DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment filed April 9, 2026, has been received and entered.
Claims 1-10 are cancelled.
Claims 11-24 are pending and examined on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11-24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “likely” in claims 11 and 18 is a relative term which renders the claim indefinite. The term “likely” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what are the metes and bounds of “likely to progress.” It is unclear what is the probability of end stage kidney disease occurring for the PLA2R-negative membranous nephropathy to be considered “likely to progress” to it. Since claims 11 and 18 are indefinite, then their dependent claims, claims 12-17 and 19-24, are rendered indefinite. Therefore, claims 11-24 are rejected under 35 U.S.C. 112(b).
Claim 18 is rendered indefinite by “a mammal identified as having kidney tissue that does not express a polypeptide.” It is unclear whether that mammal is a “mammal having a PLA2R-negative membranous nephropathy likely to progress to end stage kidney disease” as recited in line 1-2 of claim 18. Since claim 18 is indefinite, then its dependent claims, claims 19-24, are rendered indefinite. Therefore, claims 18-24 are rejected under 35 U.S.C. 112(b). For the purpose of applying prior art, the “mammal identified as having kidney tissue that does not express a polypeptide” of claim 18 is being interpreted as having a PLA2R-negative membranous nephropathy likely to progress to end stage kidney disease.
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 11-24 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.
The limitation in claims 11 and 18 of treating a mammal having a PLA2R-negative membranous nephropathy likely to progress to end stage kidney disease, is not supported by the specification as filed. Further still, the specification does not provide support for step (a) of claim 11. Example 1 of the specification demonstrates that these limitations lack support.
In particular, Example 1 includes a section regarding EXT1/EXT2-negative lupus membranous nephritis (LMN) which starts on page 17, line 1 and ends at page 18, line 19. This section indicates evaluation of an immunofluorescence study for PLA2R in 10 cases, all of which were negative (page 17, line 29 through page 18, line 1). Those 10 cases are directed to a mammal having a PLA2R-negative membranous nephropathy. However, there is no teaching that those 10 PLA2R-negative membranous nephropathy cases are “likely to progress to end stage kidney disease” as recited in claims 11 and 18. Additionally, there is no teaching that those 10 cases are identified as “likely to progress to end stage kidney disease,” wherein said identifying comprises determining that kidney tissue from the mammal does not express an EXT1 polypeptide or an EXT2 polypeptide, as recited in step (a) of claim 11.
Further still, there is no teaching that an immunosuppressant is administered to specifically the 10 cases of PLA2R-negative membranous nephropathy, as recited in claims 11 and 18. It is noted that there is a study in Example 1 in which the majority of 96 cases of EXT1/EXT2-negative LMN received immunosuppressants (page 22, line 8 through page 23, line 13; in particular, page 22, line 9 and page 23, lines 9-11). However, there is no disclosure with respect to that study that they included cases having PLA2R-negative membranous nephropathy “likely to progress to end stage kidney disease.”
As noted above, the recitation “likely to progress to end stage kidney” renders the claims indefinite. A clinical follow-up was performed on 96 of the 252 EXT1/EXT2-negative LMN cases in which only 18.8% of the cases developed early stage kidney disease (ESKD) (Table 2 on pages 19-20). In another clinical study on 65 cases of EXT1/EXT2-negative LMN cases without proliferative features (Pure Class V), only 16.9% of the cases developed ESKD (Table 3 on pages 20-21). For the follow-up of 31 cases of EXT1/EXT2-negative LMN with proliferative features (class V + class III/IV lupus nephritis), only 22.6% of the cases developed ESKD (Table 4 on page 22). Given that such low percentages (less than 50%) of the EXT1/EXT2-negative cases of membranous nephropathy developed end stage kidney disease, then it is unclear that there is support for the limitation in claim 11 of identifying PLA2R-negative membranous nephropathy as “likely to progress to end stage kidney disease,” wherein said identifying comprises determining that kidney tissue from said mammal does not express a polypeptide, wherein said polypeptide is an EXT1 polypeptide or an EXT2 polypeptide – This depends on the meaning of “likely to progress to end stage kidney disease.” Moreover, it is unclear that there is even a correlation between the kidney tissue not expressing EXT1 polypeptide or EXT2 polypeptide and end stage kidney disease given the low percentage of the EXT1/EXT2-negative cases developing end stage kidney disease. While the specification states that during the course of the disease, patients who were EXT1/EXT2-negative evolved more frequently to ESKD, this is in comparison with patients who were EXT1/EXT2-positive (page 25, lines 15-17; Table 3; page 28, lines 20-21). This is not directed to the likelihood of PLA2R-negative membranous neuropathy progressing to end stage kidney disease, nor is it directed to the identification of PLA2R-negative membranous neuropathy as likely to progress to ESKD comprising determining that the kidney tissue from the mammal (the patient) does not express EXT1 polypeptide or EXT2 polypeptide. The claims do not require comparison with a mammal having membranous nephropathy that expresses EXT1 and EXT2.
