DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Applicant’s amendments to the claims of March 9, 2026, in response to the Office Action of September 8, 2025, are acknowledged.
Response to Arguments
Applicant has narrowed the claims to require a subject to have FSGS rather than merely be capable of having FSGS. A new reference has been added below to address this. Applicant arguments are also addressed below in their entirety.
Applicant argues that the Hodges reference treat Alport syndrome through collagen replacement by administration of recombinant collagen IV protein. Applicant also argues that Hodges teaches using clopidogrel primarily to prevent thrombosis secondary to collagen replacement therapy.
The examiner notes that Cravedi indicates that FSGS is a glomerular disease characterized by proteinuria and frequent progression to end-stage renal disease. Similarly, Hodges teaches end stage renal disease, progressive renal insufficiency, and proteinuria as characterized by deficiencies in collagen IV protein, which can be caused by mutations in COL4A3, and/or COL4A4 genes. Further, Demir teaches FSGS is a cause of end stage renal disease and pathogenic variants in COL4A3, COL4A4, or COL4A5 genes have been frequently identified in patients with histologic diagnosis of FSGS. See Abstract. Variants in type IV collagen genes have been suggested as the most frequent variants underlying adult-onset hereditary FSGS.
The examiner also notes that Liu teaches antithrombotic agent including antiplatelet agents showed a statistically significant effect on proteinuria.
Applicant argues that some conditions associated with proteinuria are not treated with antiplatelet agents. For example, Applicant argues that clopidogrel is not used to treat UTI’s even though proteinuria is a symptom of UTI’s.
In this case, FSGS is characterized by progression to end stage renal disease and proteinuria. FSGS is a cause of end stage renal disease and pathogenic variants in COL4A3, COL4A4, or COL4A5 genes have been frequently identified in patients with histologic diagnosis of FSGS. Variants in type IV collagen genes are the most frequent variants underlying adult-onset hereditary FSGS. Thus, Hodges is teaching administering clopidogrel to a subject that has end stage renal disease, proteinuria, and other conditions (par. 25), and wherein those symptoms are also caused by the same pathogenic variants in COL4A3 and/or COL4A4 genes.
Thus, the combination of prior art teaches administration of clopidogrel to a subject with those symptoms characteristic of FSGS wherein those symptoms are caused by the same genetic variants.
The examiner acknowledges that Hodges teaches the use of clopidogrel in these subjects to “primarily prevent” or secondarily prevent acute thrombus formation induced by treatment. However, the instant claims are open-ended to combination therapy of any type and dependent claim 12 includes additional active agents that include a vast group of agents. Even if this were not the case, it is not clear that the categories of drugs claimed in claim 12 do not encompass the primary treatments taught by Hodges as Hodges is directed to administration of recombinant human collagen IV protein. See par.’s 59 and 113, e.g.
Moreover, to address the requirement in the claims that the subject must have FSGS and not just prevent it with a sole active agent, the examiner notes that Troost et al., is applied. Troost et al., “Proteinuria Reduction and Kidney Survival in Focal Segmental Glomerulosclerosis,” AJKD Vol 77, Issue 2, published online August 10, 2020.
Troost teaches that remission of proteinuria has been shown to be associated with lower rates of kidney progression among people with FSGS. See Abstract. In view of Liu, we know that antithrombotic agents including antiplatelet agents show a statistically significant effect on proteinuria. Troost also explains that most clinical trials examine proteinuria. UPCR is used interchangeably with proteinuria. Troost explains that the results are a growing body of evidence that in subjects with FSGS, they will benefit from a reduction in proteinuria. See p222-223, bridging par.
Status of the Claims
Claims 1-5, 7- 9, 11, and 12 are pending and examined.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-5, 7-9, 11, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Cravedi et al., “Recent Progress in the Pathophysiology and Treatment of FSGS Recurrence,” American Journal of Transplantation 2013; 13: 266-274, in view of Hodges et al., (US2018/0207240), in view of Demir et al., “Variations of type IV collagen-encoding genes in patients with histological diagnosis of focal segmental glomerulosclerosis,” Pediatric Nephrology (2020) 35:927-936, in view of Liu et al., Antithrombotic drug therapy for IgA nephropathy: a meta analysis of randomized controlled trials,” Internal Medicine 2011; 50(21): 2503-2510, and FDA Label for clopidogrel bisulfate 2016, and in view of Troost et al., “Proteinuria Reduction and Kidney Survival in Focal Segmental Glomerulosclerosis,” AJKD Vol 77, Issue 2, published online August 10, 2020.
