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 .
Claims 1-20 are cancelled.
Claims 21-35 are pending and under examination on the merits.
Priority
This application is a 371 of PCT/US2023/063654, filed 03/03/2023, which claims benefit of US Provisional Application No. 63/318,171, filed 03/09/2022.
IDS
The information disclosure statements (IDS’) filed 06/09/2025 and 04/08/2026 has been considered.
Drawings
The drawings are objected to because figures 2A-C are illegible (see for example, MPEP §608.02(b)). Correction is required. The objection to the drawings will not be held in abeyance.
Claim Interpretation
Where independent claims 21 and 34 are directed towards methods “comprising (i) autoantibodies specific for …or (ii) kidney tissue comprising…, this recitation is being interpreted consistent with a method claim to be an active step of identifying/detecting autoantibodies specific for a FAT1 polypeptide or kidney tissue comprising an elevated level of said FAT1 polypeptide, thereby identifying the subject as having membranous nephropathy being in need of treatment therefore.
Consistent with page 11 bridging page 12 of the specification, an “elevated level” is any level above the median level of FAT1 polypeptides present within normal kidney tissue (e.g., a normal GBM) of comparable mammals not having membranous nephropathy. Therefore, the control may be normal kidney tissue or kidney tissue not having MN.
Claim Objections
Applicant is advised that should claim 21 be found allowable, claims 34 and 35 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 21-24, 31, and 33-35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The genus of immunosuppressants comprises a wide variety of biologically distinct classes (calcineurin inhibitors, JAK inhibitors, antibodies, etc.). There is insufficient description for the breadth of the genus claim for treating membranous nephropathy. Regarding the subgenus of DNA-damage inducers, the instant specification of discloses that chlorambucil is effective for treating MN identified by autoantibodies to FAT1 or an elevated FAT1 level in kidney tissue (see for example, lines 18-20 at page 7 of the specification). Looking to the prior art, the only DNA damage inducers shown to treat membranous nephropathy (MN) are cyclophosphamide and chlorambucil (see for example, paragraph 0106 of Salant et al (US 20130280738 A1; US Patent citation 6 as cited on the 06/09/2025 IDS)). Regarding the subgenus of antibodies, the instant Application only specifically discloses rituximab (see for example, page 3 lines 25-30 of the instant specification).
The state of the prior art teaches that the state of the art regarding nephropathy treatment is uncertain. Foster (Antibody therapy points to a new treatment era for primary membranous nephropathy, DDN, obtained from: https://www.drugdiscoverynews.com/antibody-therapy-points-to-a-new-treatment-era-for-primary-membranous-nephropathy-17262 (pub. 2026)) teach that the natural course of pMN is highly variable (see for example, page 2 at paragraph 3). Foster teaches that there are currently no approved therapies for primary membranous nephropathy (pMN) (see for example, page 2 at paragraph 4). This teaching is understood to support that there is no approved treatment specifically validated for safely and effectively treating primary nephropathy. Foster further teaches that historically, pMN has been treated with a combination of supportive care and broad immunosuppression, with treatment intensity guided by a patient’s risk of progression. Foster explains that calcineurin inhibitors such as tacrolimus are commonly used in moderate-risk patients, while higher-risk individuals may receive more potent regimens, including alkylating agents like cyclophosphamide. Although these approaches can reduce proteinuria, cumulative toxicity remains a concern and relapse is common with tacrolimus. Foster goes on to teach that this treatment gap has driven Roche and its Genentech unit to advance Gazyva (obinutuzumab), a type 2 anti-CD20 monoclonal antibody already approved in oncology and lupus nephritis, into late-stage development for pMN. However, even with data pointing to a role for B cell depleting therapy for treating pMN, 20 to 40 percent of patients fail to respond to an initial course of rituximab, and between five and 28 percent of patients relapse after achieving remission (see for example, pages 2-3).
Peritore et al (Medicina 2023, 59, 1997. https://doi.org/10.3390/medicina59111997) further teach that up to 30% of patients do not respond to therapy (such as immunosuppressive therapy with various drugs such as cyclophosphamide, steroids, calcineurin inhibitors or rituximab) despite supportive care and appropriate immunosuppressive therapy, further supporting that treatment of MN is unpredictable. Peritore et al additionally teach that new therapeutic approaches with drugs such as adrenocorticotropic hormone, belimumab, anti-plasma cell antibodies or complement-guided drugs are currently being tested. However, special attention needs to be paid to the choice of therapy in secondary forms or in specific clinical contexts such as membranous disease in children, pregnant women and patients undergoing kidney transplantation (see for example, the abstract at page 1).
