuses. Deviation of allele ratio indicates the presence of chromosomal aneuploidy.

    Type: Application

    Filed: November 16, 2009

    Issued: December 9, 2010

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Bo Yin Tsui, Chunming Ding, Charles Cantor

     

    Methods and kits for diagnosis, prognosis or monitoring of Epstein-Barr virus (EBV)-associated cancer

    Patent number: 7842482

    Abstract: Disclosed is a non-invasive method for diagnosis, prognosis or monitoring of Epstein-Barr virus (EBV)-associated cancer by detecting and/or quantifying EBV associated nucleic acid fragments in a urine sample from an individual. Kits for diagnosis, prognosis or monitoring of cancer are also disclosed.

    Type: Grant

    Filed: February 26, 2007

    Issued: November 30, 2010

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Allen Chan

     

    Circulating mRNA as diagnostic markers

    Patent number: 7829285

    Abstract: Methods and kits are provided for diagnosing, monitoring, or predicting the conditions of pre-eclampsia, fetal chromosomal aneuploidy, and pre-term labor in a pregnant woman, as well as for detecting pregnancy in a woman, by quantitatively measuring in the maternal blood the amount of one or more mRNA species encoding human chorionic gonadotropin ? subunit (hCG-?), human placental lactogen (hPL), human corticotropin releasing hormone (hCRH), KiSS-1 metastasis-suppressor (KISS1), tissue factor pathway inhibitor 2 (TPFI2), placenta-specific 1 (PLAC1), or glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and comparing the amount of the mRNA species with a standard control.

    Type: Grant

    Filed: May 24, 2007

    Issued: November 9, 2010

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Kai On Ng, Bo Yin Tsui, Wai Kwun Rossa Chiu

     

    MARKERS FOR PRENATAL DIAGNOSIS AND MONITORING

    Application number: 20100267034

    Abstract: Methods and kits are provided for diagnosing, monitoring, or predicting preeclaimpsia in a pregnant woman, trisomy 18 and trisomy 21 in a fetus, as well as for detecting pregnancy in a woman, by quantitatively measuring in the maternal blood the amount of one or more RNA species derived from a set of genetic loci and comparing the amount of the RNA species with a standard control.

    Type: Application

    Filed: April 5, 2010

    Issued: October 21, 2010

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis LO, Rossa Wai Kwun CHIU, Stephen Siu Chung CHIM, Nancy Bo Yin TSUI

     

    Fetal methylation markers

    Patent number: 7754428

    Abstract: This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB2IP, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.

    Type: Grant

    Filed: April 6, 2007

    Issued: July 13, 2010

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu, Stephen Siu Chung Chim, Chunming Ding, Kwan Chee Chan, Hing Nam Ivy Wong, Ka Chun Ryan Yuen

     

    Markers for prenatal diagnosis and monitoring

    Patent number: 7718367

    Abstract: Methods and kits are provided for diagnosing, monitoring, or predicting preeclaimpsia in a pregnant woman, trisomy 18 and trisomy 21 in a fetus, as well as for detecting pregnancy in a woman, by quantitatively measuring in the maternal blood the amount of one or more RNA species derived from a set of genetic loci and comparing the amount of the RNA species with a standard control.

    Type: Grant

    Filed: March 17, 2006

    Issued: May 18, 2010

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Stephen Siu Chung Chim, Nancy Bo Yin Tsui

     

    Diagnosing Fetal Chromosomal Aneuploidy Using Genomic Sequencing With Enrichment

    Application number: 20100112590

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. The determination of the relative amounts may count sequences of only certain length. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists. Prior to sequencing, the biological sample may be enriched for DNA fragments of a particular sizes.

    Type: Application

    Filed: November 6, 2009

    Issued: May 6, 2010

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    Marker for prenatal diagnosis and monitoring

    Patent number: 7709194

    Abstract: The present invention relates to new methods for diagnosing a pregnancy-associated disorder by analyzing fetal DNA present in the mother's blood. More specifically, this invention relies on the discovery that the maspin gene is differentially methylated in fetal DNA and in maternal DNA and provides these new diagnostic methods, which distinguish fetal DNA from maternal DNA and detect prenatal disorders based on abnormalities in fetal DNA level and methylation status.