While Applicant was in possession of a portion of the claimed invention, the full scope of the claimed invention, specifically a method for treating a mammal having a PLA2R-negative membranous nephropathy likely to progress to end stage kidney disease comprising administering an immunosuppressant to said mammal, and step (a) of claim 11, is not fully described in the specification. As such, Applicant was not in possession of the full scope of the claimed invention at the time of filing. Because the specification as filed fails to provide clear support for the new claim language, a new matter rejection is clearly proper.
Notice Re: Prior Art Available Under Both Pre-AIA and AIA
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.
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.
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 of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 18-24 are rejected under 35 U.S.C. 103 as being unpatentable over Sethi (JASN. June 2019. 30: 1123-1136. Listed on IDS filed 4/4/24) in view of Lai (Journal of the Formosan Medical Association. 2015. 114: 102-111).
Sethi studied 224 cases of biopsy-proven PLA2R-negative membranous nephropathy (MN) in pilot and discovery cohorts (Methods section of abstract). In particular, kidney biopsy samples from patients (directed to a mammal that is a human, meeting limitation of instant claim 19) were studied (page 1124, left column, second and third paragraphs). Mass spectrometry was used for identifying proteins in the biopsy specimens (page 1124, paragraph bridging left and right columns). Immunohistochemical (IHC) staining for exostosin 1 (EXT1) and exostosin 2 (EXT2) was performed on kidney biopsy specimens (page 1124, right column, second paragraph). Of 224 cases of PLA2R-negative MN which underwent the IHC staining, 198 (88.4%) cases were negative for EXT1 and EXT2 (paragraph bridging pages 1126 and 1127). In determining that 198 PLA2R-negative MN cases were negative for EXT1 and EXT2, then Sethi discloses a mammal having a PLA2R-negative membranous nephropathy and identified as having kidney tissue that does not express a polypeptide, wherein said polypeptide is an EXT1 polypeptide or an EXT2 polypeptide, meeting a limitation of instant claim 18.
Sethi differs from the claimed invention in that Sethi does not disclose that, in a PLA2R-negative MN patient having a biopsy sample negative for EXT1 and EXT2 (directed to the claimed mammal having a PLA2-R negative membranous nephropathy, the mammal identified as having kidney tissue that does not express an EXT1 polypeptide or an EXT2 polypeptide), the PLA2R-negative membranous nephropathy is a PLA2R-negative membranous nephropathy likely to progress to end stage kidney disease, nor does Sethi disclose treating said patient comprising administering an immunosuppressant to said patient.
Lai discloses that 30-40% of membranous nephropathy (MN) patients progress toward end-stage renal disease within 5-15 years (page 103, left column, first paragraph). Also, immunosuppressive agents are central to the treatment of membranous nephropathy (page 103, left column, first paragraph).
Before the effective filing date of the claimed invention, for the PLA2R-negative MN cases found negative for EXT1 and EXT2 in Sethi, it would have been obvious to the person of ordinary skill in the art that at least some of the cases are ‘likely to progress’ to end stage kidney disease, wherein ‘likely to progress to end stage kidney disease’ is being interpreted by the Examiner as any non-zero probability of developing end stage kidney disease. One of ordinary skill in the art would have expected this based on the teachings in Lai that 30-40% of membranous nephropathy patients progress toward end-stage renal disease within 5-15 years. Moreover, before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to administer an immunosuppressive agent to the EXT1/EXT2-negative PLA2R-negative MN patients of Sethi. One of ordinary skill in the art would have been motivated to do this because it is a recognized and central treatment of membranous nephropathy, as indicated in Lai.
Therefore, Sethi in view of Lai renders obvious instant claims 18-22 and 24.
Regarding instant claim 23, Sethi discloses that laser capture microdissection was also performed for protein identification by mass spectrometry in their study (page 1124, paragraph bridging left and right columns). Thus, the references also render obvious instant claim 23.
Claims 18-24 are rejected under 35 U.S.C. 103 as being unpatentable over Hanset (Am. J. Kidney Dis. 2020. 76(5): 624-635. Available online July 12, 2020. Listed on IDS filed 4/4/24; Plus Supplementary Material of 17 pages), as evidenced by Alanis (US 2002/0049403).
