Claims for Patent: 8,592,149

Summary for Patent: 8,592,149

Title:	Methods and compositions for antibody therapy
Abstract:	Methods and materials are provided for determining the responsiveness of a subject to a therapy, such as an antibody therapy and for selecting and/or for treating a subject based on a Fc.gamma.RIIA polymorphism, or a Fc.gamma.RIIIA polymorphism, or both an Fc.gamma.RIIA polymorphism and a Fc.gamma.RIIIA polymorphism, including where the treatment is an therapy, such as rituximab. Methods and materials are also provided for designing, making, screening, testing and/or administering antibodies as well as for optimizing antibody therapies based upon a subject\'s Fc.gamma.RIIA polymorphism, or Fc.gamma.RIIIA polymorphism, or both the Fc.gamma.RIIA polymorphism and the Fc.gamma.RIIIA polymorphism.
Inventor(s):	Ramakrishnan; Vijay (Palo Alto, CA)
Assignee:	PIKAMAB, Inc. (Palo Alto, CA)
Application Number:	12/298,661
Patent Claims:	1. A method for generating a reference index which correlates treatment response to nine Fc.gamma.RIIIa and Fc.gamma.RIIa genotype groups, said method comprising: (a) genotyping multiple human subjects, each subject has or had an ADCC-treatable disease or disorder, and is or was administered antibody therapy for said disease or disorder resulting in a treatment response; said genotyping classifies said subject into one of nine genotype groups corresponding to V/V.sup.158 and H/H.sup.131, designated group I; V/F.sup.158 and H/H.sup.131, designated group II; F/F.sup.158 and H/H.sup.131, designated group III; V/V.sup.158 and H/R.sup.131, designated group IV; V/F.sup.158 and H/R.sup.131, designated group V; F/F.sup.158 and H/R.sup.131, designated group VI; V/V.sup.158 and R/R.sup.131, designated group VII; V/F.sup.158 and R/R.sup.131, designated group VIII; and F/F.sup.158 and R/R.sup.131, designated group IX; and (b) further classifying said treatment response of each subject based on its Fc.gamma.RIIIa V/F.sup.158 and Fc.gamma.RIIa H/R.sup.131 genotype groups to generate a reference index which correlates said nine categories of treatment response with said nine genotype groups. 2. A method for classifying a human test subject having said ADCC-treatable disease or disorder into a category of treatment response to said antibody therapy, said method comprising: a) genotyping said test subject to classify into one of nine genotype groups corresponding to V/V.sup.158 and H/H.sup.131, designated group I; V/F.sup.158 and H/H.sup.131, designated group II; F/F.sup.158 and H/H.sup.131, designated group III; V/V.sup.158 and H/R.sup.131, designated group IV; V/F.sup.158 and H/R.sup.131, designated group V; F/F.sup.158 and H/R.sup.131, designated group VI; V/V.sup.158 and R/R.sup.131, designated group VII; V/F.sup.158 and R/R.sup.131, designated group VIII; and F/F.sup.158 and R/R.sup.131, designated group IX; and b) classifying said test subject using said genotype group into a category of treatment response which is indicated from said reference index of claim 1. 3. The method of claim 2, wherein: a) said category of treatment response is a component of a treatment decision; or b) said category of treatment response is a component of a decision not to treat with said antibody therapy; or c) said test subject is treated with said antibody therapy. 4. The method of claim 1, wherein said subject was administered antibody therapy in the past. 5. The method of claim 1, wherein said ADCC-treatable disease or disorder is a neoplastic disease or disorder. 6. The method of claim 1, wherein said ADCC-treatable disease or disorder is an autoimmune disease or disorder. 7. The method of claim 1, wherein said antibody therapy comprised administration of an anti-CD20 antibody. 8. The method of claim 1, wherein said antibody therapy comprised treatment with an antibody selected from the group consisting of rituximab, alemtuzumab, daclizumab, trastuzumab, omalizumab, efalizumab, bevacizumab, infliximab, adalimumab, cetuximab, basiliximab, palivizumab, panitumumab, natalizumab, gemtuzumab ozogamicin, abciximab, ranibizumab, eculizumab, muromonab-CD3, tositumomab and ibritumomab tiuxetan. 