    Type: Grant

    Filed: June 3, 2005

    Issued: May 4, 2010

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu, Stephen Siu Chung Chim, Yu-kwan Tong, Chunming Ding

     

    Method for the detection of chromosomal aneuploidies

    Patent number: 7645576

    Abstract: The non-invasive detection of fetal chromosomal aneuploidies is demonstrated. Alleles of fetal RNA-SNPs present in a biological sample (e.g. maternal blood) containing fetal RNA are detected and quantified in order to determine the ratio of the alleles. This ratio is compared to a standard control consisting of euploid fetuses. Deviation of allele ratio indicates the presence of chromosomal aneuploidy.

    Type: Grant

    Filed: March 17, 2006

    Issued: January 12, 2010

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Bo Yin Tsui, Chunming Ding, Charles Cantor

     

    METHODS FOR DETECTING DNA ORIGINATING FROM DIFFERENT INDIVIDUALS

    Application number: 20090170102

    Abstract: In a first aspect, the present invention features methods for differentiating DNA species originating from different individuals in a biological sample. These methods may be used to differentiate or detect fetal DNA in a maternal sample or to differentiate DNA of an organ donor from DNA of an organ recipient. In preferred embodiments, the DNA species are differentiated by observing epigenetic differences in the DNA species such as differences in DNA methylation. In a second aspect, the present invention features methods of detecting genetic abnormalities in a fetus by detecting fetal DNA in a biological sample obtained from a mother. In a third aspect, the present invention features methods for differentiating DNA species originating from an organ donor from those of an organ recipient. In a fourth aspect, the present invention features kits for differentiating DNA species originating from different individuals in a biological sample.

    Type: Application

    Filed: October 13, 2008

    Issued: July 2, 2009

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis LO, Lit Man Poon

     

    Circulating mRNA as diagnostic markers

    Application number: 20090162842

    Abstract: Methods and kits are provided for diagnosing, monitoring, or predicting the conditions of pre-eclampsia, fetal chromosomal aneuploidy, and pre-term labor in a pregnant woman, as well as for detecting pregnancy in a woman, by quantitatively measuring in the maternal blood the amount of one or more mRNA species encoding human chorionic gonadotropin ? subunit (hCG-?), human placental lactogen (hPL), human corticotropin releasing hormone (hCRH), KiSS-1 metastasis-suppressor (KISS1), tissue factor pathway inhibitor 2 (TPFI2), placenta-specific 1 (PLAC1), or glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and comparing the amount of the mRNA species with a standard control.

    Type: Application

    Filed: May 24, 2007

    Issued: June 25, 2009

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Kai On Ng, Bo Yin Tsui, Wai Kwun Chiu

     

    Fetal methylation markers

    Application number: 20090155776

    Abstract: This application describes the discovery that, in a pregnant woman, certain genes (such as RASSF1A, APC, CASP8, RARB, SCGB3A1, DAB2IP, PTPN6, THY1, TMEFF2, and PYCARD) originated from a fetus are highly methylated, whereas the same genes of maternal origin are unmethylated. This discovery allows the easy detection of one or more of these methylated fetal genes in a biological sample from a pregnant woman, serving as a universal indicator of the presence of fetal DNA in the sample. These fetal methylation markers are particularly useful as positive controls for a non-invasive analytical process during which the quality and quantity of fetal DNA are monitored. These newly identified fetal markers can also be measured directly for diagnosis of certain pregnancy-related conditions.

    Type: Application

    Filed: April 6, 2007

    Issued: June 18, 2009

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun Chiu, Stephen Siu Chung Chim, Chunming Ding, Kwan Chee Chan, Hing Nam Ivy Wong, Ka Chun Ryan Yuen

     

    DETERMINING A NUCLEIC ACID SEQUENCE IMBALANCE

    Application number: 20090087847

    Abstract: Methods, systems, and apparatus are provided for determining whether a nucleic acid sequence imbalance exists within a biological sample. One or more cutoff values for determining an imbalance of, for example, the ratio of the two sequences (or sets of sequences) are chosen. The cutoff value may be determined based at least in part on the percentage of fetal DNA in a sample, such as maternal plasma, containing a background of maternal nucleic acid sequences. The cutoff value may also be determined based on an average concentration of a sequence per reaction. In one aspect, the cutoff value is determined from a proportion of informative wells that are estimated to contain a particular nucleic acid sequence, where the proportion is determined based on the above-mentioned percentage and/or average concentration. The cutoff value may be determined using many different types of methods, such as sequential probability ratio testing .

