Sequenom

Last updated

Sequenom, Inc.
Company type Subsidiary
NYSE: SQNM (2000–2016)
Industry Biotechnology
Founded1 January 1994  OOjs UI icon edit-ltr-progressive.svg
Headquarters,
US
Key people
Dirk van den Boom (CEO)
ProductsMaterniT21 PLUS, MaterniT GENOME, VisibiliT, HerediT CF, HerediT UNIVERSAL, NextView, SensiGene RHD
ServicesNon-Invasive Prenatal Testing (NIPT), Carrier Screening
Parent LabCorp (2016–present)
Website www.sequenom.com

Sequenom, Inc. is an American company based in San Diego, California. It develops enabling molecular technologies, and highly sensitive laboratory genetic tests for NIPT. Sequenom's wholly owned subsidiary, Sequenom Center for Molecular Medicine (SCMM), offers multiple clinical molecular genetics tests to patients, including MaterniT21, plus a noninvasive prenatal test for trisomy 21, trisomy 18, and trisomy 13, and the SensiGene RHD Fetal RHD genotyping test.

Contents

The company went public via an initial public offering in 2000. [1] In June 2014 the company sold its biosciences unit to Agena Bioscience for up to $35.8 million. [2] In July 2016, it was announced that diagnostic and testing giant LabCorp will acquire Sequenom, paying $2.40 for every outstanding share of Sequenom stock. The acquisition was completed in September 2016. [3]

Competition

Companies also offering non-invasive prenatal genetic testing include Ariosa, [4] Ravgen, [5] Illumina (Verinata Health), [6] PerkinElmer and Natera (The Panorama Prenatal Test). [7] Other companies and universities that are working towards developing non-invasive prenatal testing include Stanford University. [8]

Patent litigation

In January 2012, Sequenom entered a patent battle with competing companies, Ariosa and Natera, accusing them of infringing the "540 patent" ( US 6258540  ). [9] The cases are Sequenom Inc. v. Natera Inc. 12-cv-0184, Sequenom v. Ariosa Diagnostics Inc., 12-cv-0189, U.S. District Court, Southern District of California (San Diego), and Ariosa v. Sequenom.

Verinatal Health and Stanford University later filed suit against Sequenom in a dispute over the 'Quake patent'. Verinata claims that Sequenom's lawyers sent it a letter in 2010 alleging that "'the practice of non-invasive prenatal diagnostics, including diagnosis of the Down Syndrome and other genetic disorders, using cell-free nucleic acids in a sample of maternal blood infringes' the '540 patent, as well as the claims of a pending United States Patent Application." [10] The '540 patent was invented by Isis Ltd. and expires in 2017.

Stanford University owns the Quake patents and licensing rights; Verinata is its exclusive licensee. [10]

In April 2012, Sequenom acquired two pending patents from Helicos Biosciences. In consideration for the sale and transfer of the purchased assets, Sequenom paid Helicos $1.3 million. The Helicos patent applications (US Patent application 12/709,057 and 12/727,824) cover methods for detecting fetal nucleic acids and diagnosing fetal abnormalities. [11]

In July 2012, The United States District Court denied Sequenom's motion for a preliminary injunction motion against Ariosa Diagnostics. [12]

In August 2013, The Court of Appeals for the Federal Circuit vacated the District Court decision and remanded that case to the District Court. [13]

In the Ariosa litigation, the District Court (N.D.Cal.) held that the '540 patent was invalid because it claimed a natural phenomenon, the presence of cell-free fetal DNA fragments in maternal blood. On June 13, 2015, the CAFC affirmed the District Court's judgment. [14] Finally, on December 2, 2015, the Federal Circuit declined to rehear en banc . [15]

SEQureDx scandal

In 2009, Sequenom Center for Molecular Medicine (SCMM) was expected to launch the SEQureDx prenatal screening tests for Down syndrome and Rhesus D. Subsequent investigation revealed significant flaws in the studies of the test's effectiveness. [16] As a result, the board of directors of Sequenom fired CEO Harry Stylli, senior vice president of research and development Elizabeth Dragon and three other employees after a probe discovered that the company had failed to adequately supervise its Down syndrome test. CFO Paul Hawran also resigned. Board chairman Harry F. Hixson Jr. was named interim CEO and director Ronald M. Lindsay was appointed to replace Dragon. Dragon has since been charged by the Securities and Exchange Commission (SEC) because she "lied to the public about the accuracy of Sequenom's prenatal screening test for Down syndrome". [17] She died on February 26, 2011. [18] [19]