9. A method for predicting treatment response to an antibody therapy for a human test subject having an ADCC-treatable disease or disorder, said method comprising: a) classifying said test subject into one of nine genotype groups corresponding to V/V.sup.158 and H/H.sup.131, designated group I; V/F.sup.158 and H/H.sup.131, designated group II; F/F.sup.158 and H/H.sup.131, designated group III; V/V.sup.158 and H/R.sup.131, designated group IV; V/F.sup.158 and H/R.sup.131, designated group V; F/F.sup.158 and H/R.sup.131, designated group VI; V/V.sup.158 and R/R.sup.131, designated group VII; V/F.sup.158 and R/R.sup.131, designated group VIII; and F/F.sup.158 and R/R.sup.131, designated group IX; and b) using a reference index that correlates nine categories of treatment response upon treatment with an antibody therapy with said genotype groups, thereby providing a prediction of treatment response for said test subject. 10. The method of claim 9, further including a step of genotyping said test subject by evaluating a biological sample by hybridization for classifying said subject into one of said nine genotype groups. 11. The method of claim 9 wherein a) said predicting of treatment response is a component of a treatment decision; or b) said predicting of treatment response is a component of a decision not to treat with said antibody therapy; or c) said test subject is treated with said antibody therapy. 12. A method for selecting a genotype group for a particular treatment with an antibody therapy for human test subjects having an ADCC-treatable disease or condition, said method comprising: a) using a reference index which correlates categories of treatment responses, said categories numbering more than three, and said categories corresponding to a single or combination of genotype groups, with said genotype group corresponding to V/V.sup.158 and H/H.sup.131, designated group I; V/F.sup.158 and H/H.sup.131, designated group II; F/F.sup.158 and H/H.sup.131, designated group III; V/V.sup.158 and H/R.sup.131, designated group IV; V/F.sup.158 and H/R.sup.131, designated group V; F/F.sup.158 and H/R.sup.131, designated group VI; V/V.sup.158 and R/R.sup.131, designated group VII; V/F.sup.158 and R/R.sup.131, designated group VIII; and F/F.sup.158 and R/R.sup.131, designated group IX; and b) selecting said genotype group(s) corresponding to a particular category of treatment response. 13. The method of claim 12, wherein said method identifies a particular test subject for said treatment, where said subject is in said genotype group corresponding to said category of treatment response. 14. The method of claim 12, wherein said method identifies a particular test subject for said treatment who is treated with said antibody therapy. 15. The method of claim 12, wherein said category of treatment response is a component of a decision not to treat with said antibody therapy. 16. The method of claim 12, wherein said genotype group corresponds to group IX. 17. A method for generating a reference index which correlates treatment response to Fc.gamma.RIIIa and Fc.gamma.RIIa genotype groups, said method comprising: (a) genotyping multiple human subjects, each subject has or had an ADCC-treatable disease or disorder, and is or was administered antibody therapy for said disease or disorder resulting in a treatment response; said genotyping classifies said subject into one of nine genotype groups corresponding to V/V.sup.158 and H/H.sup.131, designated group I; V/F.sup.158 and H/H.sup.131, designated group II; F/F.sup.158 and H/H.sup.131, designated group III; V/V.sup.158 and H/R.sup.131, designated group IV; V/F.sup.158 and H/R.sup.131, designated group V; F/F.sup.158 and H/R.sup.131, designated group VI; V/V.sup.158 and R/R.sup.131, designated group VII; V/F.sup.158 and R/R.sup.131, designated group VIII; and F/F.sup.158 and R/R.sup.131, designated group IX; and (b) further classifying said treatment response of each subject based on its Fc.gamma.RIIIa V/F.sup.158 and Fc.gamma.RIIa H/R.sup.131 genotype groups, wherein two or more genotype groups are combined to one category of treatment response to generate a reference index which contains more than three categories of treatment response. 