    Type: Application

    Filed: July 23, 2008

    Issued: April 2, 2009

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis LO, Rossa Wai Kwun Chiu, Kwan Chee Chan, Benny Chung Ying Zee, Ka Chun Chong

     

    Methods and kits for selectively amplifying, detecting or quantifying target DNA with specific end sequences

    Application number: 20090061425

    Abstract: Disclosed herein are methods and kits for selectively amplifying, detecting or quantifying a DNA fragment with a specific end sequence, especially generated following restriction enzyme digestion. This method can be used, for example, to detect a hypomethylated DNA fragment. This methods and kits are especially useful in detecting or quantifying a hypomethylated fetal DNA fragment in a maternal plasma sample containing a corresponding hypermethylated maternal DNA fragment.

    Type: Application

    Filed: August 30, 2007

    Issued: March 5, 2009

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Yu Kwan Tong, Wai Kwun Rossa Chiu, Chunming Ding

     

    ANALYSIS OF NUCLEIC ACIDS BY DIGITAL PCR

    Application number: 20090053719

    Abstract: The present invention provides a method for analyzing nucleic acids for their lengths and relative abundance in a sample, based on digital amplification of individual template molecules. This invention has many applications, including those in noninvasive prenatal diagnosis, transplantation monitoring, and the detection and monitoring of cancers and virus-associated diseases.

    Type: Application

    Filed: July 31, 2008

    Issued: February 26, 2009

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Rossa Wai Kwun CHIU

     

    DIAGNOSING FETAL CHROMOSOMAL ANEUPLOIDY USING MASSIVELY PARALLEL GENOMIC SEQUENCING

    Application number: 20090029377

    Abstract: Embodiments of this invention provide methods, systems, and apparatus for determining whether a fetal chromosomal aneuploidy exists from a biological sample obtained from a pregnant female. Nucleic acid molecules of the biological sample are sequenced, such that a fraction of the genome is sequenced. Respective amounts of a clinically-relevant chromosome and of background chromosomes are determined from results of the sequencing. A parameter derived from these amounts (e.g. a ratio) is compared to one or more cutoff values, thereby determining a classification of whether a fetal chromosomal aneuploidy exists.

    Type: Application

    Filed: July 23, 2008

    Issued: January 29, 2009

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Rossa Wai Kwun Chiu, Kwan Chee Chan

     

    COMPOSITIONS AND METHODS FOR DIAGNOSING AND TREATING SEVERE ACUTE RESPIRATORY SYNDROME (SARS)

    Application number: 20080286756

    Abstract: The present invention relates to the fields of immunochemistry and pharmacology. Methods and compositions are described for the diagnosis and treatment of SARS CoV infection. More specifically, the application discloses nucleic acids and peptides of the spike glycoprotein of SARS CoV that provide prognostic and therapeutic compositions in treatment of individuals contracting, or in danger of contracting SARS CoV. The peptides of the invention are also useful in producing antibodies against the SARS CoV glycoprotein.

    Type: Application

    Filed: April 3, 2008

    Issued: November 20, 2008

    Assignee: THE CHINESE UNIVERSITY OF HONG KONG

    Inventors: Kwok Wing TSUI, Kwok Pui Fung, Mary Miu Yee Waye, Yuk Ming Dennis Lo, Siu Chung Stephen Chim, Wai Kwun Rossa Chiu, Siu Lun John Tam, Kay Sheung Paul Chan

     

    Methods and kits for diagnosis, prognosis or monitoring of Epstein-Barr virus (EBV)-associated cancer

    Application number: 20080206749

    Abstract: Disclosed is a non-invasive method for diagnosis, prognosis or monitoring of Epstein-Barr virus (EBV)-associated cancer by detecting and/or quantifying EBV associated nucleic acid fragments in a urine sample from an individual. Kits for diagnosis, prognosis or monitoring of cancer are also disclosed.