Cravedi indicates that FSGS is a glomerular disease characterized by proteinuria and frequent progression to end-stage renal disease.
Hodges teaches treating conditions characterized by deficiencies in collagen IV protein, including end stage renal disease, progressive renal insufficiency, and proteinuria. See par. 25 and prior art claim 18. Such can be caused by mutations in COL4A3, and/or COL4A4 genes. See par. 26. Treatment can include administration of an agent including clopidogrel as an antiplatelet drug. See prior art claim 27. Further, claim 17 is shown below:
17. The method of claim 16, wherein said one or more deficiencies of α3(IV) chain are caused by mutations in the COL4A3 gene; said one or more deficiencies of α4(IV) chain are caused by mutations in the COL4A4 gene; and said one or more deficiencies of α5(IV) chain are caused by mutations in the COL4A5 gene.
The dosage form for administration can be a liquid, solid, semi-solid, solution tablet, pill, powder, and more. See par. 244. Injectable forms are preferred. See par. 245. The composition can be administered intravenously, subcutaneous, intrathecally, intraocularly, intracranially, e.g. See par. 254 and prior art claim 29.. This is a systemic form. Clopidogrel is the example of an ADP receptor inhibitor. See par. 265. Combination therapy is contemplated with recombinant collagen protein, NSAIDs, antibodies, and many other drugs. See prior art claims 10 and 27.
Demir teaches FSGS is a cause of end stage renal disease and pathogenic variants in COL4A3, COL4A4, or COL4A5 genes have been frequently identified in patients with histologic diagnosis of FSGS. See Abstract. Variants in type IV collagen genes have been suggested as the most frequent variants underlying adult-onset hereditary FSGS. See p927.
Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978).
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985); and Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). The FDA label for clopidogrel includes a dose of 75 mg for platelet inhibition. This would be one potential starting point for optimization of a known result-effective variable.
Liu teaches antithrombotic agent including antiplatelet agents showed a statistically significant effect on proteinuria.
Troost teaches that remission of proteinuria has been shown to be associated with lower rates of kidney progression among people with current FSGS. See Abstract. In view of Liu, we know that antithrombotic agents including antiplatelet agents show a statistically significant effect on proteinuria. Troost also explains that most clinical trials examine proteinuria. UPCR is used interchangeably with proteinuria. Troost explains that the results are a growing body of evidence that in subjects with FSGS, they will benefit from a reduction in proteinuria. See p222-223, bridging par.
It would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the instant application to combine the teachings of the prior art to arrive at the claimed methods. One would be motivated to do so because proteinuria and progression to end-stage renal disease are known to be defining symptoms of FSGS. Further, Hodges teaches treating conditions characterized by deficiencies in collagen IV protein, including end stage renal disease, progressive renal insufficiency, and proteinuria, including that caused by mutations in COL4A3, and/or COL4A4 genes. Treatment can include administration of an agent including clopidogrel as an antiplatelet drug. Even further, Demir teaches FSGS is a cause of end stage renal disease and pathogenic variants in COL4A3, COL4A4, or COL4A5 genes have been frequently identified in patients with histologic diagnosis of FSGS. See Abstract. Variants in type IV collagen genes have been suggested as the most frequent variants underlying adult-onset hereditary FSGS. As such, it would have been prima facie obvious to treat proteinuria and renal disease with the anti-platelet inhibitor clopidogrel. Further, such would be used if the cause of the symptoms is a mutation in the COL4A3 and/or COL4A4 genes, which are frequent variants identified in patients diagnosed with FSGS. The dose used is that known to be acceptable to inhibit platelet activity and the forms and route of administration are taught. Even if proteinuria is taught as a mechanism by which treatment occurs in subjects with FSGS, Troost explains that a specific goal is to reduce proteinuria in those subjects as it will benefit kidney function. As such, there is a reasonable and predictable expectation of success in administering the claimed agent to the claimed subject population as combination or monotherapy and an obvious and optimizable dosage. Li teaches monotherapy will reduce proteinuria and as such, would be expected to work as monotherapy.
As such, no claim is allowed.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628
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