In 2010, Sequenom paid $14 million to settle a shareholder class-action lawsuit that arose from the errors in the development of the Down syndrome test. [20] Sequenom executives are under investigation by the SEC for insider trading before announcement of problems with the test. [21] [22]

On September 1, 2011, Sequenom entered into a cease-and-desist order with SEC. [23]

MaterniT21 PLUS

MaterniT21 PLUS is Sequenom Center for Molecular Medicine's prenatal test for trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome). The test operates by sampling cell-free DNA in the mother's blood, which contains some DNA from the fetus. The proportions of DNA from sequences from chromosome 21, 18, or 13 can indicate whether the fetus has trisomy in that chromosome. In a randomized controlled trial of 1,696 pregnancies at high risk for Down syndrome, the test correctly identified 98.6% of the actual cases of Down syndrome (209 out of 212), with a false positive rate of 0.2% (3 of 1471 pregnancies without Down); the test gave no result in 0.8% of the cases tested (13 of 1696). [24]

The primary advantage of MaterniT21 PLUS over the other major high accuracy tests for Down syndrome, Amniocentesis and Chorionic villus sampling, is that MaterniT21 PLUS is noninvasive. [24] Because amniocentesis and chorionic villus sampling are invasive, they have a chance of causing miscarriage. [25]

History

On August 4, 2011, Sequenom said it would call its new blood test for Down syndrome in pregnancy MaterniT21 when the product went on sale in the United States. [26] [27] [28] [29]

On August 11, 2011, Sequenom announced a European licensing agreement with LifeCodexx. The companies agreed to collaborate in the development and launch of a trisomy 21 laboratory-developed test and other aneuploidies testing in Germany, Austria, Switzerland, and Liechtenstein, with the potential for additional launches in other countries. Under the initial five year licensing agreement, Sequenom granted LifeCodexx licenses to key patent rights, including European Patent EP0994963B1 and pending application EP2183693A1 that enable the development and commercialization of a non-invasive aneuploidy test utilizing circulating cell-free fetal DNA in maternal plasma. [30]

On October 24, 2011 International Society of Prenatal Diagnostics (ISPD) issued a rapid response statement in response to the launch of Sequenom non-invasive Trisomy 21 (MaterniT21) test. [31]

On October 17, 2011 Sequenom announced that a clinical validation study leading to the introduction of the MaterniT21 LDT had been published in the journal Genetics in Medicine. [32] On October 17, 2011 Sequenom Center for Molecular Medicine announced the launch of MaterniT21 Noninvasive Prenatal Test for Down Syndrome. [29]

MassARRAY Analyzer 4

Sequenom Oncomap Version 3 – "core" set interrogates ~450 mutations in 35 genes. An "extended" set interrogates ~700 mutations in 113 genes. [33]

Sequenom OncoCarta(OncoMap) identifies 396 unique "druggable" or "actionable" mutations in 33 cancer genes. In total, 417 mutations are identified. [34] [35] [36] [37]

MassARRAY spectrometry is more sensitive than PreTect HPV-Proofer and Consensus PCR for type-specific detection of high-risk oncogenic human papillomavirus genotypes in cervical cancer. [38]

iPLEX ADME PGx Panel on MassARRAY System

On October 4, 2011 Sequenom introduced iPLEX ADME PGx Panel on MassARRAY System, developed to genotype polymorphisms in genes associated with drug absorption, distribution, metabolism, and excretion (ADME). This Research Use Only (RUO) panel contains a set of pre-designed single nucleotide polymorphisms (SNP), insertions and deletions (INDELS) and copy number variation (CNV) assays for use in the investigation of variants with demonstrated relevance to drug metabolism. After detection on the MassARRAY (RUO) system, a proprietary software solution is then used to score and qualify polymorphisms to create a unique haplotype report. [39]

Related Research Articles

<span class="mw-page-title-main">Down syndrome</span> Genetic disorder

Down syndrome or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is usually associated with developmental delays, mild to moderate intellectual disability, and characteristic physical features. There are three types of Down syndrome, all with the same features: Trisomy 21, the most common type; Mosaic Down syndrome, and Translocation Down syndrome.

<span class="mw-page-title-main">Amniocentesis</span> Sampling of amniotic fluid done mainly to detect fetal chromosomal abnormalities

Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is necessary to conclusively diagnose the majority of genetic disorders, with amniocentesis being the gold-standard procedure after 15 weeks' gestation.