18. A method for classifying a human test subject having said ADCC-treatable disease or disorder into a category of treatment response to said antibody therapy, said method comprising: a) genotyping said test subject into one of nine genotype groups corresponding to V/V.sup.158 and H/H.sup.131, designated group I; V/F.sup.158 and H/H.sup.131, designated group II; F/F.sup.158 and H/H.sup.131, designated group III; V/V.sup.158 and H/R.sup.131, designated group IV; V/F.sup.158 and H/R.sup.131, designated group V; F/F.sup.158 and H/R.sup.131, designated group VI; V/V.sup.158 and R/R.sup.131, designated group VII; V/F.sup.158 and R/R.sup.131, designated group VIII; and F/F.sup.158 and R/R.sup.131, designated group IX; and b) classifying said test subject using said genotype group into a category of treatment response which is indicated from said reference index of claim 17. 19. The method of claim 18, wherein said categories of treatment response number more than three, and one category corresponds to genotype: group I alone; group V alone; group IX alone; groups I, II, Ill, IV, and VII together; groups II and III together; groups IV and VII together; groups V, VI, VIII, and IX together; groups I, II, and III together; groups IV, V, and VI together; groups VII, VIII, and IX together; groups I, IV, and VII together; groups II, V, and VIII together; or groups III, VI, and IX together. 20. The method of claim 18, wherein a) said category of treatment response is a component of a treatment decision; b) said category of treatment response is a component of a decision not to treat with said antibody therapy; or c) said test subject is treated with said antibody therapy. 21. A method for selecting a genotype group for a particular treatment with an antibody therapy for human test subjects having an ADCC-treatable disease or condition, said method comprising: a) using a reference index which correlates categories of treatment responses, each category corresponding to treatment response to a single genotype group, with said genotype groups corresponding to V/V.sup.158 and H/H.sup.131, designated group I; V/F.sup.158 and H/H.sup.131, designated group II; F/F.sup.158 and H/H.sup.131, designated group III; V/V.sup.158 and H/R.sup.131, designated group IV; V/F.sup.158 and H/R.sup.131, designated group V; F/F.sup.158 and H/R.sup.131, designated group VI; V/V.sup.158 and R/R.sup.131, designated group VII; V/F.sup.158 and R/R.sup.131, designated group VIII; and F/F.sup.158 and R/R.sup.131, designated group IX; and b) selecting said genotype group corresponding to a particular category of treatment response. 22. The method of claim 21, wherein said method identifies a particular test subject for said treatment, where said subject is in said genotype group corresponding to said category of treatment response. 23. The method of claim 21, wherein said method identifies a particular test subject for said treatment who is treated with said antibody therapy. 24. The method of claim 21, wherein said category of treatment response is a component of a decision not to treat with said antibody therapy. 25. The method of claim 21, wherein said genotype group corresponds to group IX. 26. A method for predicting treatment response to an antibody therapy for a human test subject having an ADCC-treatable disease or disorder, said method comprising: a) classifying said test subject into one of nine genotype groups corresponding to V/V.sup.158 and H/H.sup.131, designated group I; V/F.sup.158 and H/H.sup.131, designated group II; F/F.sup.158 and H/H.sup.131, designated group III; V/V.sup.158 and H/R.sup.131, designated group IV; V/F.sup.158 and H/R.sup.131, designated group V; F/F.sup.158 and H/R.sup.131, designated group VI; V/V.sup.158 and R/R.sup.131, designated group VII; V/F.sup.158 and R/R.sup.131, designated group VIII; and F/F.sup.158 and R/R.sup.131, designated group IX; and b) using a reference index, said reference index containing more than three categories of treatment response, each corresponding to one or more genotype groups, which correlates category of treatment response to said genotype groups. 