Hanset discloses performing podocyte antigen staining on kidney biopsies of patients with membranous nephropathy (page 625, right column, first full paragraph; page 626, left column, last paragraph; Figure 1 on page 626). Immunostaining for PLA2R, THSD7A, exostosin (EXT), and NELL-1 was performed (page 625, right column, first full paragraph). 54 MN patients were detected as being double-negative for PLA2R and THSD7A (page 626, right column, first paragraph; Figure 1 on page 626). These patients are directed to a mammal (a human patient is directed to a mammal, meeting the limitation of instant claim 19) having a PLA2R-negative membranous nephropathy, meeting a limitation of instant claim 18 .
Additionally, residual kidney tissue from patients with double-negative MN (directed to PLA2R-negative membranous nephropathy) was available for exostosin 1 and 2 (EXT1/2) staining in 39 cases (page 629, right column, second full paragraph). Eight percent (3/39) showed granular EXT1/2 staining along the glomerular basement membrane (page 629, right column, third full paragraph; Figure 1 on page 626). Therefore, 92% (36 out of the 39) of the cases were negative for EXT1/2. Those cases are directed to a mammal identified as having kidney tissue that does not express a polypeptide, wherein said polypeptide is an exostosin 1 (EXT1) polypeptide or an exostosin 2 (EXT2) polypeptide, meeting a limitation of instant claim 18.
Hanset further teaches that 41% of the double-negative MN patients were treated with immunosuppressive drugs (page 627, right column). Additionally, after a median follow-up of 4 years, kidney failure occurred in 25% of patients in the double-negative MN group (page 628, second paragraph; Table 1 on page 628). Based on these teachings, it would have been obvious to the person of ordinary skill in the art that at least some (even as few as a single patient) of the double-negative MN patients that are negative for EXT1/2 are treated with immunosuppressive drugs and also developed kidney failure in the 4-year follow-up. This would have been obvious given the percentage of double-negative MN patients treated with immunosuppressive drugs and the percentage of double-negative MN patients who developed kidney failure.
As discussed above, the double-negative MN patients that are negative for EXT1/2 are directed to a mammal having a PLA2R-negative membranous nephropathy and identified as having kidney tissue that does not express a polypeptide, wherein said polypeptide is an EXT1 polypeptide or an EXT2 polypeptide. As evidenced by Alanis, end-stage renal disease is commonly referred to as kidney failure (paragraph [0003]). Therefore, a double-negative, EXT1/2-negative MN patient that has developed kidney failure (as rendered obvious in the preceding paragraph) is directed to a mammal having a PLA2R-negative membranous nephropathy ‘likely to progress’ to progress to end stage kidney disease, wherein ‘likely to progress to end stage kidney disease’ is being interpreted by the Examiner as any non-zero probability of developing end stage kidney disease – in this case, the probability is 100% since the end stage kidney disease has occurred in that patient. Therefore, Hanset renders obvious instant claims 18-21 and 24.
Regarding instant claim 22, Hanset discloses that immunostaining for EXT was performed according to the protocols detailed in Item S1 and Figure S1 (page 625, right column, first full paragraph). Item S1 indicates that immunofluorescence staining for EXT1/2 was performed by performing antigen retrieval on FFPE sections, incubating with antibodies for EXT1 and EXT2, and evaluating stained sections using an inverse microscope (paragraph bridging pages 6 and 7 of Supplementary Material). This is directed to using immunohistochemistry to determine that the kidney tissue (Hanset’s kidney biopsy) does not express an EXT1 polypeptide and an EXT2 polypeptide. Therefore, instant claim 22 is rendered obvious.
Regarding instant claim 23, Hanset refers to studies in which laser microdissection and mass spectrometry were used to observe glomerular accumulation of EXT1/2 in subsets of patients with double-negative MN (page 629, right column, first full paragraph). For performing the method rendered obvious by Hanset, it would have been obvious use laser microdissection and mass spectrometry to detect the absence of EXT1/2 in the kidney biopsies of the double-negative MN patients, since they were found suitable for detecting glomerular accumulation of EXT1/2 in double-negative MN patients. Therefore, instant claim 23 is rendered obvious.
Response to Arguments
Applicant’s arguments, filed April 9, 2026, with respect to the rejection under 35 U.S.C. 103 of claims 11-24 as being unpatentable over Sethi in view of Beck and Aaltonen have been fully considered and are persuasive. In particular, the rejection has been overcome by the amendments to claims 1 and 18 since the rejection did not address the embodiment of Sethi in which the mammal has a PLA2R-negative membranous nephropathy, nor amended step (a) of claim 11. Therefore, the rejection has been withdrawn.
However, upon further consideration, a new ground(s) of rejection is made in view of the newly cited references Lai, Hanset, and Alanis, with Lai as a secondary reference to the previously cited Sethi reference. Additionally, new rejections under 35 U.S.C. 112(b) and 35 U.S.C. 112(a) are made.
Conclusion
No claims are allowed.
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/SUSAN E. FERNANDEZ/ Examiner, Art Unit 1651
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