Statin patent applications
Details of the various applications with some observations by me in italics. You really get a good feel for the relative strength of the applications by the length and content of them, and I have to say that DNAP's looks to me to be in a different ballpark to the others.
IHC Health Services, Inc.
US Patent Application: 20020164598
Title: Method for evaluating and applying an individual's genetic characteristics to determine response to cardiovascular medication therapy
Filed: May 3, 2001
Last Update: November 7, 2002
A process for evaluating the genetic sensitivity of individual patients to medications and to appropriately prescribing or not prescribing medication according to established correlations between the genetic sensitivity and the specific medication is described. In the present preferred embodiment/example, this invention provides a process for determining whether a person, having either cardiovascular disease or cardiovascular risk factors, has a genetic characteristic which would indicate whether the ordinarily prescribed statin medication is likely to be effective or even detrimental.
It is desirable to provide a method for predicting the performance and applicability of drug and other medication treatment for patients with specific medical conditions. It is particularly desirable that such a method be based on the application of a genetic test, which provides for the detection of one or more genotypes, the presence of which can be used as a predictor of therapeutic response. In its present preferred embodiment, this invention makes use of the CETP Taq 1B Genotype as a predictor of therapeutic response to statin therapy in patients with severe coronary artery disease.
Note: single gene only (one of the ones Genaissance is working on).
Cedars-Sinai's Medical Genetics-Birth Defects Center
US Patent Application: 20020106657
Title: Genetic test to determine non-responsiveness to statin drug treatment
Filed: July 3, 2001
Last Update: August 8, 2002
The present invention relates to a method of detecting a genetic predisposition in a human subject for non-responsiveness to statin drug treatment for coronary artery disease. This genetic testing method involves analyzing amplification products of the nucleic acids in a human tissue sample that includes a non-coding or untranslated region within the 3' end of the human LPL gene. Homozygosity for a variant allele in a non-coding or untranslated region within the 3' end of the human LPL gene indicates a genetic predisposition for non-responsiveness to treatment with statin-class drugs, such as lovastatin, pravastatin, simvastatin, atorvastatin, fluvastatin, and cerivastatin, which are typically prescribed to treat atherosclerotic stenosis in subjects with coronary artery disease, or to prevent graft worsening (stenosis) in CABG patients.
Note: single gene only testing for non-responsiveness
DNAPrint Genomics
US Patent Application: 20030215819
Title: Compositions and methods for inferring a response to statin
Filed: July 1, 2002
Last Update: November 20, 2003
The present invention relates to compositions and methods useful for inferring a statin response of a subject from a nucleic acid sample of the subject. The invention is based, in part, on a determination that single nucleotide polymorphisms (SNPs), including haploid or diploid SNPs, and haplotype alleles (i.e., combinations of two or more SNPs in a single gene, e.g., a cytochrome P450 gene and/or a 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR) gene), including haploid or diploid haplotype alleles, allows an inference to be drawn as to whether a subject, particularly a human subject, will have a positive response to treatment with a statin, for example, by exhibiting a decrease in total cholesterol or in low density lipoprotein levels, or will have an adverse response, for example, liver damage. The statin can be any statin, including, for example, Atorvastatin or Simvastatin.
The results of this SNP screen are shown in Table 9-13. From Table 9-13 it is evident that many different genes impact variable Statin response. For most of the outcomes, there were SNPs from at least four different genes associated. It is also clear that the gene compliments are highly unique for each end point and each gene. The GSTs (GSTM1, GSTT2, GSTA2) were quite strongly associated with LIPITOR response, linked with LDL, TC and SGOT outcome, but not ZOCOR response. The NAT2 gene was only found to be relevant for ZOCOR response, and only had impact on the TC lowering effect of the drug, not the LDL lowering effect. CYP2C8 was an important determinant for both LIPITOR and ZOCOR, for the former, impacting both TC and SGOT outcome. Of significant interest, no SNPs, or only weakly associated SNPs in the HMGCS1, MVK or HMGCR gene were identified, though we previously described HMGCR haplotypes associated with response. Usually, the ability to identify associations at the level of the SNP indicates the gene contribution towards response is relatively strong compared to genes with associations only apparent at the level of the haplotype. The HMGCS 1, MVK and HMGCR genes are part of the cholesterol synthesis pathway inhibited by Statins, yet our results suggest that most of Statin variable response is attributed by xenobiotic metabolism gene sequences, not target pathway sequences. The associations we have described earlier in this application therefore are a function of haplotype, not SNP sequences. With these haplotypes, and SNPs from genes below, a linear or quadratic discriminate classifier (as we have described elsewhere, (T. Frudakis, U.S. patent application Ser. No. 10/156,995, filed May 28, 2002), Frudakis et al., J. Forensic Science, (2002); Frudakis 2002a) is possible to predict each outcome.
Note: Multiple genes testing for whether there will be a positive response or an adverse response for any of the statin class of drugs (different methods are included for each statin).
Genaissance
Poster presented at the 52nd Annual American College of Cardiology Scientific Session, March 30 - April 2, 2003
We discovered 179 SNPs including 30 novel, non-synomymous SNPs in ABCA1. We found a significant association between an ABCA1 haplotype marker and LDL-C reduction by statin treatment (P<0.0001). The association is also seen in the individual statin groups with p-values ranging from 0.04 to 0.003. The marker includes GLU(1192) ASP plus 4 other SNPs. Patients with >1 copy of the marker respond with 10% less LDL-C reduction than those without the marker. There were no differences in baseline lipids or HDL-C response between individuals based on this marker.