<span class="mw-page-title-main">Genetic testing</span> Medical test

Genetic testing, also known as DNA testing, is used to identify changes in DNA sequence or chromosome structure. Genetic testing can also include measuring the results of genetic changes, such as RNA analysis as an output of gene expression, or through biochemical analysis to measure specific protein output. In a medical setting, genetic testing can be used to diagnose or rule out suspected genetic disorders, predict risks for specific conditions, or gain information that can be used to customize medical treatments based on an individual's genetic makeup. Genetic testing can also be used to determine biological relatives, such as a child's biological parentage through DNA paternity testing, or be used to broadly predict an individual's ancestry. Genetic testing of plants and animals can be used for similar reasons as in humans, to gain information used for selective breeding, or for efforts to boost genetic diversity in endangered populations.

<span class="mw-page-title-main">Prenatal testing</span> Testing for diseases or conditions in a fetus

Prenatal testing is a tool that can be used to detect some birth defects at various stages prior to birth. Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health of the zygote, embryo, or fetus, either before gestation even starts or as early in gestation as practicable. Screening can detect problems such as neural tube defects, chromosome abnormalities, and gene mutations that would lead to genetic disorders and birth defects, such as spina bifida, cleft palate, Down syndrome, trisomy 18, Tay–Sachs disease, sickle cell anemia, thalassemia, cystic fibrosis, muscular dystrophy, and fragile X syndrome. Some tests are designed to discover problems which primarily affect the health of the mother, such as PAPP-A to detect pre-eclampsia or glucose tolerance tests to diagnose gestational diabetes. Screening can also detect anatomical defects such as hydrocephalus, anencephaly, heart defects, and amniotic band syndrome.

The triple test, also called triple screen, the Kettering test or the Bart's test, is an investigation performed during pregnancy in the second trimester to classify a patient as either high-risk or low-risk for chromosomal abnormalities.

The Pallister–Killian syndrome (PKS), also termed tetrasomy 12p mosaicism or the Pallister mosaic aneuploidy syndrome, is an extremely rare and severe genetic disorder. PKS is due to the presence of an extra and abnormal chromosome termed a small supernumerary marker chromosome (sSMC). sSMCs contain copies of genetic material from parts of virtually any other chromosome and, depending on the genetic material they carry, can cause various genetic disorders and neoplasms. The sSMC in PKS consists of multiple copies of the short arm of chromosome 12. Consequently, the multiple copies of the genetic material in the sSMC plus the two copies of this genetic material in the two normal chromosome 12's are overexpressed and thereby cause the syndrome. Due to a form of genetic mosaicism, however, individuals with PKS differ in the tissue distributions of their sSMC and therefore show different syndrome-related birth defects and disease severities. For example, individuals with the sSMC in their heart tissue are likely to have cardiac structural abnormalities while those without this sSMC localization have a structurally normal heart.

<span class="mw-page-title-main">Nuchal scan</span> Routine ultrasound done between 11 and 14 weeks pregnancy

A nuchal scan or nuchal translucency (NT) scan/procedure is a sonographic prenatal screening scan (ultrasound) to detect chromosomal abnormalities in a fetus, though altered extracellular matrix composition and limited lymphatic drainage can also be detected.

Noninvasive genotyping is a modern technique for obtaining DNA for genotyping that is characterized by the indirect sampling of specimen, not requiring harm to, handling of, or even the presence of the organism of interest. Beginning in the early 1990s, with the advent of PCR, researchers have been able to obtain high-quality DNA samples from small quantities of hair, feathers, scales, or excrement. These noninvasive samples are an improvement over older allozyme and DNA sampling techniques that often required larger samples of tissue or the destruction of the studied organism. Noninvasive genotyping is widely utilized in conservation efforts, where capture and sampling may be difficult or disruptive to behavior. Additionally, in medicine, this technique is being applied in humans for the diagnosis of genetic disease and early detection of tumors. In this context, invasivity takes on a separate definition where noninvasive sampling also includes simple blood samples.

<span class="mw-page-title-main">Trisomy 16</span> Partial or complete triplication of chromosome 16

Trisomy 16 is a chromosomal abnormality in which there are 3 copies of chromosome 16 rather than two. It is the most common trisomy leading to miscarriage and the second most common chromosomal cause of it, closely following X-chromosome monosomy. About 6% of miscarriages have trisomy 16. Those mostly occur between 8 and 15 weeks after the last menstrual period.