27. The method of claim 26, wherein: a) said category of treatment response is a component of a treatment decision; or b) said category of treatment response is a component of a decision not to treat with said antibody therapy; or c) said test subject is treated with said antibody therapy. 28. The method of claim 26, further including a step of genotyping said test subject by evaluating a biological sample by hybridization for classifying said subject into one of said nine genotype groups. 29. The method of claim 26, wherein said reference index has nine categories of treatment response, each category corresponding to a single genotype group. 30. The method of claim 26, wherein said categories of responsiveness include at least one category which corresponds to: group I alone; group V alone; group IX alone; groups I, II, Ill, IV, and VII together; groups II and III together; groups IV and VII together; groups V, VI, VIII, and IX together; groups I, II, and III together; groups IV, V, and VI together; groups VII, VIII, and IX together; groups I, IV, and VII together; groups II, V, and VIII together; or groups III, VI, and IX together. 31. The method of claim 26, wherein said ADCC-treatable disease or disorder is a neoplastic disease or disorder. 32. The method of claim 26, wherein said ADCC-treatable disease or disorder is an autoimmune disease or disorder. 33. The method of claim 26, wherein said antibody therapy is administration of an anti-CD20 antibody. 34. The method of claim 26, wherein said antibody therapy is treatment with an antibody selected from the group consisting of rituximab, alemtuzumab, daclizumab, trastuzumab, omalizumab, efalizumab, bevacizumab, infliximab, adalimumab, cetuximab, basiliximab, palivizumab, panitumumab, natalizumab, gemtuzumab ozogamicin, abciximab, ranibizumab, eculizumab, muromonab-CD3, tositumomab and ibritumomab tiuxetan. 35. A method of selecting an antibody therapy for human subjects having an ADCC-treatable disease, said antibodies in a set of two or more antibody therapies, said method comprising: a) classifying said subjects into nine genotype groups corresponding to V/V.sup.158 and H/H.sup.131, designated group I; V/F.sup.158 and H/H.sup.131, designated group II; F/F.sup.158 and H/H.sup.131, designated group III; V/V.sup.158 and H/R.sup.131, designated group IV; V/F.sup.158 and H/R.sup.131, designated group V; F/F.sup.158 and H/R.sup.131, designated group VI; V/V.sup.158 and R/R.sup.131, designated group VII; V/F.sup.158 and R/R.sup.131, designated group VIII; and F/F.sup.158 and R/R.sup.131, designated group IX; and b) comparing said genotypes to reference indices which correlate said genotype groups with corresponding categories of treatment response upon antibody therapy, each of said categories of treatment response corresponding to one or more genotype groups; and c) selecting a preferred antibody therapy for a particular genotype group where the degree of treatment response is improved compared to those other antibody therapies. 36. The method of claim 35, wherein a test subject has said particular genotype group, and that preferred antibody therapy is selected for that test subject. 37. The method of claim 35, wherein a test subject has said particular genotype group, and that preferred antibody therapy is selected for that test subject, and said test subject is treated with said preferred antibody therapy. 38. The method of claim 35, wherein said antibodies share antigen binding specificity. 39. The method of claim 35, wherein said antibodies differ in ability to mediate ADCC, phagocytosis or opsonization effector cell function. 40. The method of claim 35, wherein at least one of said reference indices has nine categories of treatment response.

Details for Patent 8,592,149

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Centocor Ortho Biotech Products, L.p.	ORTHOCLONE OKT3	muromanab-cd3	Injection	103463	09/14/1992		2026-04-27
Janssen Biotech, Inc.	REOPRO	abciximab	Injection	103575	12/22/1994		2026-04-27
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2026-04-27
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2026-04-27
Hoffmann-la Roche Inc.	ZENAPAX	daclizumab	Injection	103749	12/10/1997		2026-04-27