    Type: Application

    Filed: February 26, 2007

    Issued: August 28, 2008

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kwan Chee Allen Chan

     

    Circulating mRNA as diagnostic markers

    Application number: 20080153090

    Abstract: Methods and kits are provided for diagnosing, monitoring, or predicting the conditions of pre-eclaimpsia, fetal chromosomal aneuploidy, and pre-term labor in a pregnant woman, as well as for detecting pregnancy in a woman, by quantitatively measuring in the maternal blood the amount of one or more mRNA species encoding human chorionic gonadotropin ? subunit (hCG-?), human placental lactogen (hPL), human corticotropin releasing hormone (hCRH), KiSS-1 metastasis-suppressor (KISS1), tissue factor pathway inhibitor 2 (TPFI2), placenta-specific 1 (PLAC1), or glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and comparing the amount of the mRNA species with a standard control.

    Type: Application

    Filed: May 24, 2007

    Issued: June 26, 2008

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Kai On Ng, Bo Yin Tsui, Wai Kwun Rossa Chiu

     

    Compositions and methods for diagnosing and treating severe acute respiratory syndrome (SARS)

    Patent number: 7371525

    Abstract: The present invention relates to the fields of immunochemistry and pharmacology. Methods and compositions are described for the diagnosis and treatment of SARS CoV infection. More specifically, the application discloses nucleic acids and peptides of the spike glycoprotein of SARS CoV that provide prognostic and therapeutic compositions in treatment of individuals contracting, or in danger of contracting SARS CoV. The peptides of the invention are also useful in producing antibodies against the SARS CoV glycoprotein.

    Type: Grant

    Filed: July 28, 2004

    Issued: May 13, 2008

    Assignee: The Chinese University of Hong Kong

    Inventors: Kwok Wing Tsui, Siu Chung Stephen Chim, Mary Miu Yee Waye, Kwok Pui Fung, Yuk Ming Dennis Lo, Wai Kwun Rossa Chiu, Siu Lun John Tam, Kay Sheung Paul Chan

     

    Method for diagnosing preeclampsia by detecting hCRH mRNA

    Patent number: 7235359

    Abstract: Methods and kits are provided for diagnosing, monitoring, or predicting the conditions of pre-eclaimpsia, fetal chromosomal aneuploidy, and pre-term labor in a pregnant woman, as well as for detecting pregnancy in a woman, by quantitatively measuring in the maternal blood the amount of one or more mRNA species encoding human chorionic gonadotropin ? subunit (hCG-?), human placental lactogen (hPL), human corticotropin releasing hormone (hCRH), KiSS-1 metastasis-suppressor (KISS1), tissue factor pathway inhibitor 2 (TPFI2), placenta-specific 1 (PLAC1), or glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and comparing the amount of the mRNA species with a standard control.

    Type: Grant

    Filed: January 16, 2004

    Issued: June 26, 2007

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Kai On Ng, Bo Yin Tsui, Wai Kwun Rossa Chiu

     

    Methods for evaluating stroke or cardiac ischemia by nucleic acid detection

    Patent number: 7022478

    Abstract: This invention relates to the use of a blood sample from a patient for evaluating stroke or cardiac ischemia in the patient.

    Type: Grant

    Filed: July 11, 2002

    Issued: April 4, 2006

    Assignee: The Chinese University of Hong Kong

    Inventors: Timothy Hudson Rainer, Yuk Ming Dennis Lo, Yuk Lan Lam, Lawrence Ka Sing Wong

     

    Circulating mRNA as diagnostic markers

    Application number: 20040203037

    Abstract: Methods and kits are provided for diagnosing, monitoring, or predicting the conditions of pre-eclaimpsia, fetal chromosomal aneuploidy, and pre-term labor in a pregnant woman, as well as for detecting pregnancy in a woman, by quantitatively measuring in the maternal blood the amount of one or more mRNA species encoding human chorionic gonadotropin &bgr; subunit (hCG-&bgr;), human placental lactogen (hPL), human corticotropin releasing hormone (hCRH), KiSS-1 metastasis-suppressor (KISS1), tissue factor pathway inhibitor 2 (TPFI2), placenta-specific 1 (PLAC1), or glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and comparing the amount of the mRNA species with a standard control.