Therefore, only chlorambucil and cyclophosphamide from the subgenus of DNA-Damage inducers, the genus of mTOR inhibitors, the genus of calcineurin inhibitors, the genus of steroids/corticosteroids, and rituximab from the subgenus of antibodies/B-cell depleting therapies are deemed to have been adequately described by the instant disclosure when viewed in the context of the state of the art prior to the effective filing date within the recited genus of immunosuppressants.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised that the cited reference names an additional author for whom it is unclear whether the disclosure was obtained from an inventor or is the author contributed individually to the disclosed matter. Applicant is advised to refer to MPEP §2153.01(a).
Claims 21-22, 24-28, and 31-35 is/are rejected under 35 U.S.C. 103 as being obvious over Sethi et al (J Am Soc Nephrol 32: 2021; NPL citation 4 as cited on the 04/08/2026 IDS) in view of Salant et al (US 20130280738 A1; US Patent citation 6 as cited on the 06/09/2025 IDS).
The applied reference has a common author/inventor and affiliate institution/assignee with the instant application. Based upon the earlier public availability date of the reference with an author named who is not listed as an inventor, it constitutes prior art under 35 U.S.C. 102(a)(1).
Regarding claim 21, Sethi et al performed laser microdissection and mass spectrometry (MS/MS) of glomeruli of 230 cases of PLA2R-negative MN to detect novel proteins/antigens in membranous nephropathy (MN). These included PLA2R-negative MN developing in the setting of hematopoietic stem cell transplant (HSCT) and de-novo MN in the kidney transplant. Sethi et al detected a protocadherin FAT1 (FAT1) in 9 out of 9 cases of PLA2R-negative MN. FAT1was not detected by MS/MS in 115 control cases that included time 0 transplant, minimal change disease, FSGS, diabetes and IgA nephropathy. FAT1 was also not detected in 28 cases of PLA2R-positive MN. No case of FAT1-associated MN was detected in a nontransplant setting. Sethi et al conclude that FAT1 appears to be a unique protein found in MN developing in the setting of HSCT and de-novo MN following kidney transplant. Sethi et al finally teach that further studies to localize FAT1 on the glomerular basement membranes and detect circulating antibodies are ongoing (see the abstract PO1467 at column 1 of page 463). While no species is provided in terms of the test subjects, the median age (56+/- 9 years is consistent with a human subject) with there being nothing in the disclosure to suggest that the association of FAT1 and MN would not be expected to be present in mammals, including humans.
Sethi et al do not teach treatment of MN comprising administration of an immunosuppressant to a mammal.
However, Salant et al teach a method of prognosis evaluation in a subject being treated for membranous nephropathy comprising determining efficacy of treatment by detecting a decrease in the level of PLA2R antibodies at a second timepoint relative to a first time point, where the treatment for MN is an immunosuppressive treatment (see for example, paragraph 0009), where the immunosuppressive treatment for MN may be, for example, cyclosporin, tacrolimus, azathioprine, infliximab, omalizumab, daclizumab, adalimumab, eculizumab, efalizumab, natalizumab, omalizumab, rapamycin, cyclophosphamide, chlorambucil, or rituximab (see for example, paragraph 0106). The subject is intended to be human, but may be a different mammal (see for example, paragraphs 0006 and 0021).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the claimed invention. The artisan would have been motivated to make and use the invention as claimed to identify mammals, including humans, as having MN and treating said MN. Where Salant et al teach that idiopathic MN is treated with an immunosuppressant, the artisan would have found it obvious to treat identified MN which is idiopathic (also called primary or de novo MN) or related to a transplant (also called secondary or recurrent) with such an immunosuppressant. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references prior to the effective filing date.
Regarding claim 22, as set forth above, the reference make obvious the method of claim 21 wherein the subject is a human.