The fact that variability in drug response is determined by a disease pathway gene, and not by the drug target, is also significant. This finding suggests that a candidate gene approach to pharmacogenetics is dependent upon the
inclusion of genes in the disease pathway, as well as those in the target pathway. Indeed, this approach is essential even when mechanism of action is poorly understood, as is the case with statins.
Note: single gene, and different conclusion to that highlighted in the DNAP patent applicaiton.
Genaissance Pharmaceuticals Describes Link Between Genetic Markers and Drug Response in Cardiovascular Disease
— Clinical Data Support DNA-Based Diagnostic Tests to Enhance Treatment and Dosing Decisions for Cardiovascular Indications —
Orlando, FL, November 11, 2003 – Genaissance Pharmaceuticals, Inc. (Nasdaq: GNSC) today presented, at the American Heart Association's Scientific Sessions 2003, clinical data describing associations between genetic markers (HAP™ Markers) and response to treatment with the statin class of drugs. The two presentations provided additional results from Genaissance's Statin Response Examined by Genetic Haplotype Markers (STRENGTH) clinical study.
In one presentation, Genaissance confirmed an association between HAP™ Markers in the gene apolipoprotein E (ApoE) and levels of C-reactive protein (CRP), which has been associated with inflammation and linked to risk for arteriosclerosis. Genaissance also extended the association by identifying ApoE HAP™ Markers that are present in those patients who showed the greatest reduction in the level of CRP when treated with a statin.
"We believe that this finding could help predict which patients will experience the greatest anti-inflammation effect of statins, further reducing their risk for arteriosclerosis," said Richard S. Judson, Ph.D., Senior Vice President and Chief Scientific Officer of Genaissance Pharmaceuticals. "Our new findings, combined with our previously released data, provide the basis for new DNA-based diagnostic tests for the cardiovascular market that could be used to help physicians make dosing and other treatment decisions."
In the second presentation, Genaissance described an association between HAP™ Markers in the gene P-Selectin, which has been associated with diabetes and cardiovascular conditions, and changes in the level of HDL-Cholesterol (HDL-C) in response to statin therapy. The association was observed with all of the statins studied (atorvastatin, pravastatin and simvastatin) and represents an effect of the statin class of drugs. The HAP™ Markers also identified patients most likely to experience a reduction in HDL-C if switched to a higher dose of a statin.
"Having a high level of HDL-C is considered to be beneficial to one's health," said Dr. Judson. "We believe that genetic markers, such as those for P-Selectin, could aid a physician in treating a patient with the statin class of drugs so as to maximize the lowering of LDL-C, the bad cholesterol, while maintaining as high a level as possible of the good cholesterol, HDL-C."
WIPO Patent Application: WO 04/003167
Title: GUCY1B2 GENETIC MARKERS FOR LDL CHOLESTEROL RESPONSE TO STATIN THERAPY
Filed: June 28, 2002
Last Update: January 8, 2004
Genetic markers in the GUCY1B2 gene associated with LDL cholesterol response to treatment with atorvastatin calcium are disclosed. Compositions and methods for detecting and using these GUCY1B2 genetic markers in a variety of clinical applications are disclosed. Such applications include articles of manufacture comprising a statin composition approved for treating patients having one of these GUCY1B2 haplotypes, methods and kits for predicting the response of an individual to a given statin treatment based on their haplotype profile, and methods for treating individuals with hyperlipidemia based on their haplotype profile.
Note: single gene for atorvastatin only.
WIPO Patent Application: WO 03/091698
Title: CETP GENETIC MARKERS FOR STATIN-SPECIFIC CHANGES IN HDL CHOLESTEROL
Filed: April 28, 2003
Last Update: November 6, 2003
Genetic markers in the CETP gene associated with statin-specific changes in HDL cholesterol after statin treatment are disclosed. Compositions and methods for detecting and using these CETP genetic markers in a variety of clinical applications are disclosed. Such applications include articles of manufacture comprising a statin composition approved for treating patients having one of these CETP haplotypes, methods and kits for predicting the response of an individual to a given statin treatment based on their haplotype profile, and methods for treating individuals with hyperlipidemia based on their haplotype profile.
Note: single gene only.
Bayer
WIPO Patent Application: WO 03/072813
Title: SINGLE NUCLEOTIDE POLYMORPHISMS PREDICTING ADVERSE DRUG REACTIONS AND MEDICATION EFFICACY
Filed: February 14, 2003
Last Update: September 4, 2003
The invention provides diagnostic methods and kits including oligo and/or polynucleotides or derivatives, including as well antibodies determining whether a human subject is at risk of getting adverse drug reaction after statin therapy or whether the human subject is a high or low responder or a good a or bad metabolizer of statins. The invention provides further diagnostic methods and kits including antibodies determining whether a human subject is at risk for a cardiovascular disease. Still further the invention provides polymorphic sequences and other genes. The present invention further relates to isolated polynucleotides encoding a phenotype associated (PA) gene polypeptide useful in methods to identify therapeutic agents and useful for preparation of a medicament to treat cardiovascular disease or influence drug response, the polynucleotide is selected from the group comprising:SEQ ID 1-80 with allelic variation as indicated in the sequences section contained in a functional surrounding like full length cDNA for PA gene polypeptide and with or without the PA gene promoter sequence.
Note: single gene only.
AI