Prenatal sex discernment is the prenatal testing for discerning the sex of a fetus before birth.

Ravgen Inc. is a privately owned biotech company founded by Chairman and C.E.O. Dr. Ravinder Dhallan. Ravgen Inc. is known for its research in the prenatal diagnostic field and its development of non-invasive prenatal diagnosis testing which was published in The Lancet, the Journal of the American Medical Association ., and the New England Journal of Medicine. These publications received worldwide press in The Times, The Washington Post, CNN Fortune Small Business, and The New York Times

Ravinder (Rav) Dhallan is the chairman and chief executive officer of Ravgen.

Natera, Inc. is a clinical genetic testing company based in Austin, Texas that specializes in non-invasive, cell-free DNA (cfDNA) testing technology, with a focus on women’s health, cancer, and organ health. Natera’s proprietary technology combines novel molecular biology techniques with a suite of bioinformatics software that allows detection down to a single molecule in a tube of blood. Natera operates CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in San Carlos, California and Austin, Texas.

Cell-free fetal DNA (cffDNA) is fetal DNA that circulates freely in the maternal blood. Maternal blood is sampled by venipuncture. Analysis of cffDNA is a method of non-invasive prenatal diagnosis frequently ordered for pregnant women of advanced maternal age. Two hours after delivery, cffDNA is no longer detectable in maternal blood.

<span class="mw-page-title-main">Molecular diagnostics</span> Collection of techniques used to analyze biological markers in the genome and proteome

Molecular diagnostics is a collection of techniques used to analyze biological markers in the genome and proteome, and how their cells express their genes as proteins, applying molecular biology to medical testing. In medicine the technique is used to diagnose and monitor disease, detect risk, and decide which therapies will work best for individual patients, and in agricultural biosecurity similarly to monitor crop- and livestock disease, estimate risk, and decide what quarantine measures must be taken.

Dennis Yuk Ming Lo is a Hong Kong molecular biologist, and an important contributor to the development of non-invasive prenatal testing. He is the current Associate Dean (Research) and Li Ka Shing Professor of Medicine at the Chinese University of Hong Kong (CUHK), as well as the head of the Department of Chemical Pathology of CUHK and the director of the Li Ka Shing Institute of Health Sciences. His research focuses on the detection of cell-free fetal DNA in blood plasma.

<span class="mw-page-title-main">Diana W. Bianchi</span> American medical geneticist and neonatologist

Diana W. Bianchi is the director of the U.S. National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development, a post often called “the nation’s pediatrician.” She is a medical geneticist and neonatologist noted for her research on fetal cell microchimerism and prenatal testing. Bianchi had previously been the Natalie V. Zucker Professor of Pediatrics, Obstetrics, and Gynecology at Tufts University School of Medicine and founder and executive director of the Mother Infant Research Institute at Tufts Medical Center. She also has served as Vice Chair for Research in the Department of Pediatrics at the Floating Hospital for Children at Tufts Medical Center.

Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, is a controversial decision of the Federal Circuit in which the court applied the Mayo v. Prometheus test to invalidate as patent-ineligible a patent said to "solve ... a very practical problem accessing fetal DNA without creating a major health risk for the unborn child." The rationale for denying patent-eligibility in this case allegedly stems from claims being directed toward non-eligible subject matter , "if the APPLICATION [of this discovery] merely relies upon elements already known in the art."

Noninvasive prenatal testing (NIPT) is a method used to determine the risk for the fetus being born with certain chromosomal abnormalities, such as trisomy 21, trisomy 18 and trisomy 13. This testing analyzes small DNA fragments that circulate in the blood of a pregnant woman. Unlike most DNA found in the nucleus of a cell, these fragments are not found within the cells, instead they are free-floating, and so are called cell free fetal DNA (cffDNA). These fragments usually contain less than 200 DNA building blocks and arise when cells die, and their contents, including DNA, are released into the bloodstream. cffDNA derives from placental cells and is usually identical to fetal DNA. Analysis of cffDNA from placenta provides the opportunity for early detection of certain chromosomal abnormalities without harming the fetus.

Dame Lyn Susan Chitty is a British physician and Professor of Genetics and Fetal Medicine at University College London. She is the deputy director of the National Institute for Health and Care Research Great Ormond Street Hospital Biomedical Research Centre. She is the 2022 president of the International Society for Prenatal Diagnosis. Her research considers non-invasive prenatal diagnostics. She was made a Dame in the 2022 New Year Honours.

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