Regarding claim 24, the combined reference, while not teaching the measured incidence of FAT1 in kidney tissue having MN developing in the setting of HSCT and de-novo MN following kidney transplant relative to normal kidney tissue, does teach that FAT1 was not detected by MS/MS in 115 control cases that included time 0 transplant, minimal change disease, FSGS, diabetes and IgA nephropathy. FAT1 was also not detected in 28 cases of PLA2R-positive MN. No case of FAT1-associated MN was detected in a nontransplant setting. Therefore, the teachings of Sethi suggest that the presence of FAT1 is highly specific to PLA2R-negative MN such that the level of FAT1 detected would be elevated relative to a level detected in normal kidney tissue or kidney tissue not having MN (such as the IgA nephropathy tissue taught by Sethi et al).
Regarding claims 25-26, as set forth above, the reference make obvious the method of claim 21 wherein the immunosuppressant may be a B-cell inhibitor such as rituximab.
Regarding claims 27-28, as set forth above, the combined references make obvious the method of claim 21 wherein the immunosuppressant may be a calcineurin inhibitor such as cyclosporin or tacrolimus.
Regarding claims 31-32, as set forth above, the combined references make obvious the method of claim 21 wherein the immunosuppressant may be a DNA damage inducer such as chlorambucil.
Regarding claim 33, the claim does not recite a further active step of new/different reagent for using the method of instant claim 21. Claim 33 instead recited a result passively obtained from practicing the method of claim 21. Therefore, where the combined references make obvious claim 21, the method resulting from the combined prior art is presumed to obtain the recited result because the same active steps and reagents are used within the same population, therefore, the result is understood to be the same absent an evidenced showing to the contrary.
Regarding claims 34-35, the combination of the prior art references set forth above makes obvious a method for treating membranous nephropathy in a mammal comprising administering an immunosuppressant to the mammal, said mammal being identified as having MN where an elevated level of FAT1 in kidney tissue is detected.
Claims 29-30 is/are rejected under 35 U.S.C. 103 as being obvious over Sethi et al in view of Salant et al, as applied to claims 21-22, 24-28, and 31-35 above, as evidenced by Sehgal (Ther Drug Monit. 1995 Dec;17(6):660-5. doi: 10.1097/00007691-199512000-00019).
Regarding claims 29-30, as set forth above, Sethi et al in view of Salant make obvious the method of claim 21 wherein the administered immunosuppressant is rapamycin which is synonymous with sirolimus as evidenced by Sehgal (see for example, the first sentence of the abstract).
Therefore, claims 29-30 are deemed to be made obvious for the same reason that claim 21 is made obvious by Sethi et al in view of Salant et al in view of the evidentiary teachings of Sehgal.
Claim(s) 21-22, 24-28, and 31-35 is/are rejected under 35 U.S.C. 103 as being unpatentable over Braun et al (Journal of Biological Chemistry, 2007; 282, 22823-22833) in view of Salant et al (US 20130280738 A1; US Patent citation 6 as cited on the 06/09/2025 IDS) as evidenced by Cleveland Clinic (Membranous Nephropathy available as of 07/19/2021 as evidenced by Wayback Machine, obtained from: https://web.archive.org/web/20210719153838/https://my.clevelandclinic.org/health/diseases/21154-membranous-nephropathy).
Regarding claim 21, Braun et al teach that cadherin FAT1 is localized along the leading edge of mammalian cells and is necessary for polarization and directed migration. It is essential for maintenance of the complex cytoarchitecture of the glomerular filtration barrier within the kidney. Braun et al identified three novel splice isoforms of FAT1 with important functional differences in comparison with wild-type FAT1, FAT1(WT). A shift of FAT1(WT) expression toward a predominance of FAT1(+12) was observed in vivo when glomeruli from healthy individuals were compared with those from patients affected by membranous glomerulonephritis (synonymous with membranous nephropathy as evidenced by Cleveland Clinic at the ‘What is membranous nephropathy’ section) (see for example, the abstract at column 1 of page 22823 and figure 4g and its caption at column 1 of page 22828). Braun et al teach that human biopsies from glomeruli were used (see for example, the REAL Time RT-PCR from Human Biopsies section at page 22824).
Braun et al et al do not teach treatment of MN comprising administration of an immunosuppressant to a mammal.