    Type: Application

    Filed: January 16, 2004

    Issued: October 14, 2004

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk-Ming Dennis Lo, Kai On Ng, Bo Yin Tsui, Wai Kwun Rossa Chiu

     

    Circulating epstein-barr virus DNA in the serum of patients with gastric carcinoma

    Patent number: 6753137

    Abstract: The present invention features methods for diagnosing, detecting, monitoring and determining the prognosis of gastric cancer, non-head and neck and lymphoid malignancies, and gastritis in a patient by detecting or measuring EBV DNA present in the serum or plasma of the patient. The present invention also features diagnostic kits comprising suitable reagents for detecting EBV DNA in the serum or plasma of a patient.

    Type: Grant

    Filed: January 25, 2002

    Issued: June 22, 2004

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Wing Yee Chan, Kwok Wai Ng

     

    Novel classification methods for pleural effusions

    Application number: 20040086864

    Abstract: This invention relates to the detection of nucleic acids in the pleural fluids of a patient suffering from a pleural effusion for the classification of the pleural effusion.

    Type: Application

    Filed: October 22, 2002

    Issued: May 6, 2004

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Michael Ho-Ming Chan

     

    Methods for evaluating a disease condition by nucleic acid detection and fractionation

    Application number: 20040009518

    Abstract: This invention relates to the discovery that both non-particle and particle associated nucleic acids are present in blood plasma and serum and can be used to evaluate disease conditions.

    Type: Application

    Filed: May 13, 2003

    Issued: January 15, 2004

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Kai On Ng, Bo Yin Tsui, Wai Kwun Rossa Chiu, Yuen Shan Lisa Chan, Timothy Hudson Rainer, Yuk Lan Lam

     

    Circulating epstein-barr virus DNA in the serum or plasma of patients for the prediction and detection of epstein-barr virus associated cancers apart from head, neck and lymphoid malignancies

    Application number: 20040005551

    Abstract: The present invention features methods for diagnosing, detecting, monitoring and determining the prognosis of Epstein Barr virus associated cancers apart from head, neck and lymphoid malignancies in a patient by detecting or measuring EBV DNA present in the serum or plasma of the patient. The present invention also features diagnostic kits comprising suitable reagents for detecting EBV DNA in the serum or plasma of a patient.

    Type: Application

    Filed: June 3, 2003

    Issued: January 8, 2004

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Wing Yee Chan, Kwok Wai Ng

     

    Non-invasive prenatal monitoring

    Patent number: 6664056

    Abstract: Embodiments of the present invention are directed to the detection of fetal or maternal RNA in a blood sample from a pregnant subject, and may involve subjecting the sample to a test for fetal or maternal analysis indicative of a fetal or maternal condition or characteristics. For instance, the RNA analysis may involve the assessment of the gene expression pattern of an unborn fetus by analyzing a blood sample from the mother. The prenatal monitoring technology allows, for the first time, the detection of genes which are expressed by the fetus, just by analysis of a sample of maternal blood. In specific embodiments, the prenatal monitoring technology is based on the discovery of circulating RNA of fetal origin in the plasma of pregnant women. In general, the detection method performed on a maternal serum or plasma sample from a pregnant female comprises detecting the presence of RNA of fetal or maternal original in the sample.

    Type: Grant

    Filed: June 6, 2001

    Issued: December 16, 2003

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Lit Man Poon

     

    Combination of circulating epstein-barr virus (EBV) DNA in the serum or plasma of patients and a method to assess EBV subtypes for the prediction and detection of epstein-barr virus associated cancers

    Application number: 20030228575

    Abstract: The present invention features methods for diagnosing, detecting, monitoring and determining the prognosis of Epstein Barr virus associated cancers in a patient by detecting or measuring EBV DNA present in the serum or plasma of the patient followed by EBV subtyping of polymorphisms. The sensitivity of the circulating EBV DNA serves as a good screening tool while the EBV subtyping of polymorphism confirms the prognosis or diagnosis of EBV associated malignancies. The present invention also features diagnostic kits comprising suitable reagents for the above tests.