However, Salant et al teach a method of prognosis evaluation in a subject being treated for membranous nephropathy comprising determining efficacy of treatment by detecting a decrease in the level of PLA2R antibodies at a second timepoint relative to a first time point, where the treatment for MN is an immunosuppressive treatment (see for example, paragraph 0009), where the immunosuppressive treatment for MN may be, for example, cyclosporin, tacrolimus, azathioprine, infliximab, omalizumab, daclizumab, adalimumab, eculizumab, efalizumab, natalizumab, omalizumab, rapamycin, cyclophosphamide, chlorambucil, or rituximab (see for example, paragraph 0106). The subject is intended to be human, but may be a different mammal (see for example, paragraphs 0006 and 0021).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the claimed invention. The artisan would have been motivated to make and use the invention as claimed to identify mammals, including humans, as having MN and treating said MN. Where Salant et al teach that idiopathic MN is treated with an immunosuppressant, the artisan would have found it obvious to treat identified MN which is idiopathic (also called primary or de novo MN) or related to a transplant (also called secondary or recurrent) with such an immunosuppressant. Measurement of the FAT1(+12) variant is deemed to be within the broadest reasonable interpretation of measuring/detecting an elevated level of FAT1 in MN kidney tissue relative to non-MN kidney tissue or normal kidney tissue, such that Braun et al teaching that FAT1(+12) is elevation in MN relative to normal kidney tissue (see for example, figure 4g and its caption at page 22828) falls within the scope of the instant claim as presently drafted where no preclusive definition is clearly provided for in the instant specification. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references prior to the effective filing date.
Regarding claim 22, as set forth above, the reference make obvious the method of claim 21 wherein the subject is a human.
Regarding claim 24, as set forth above, Braun et al teach that the FAT1(+12) variant is elevated in MN kidney tissue relative to normal/control kidney tissue so as to fall within the instant claim scope, making obvious the claim as presently drafted.
Regarding claims 25-26, as set forth above, the reference make obvious the method of claim 21 wherein the immunosuppressant may be a B-cell inhibitor such as rituximab.
Regarding claims 27-28, as set forth above, the combined references make obvious the method of claim 21 wherein the immunosuppressant may be a calcineurin inhibitor such as cyclosporin or tacrolimus.
Regarding claims 31-32, as set forth above, the combined references make obvious the method of claim 21 wherein the immunosuppressant may be a DNA damage inducer such as chlorambucil.
Regarding claim 33, the claim does not recite a further active step of new/different reagent for using the method of instant claim 21. Claim 33 instead recited a result passively obtained from practicing the method of claim 21. Therefore, where the combined references make obvious claim 21, the method resulting from the combined prior art is presumed to obtain the recited result because the same active steps and reagents are used within the same population, therefore, the result is understood to be the same absent an evidenced showing to the contrary.
Regarding claims 34-35, the combination of the prior art references set forth above makes obvious a method for treating membranous nephropathy in a mammal comprising administering an immunosuppressant to the mammal, said mammal being identified as having MN where an elevated level of FAT1 (FAT1(+12)) in kidney tissue is detected.
Claims 29-30 is/are rejected under 35 U.S.C. 103 as being obvious over Braun et al in view of Salant et al as evidenced by Cleveland Clinic, as applied to claims 21-22, 24-28, and 31-35 above, as evidenced by Sehgal (Ther Drug Monit. 1995 Dec;17(6):660-5. doi: 10.1097/00007691-199512000-00019).
Regarding claims 29-30, as set forth above, Braun et al in view of Salant et al as evidenced by Cleveland Clinic make obvious the method of claim 21 wherein the administered immunosuppressant is rapamycin which is synonymous with sirolimus as evidenced by Sehgal (see for example, the first sentence of the abstract).
Therefore, claims 29-30 are deemed to be made obvious for the same reason that claim 21 is made obvious by the combination of Braun et al and Salant et al as evidenced by Cleveland Clinic in view of the evidentiary teachings of Sehgal.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Chung et al (Front. Immunol. 13:1036249. doi: 10.3389/fimmu.2022.1036249) cite to Sethi et al (NPL citation 4 as cited on the 04/08/2026 IDS) to support that FAT1 is related to membranous nephropathy. Chung et al is not available to serve as prior art.
Passerini et al (Front. Immunol. 10:1326. doi: 10.3389/fimmu.2019.01326 (2019)) teach that primary and recurrent MN may be treated with an immunosuppressant.
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
Prosecution Insights