    Type: Application

    Filed: August 8, 2003

    Issued: December 11, 2003

    Assignees: Yuk Ming Dennis Lo, The Chinese University of Hong Kong

    Inventors: Wah Hin Alex Yeung, Yuk Ming Dennis Lo

     

    Methods for evaluating stroke or cardiac ischemia by nucleic acid detection

    Application number: 20030219759

    Abstract: This invention relates to the use of a blood sample from a patient for evaluating stroke or cardiac ischemia in the patient.

    Type: Application

    Filed: July 11, 2002

    Issued: November 27, 2003

    Assignee: The Chinese University of Hong Kong

    Inventors: Timothy Hudson Rainer, Yuk Ming Dennis Lo, Yuk Lan Lam, Lawrence Ka Sing Wong

     

    Circulating epstein-barr virus DNA in the serum of patients with gastric carcinoma

    Application number: 20020192642

    Abstract: The present invention features methods for diagnosing, detecting, monitoring and determining the prognosis of gastric cancer, non-head and neck and lymphoid malignancies, and gastritis in a patient by detecting or measuring EBV DNA present in the serum or plasma of the patient. The present invention also features diagnostic kits comprising suitable reagents for detecting EBV DNA in the serum or plasma of a patient.

    Type: Application

    Filed: January 25, 2002

    Issued: December 19, 2002

    Assignee: The Chinese University of Hong Kong

    Inventors: Yuk Ming Dennis Lo, Wing Yee Chan, Kwok Wai Ng

     

    Non-invasive prenatal monitoring

    Application number: 20020045176

    Abstract: Embodiments of the present invention are directed to the detection of fetal or maternal RNA in a blood sample from a pregnant subject, and may involve subjecting the sample to a test for fetal or maternal analysis indicative of a fetal or maternal condition or characteristics. For instance, the RNA analysis may involve the assessment of the gene expression pattern of an unborn fetus by analyzing a blood sample from the mother. The prenatal monitoring technology allows, for the first time, the detection of genes which are expressed by the fetus, just by analysis of a sample of maternal blood. In specific embodiments, the prenatal monitoring technology is based on the discovery of circulating RNA of fetal origin in the plasma of pregnant women. In general, the detection method performed on a maternal serum or plasma sample from a pregnant female comprises detecting the presence of RNA of fetal or maternal original in the sample.

    Type: Application

    Filed: June 6, 2001

    Issued: April 18, 2002

    Inventors: Yuk Ming Dennis Lo, Lit Man Poon

     

    Non-invasive prenatal diagnosis

    Application number: 20010051341

    Abstract: The invention relates to a detection method performed on a maternal serum or plasma from a pregnant female, which method comprises the presence of a nucleic acid of fetal origin in the sample. The invention enables non-invasive prenatal diagnosis including, for example, sex determination, blood typing and other genotyping, and detection of pre-eclampsia in the mother.

    Type: Application

    Filed: June 1, 2001

    Issued: December 13, 2001

    Assignee: ISIS Innovation Limited

    Inventors: Yuk-Ming Dennis Lo, James Stephen Wainscoat

     

    Non-invasive prenatal diagnosis

    Patent number: 6258540

    Abstract: The invention relates to a detection method performed on a maternal serum or plasma sample from a pregnant female, which method comprises detecting the presence of a nucleic acid of foetal origin in the sample. The invention enables non-invasive prenatal diagnosis including for example sex determination, blood typing and other genotyping, and detection of pre-eclampsia in the mother.

    Type: Grant

    Filed: November 29, 1999

    Issued: July 10, 2001

    Assignee: Isis Innovation Limited

    Inventors: Yuk-Ming Dennis Lo, James Stephen Wainscoat

    Jul 30 1:38 PM | Link | Comment!
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