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 .
Application Status
The amended claims filed on October 8, 2025 with the Response to the non-final Office Action are acknowledged. Claims 1-20 are canceled. Claims 21-34 are newly added.
Claims 21-34 are pending and under examination herein.
Objection to the Specification Withdrawn
The objection to the specification is withdrawn in view of Applicant's amendment thereto.
Claim Rejections Withdrawn
All prior rejections of claims 1-20 are rendered moot by the cancelation of the claims.
NEW OBJECTIONS AND REJECTIONS NECESSITATED BY CLAIM AMENDMENT
Claim Objections
Claims 21-29 are objected to because claim 21, at line 3, appears to contain a typographical error (“anti-antibody”). Dependent claims 27-29 later refer to “the antibody, or antigen-binding fragment thereof” which supports that “anti-antibody” is merely a typographical errot. The text of claim 21 should be corrected to recite “an antibody” such that the limitations set forth in the dependent claims have antecedent basis for the instantly claimed invention.
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.
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.
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.
Claims 21-34 are rejected under 35 U.S.C. 103 as being unpatentable over Wei (Nature Medicine (2011) 17: 952-960; cited in PTO-892 mailed July 16, 2025) in view of Craik (US 9,029,509 B2; published May 12, 2015; cited in PTO-892 mailed July 16, 2025). This is a new rejection necessitated by claim amendment.
Wei teaches that FSGS is a cause of proteinuric kidney disease and that recurrence of FSGS occurs in about 30% of FSGS patients after kidney transplant (Introduction). Wei investigated whether suPAR might be a candidate “circulating factor” that contributes to recurrent FSGS based on recent observations that uPAR plays a role in glomerular disease (Introduction). Wei investigated in mouse models whether suPAR causes or is caused by FSGS, and observed that suPAR induced FSGS phenotypes (Results, pages 956-958; Figures 4-5). Relevant to claims 21, 23-24, 30, and 32-33, blocking the action of suPAR by administering an anti-uPAR monoclonal antibody to mice expressing sPlaurWT protected mice from proteinuria, improved kidney morphology and histopathology scores, and improved podocyte foot process structures (Results, page 958; Figure 6), effectively treating the FSGS phenotype and inhibiting the activity of uPAR and/or suPAR. The sPlaurWT mice have detectable levels of suPAR in blood (Results, page 957). Subjects with FSGS would be expected to be candidates for kidney transplant, further relevant to claim 25.
Pertinent to claims26-30 and 34, Wei shows in human subjects that serum concentrations of suPAR were significantly higher in FSGS patients when compared to those of healthy subjects and subjects with other glomerular diseases with podocyte involvement (Results, page 951; Figure 1a). When FSGS patients were stratified into those with primary FSGS, recurrent FSGS in the allograft, and FSGS without recurrence after transplantation, the highest suPAR concentrations were observed in pre-transplantation blood from FSGS subjects who later developed recurrent FSGS after transplantation, suggesting that pre-transplantation suPAR serum concentrations may predict risk of recurrent FSGS after transplantation (Results, page 951; Figure 1b). Wei further observed that transplanted patients who had recurrent FSGS one year after transplantation displayed significantly higher levels of serum suPAR than those who did not have recurring FSGS (Results, page 951; Figure 1c; Supplementary Figure 1). Wei concludes that suPAR is a circulating, causative factor of FSGS which is elevated in the serum of approximately two-thirds of primary FSGS patients and can cause FSGS before and after transplantation (Discussion, pages 958-959). Wei discloses that blockade of suPAR using a blocking antibody specific to suPAR can modulate excessive podocyte β3 integrin activation and protect from suPAR-mediated podocyte injury (Discussion, pages 958-959).
However, Wei does not expressly teach administering an anti-uPAR antibody comprising VH CDRs comprising the amino acid sequences of SEQ ID NO: 3-5, respectively, and VL CDRs comprising the amino acid sequences of SEQ ID NO: 6-8, respectively, and comprising a heavy chain polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 1 and a light chain polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2.
Craik discloses antibodies that bind to and/or modulate the activity of uPAR, compositions comprising the same, and methods of use thereof (Abstract). Among these include an isolated antibody 2G10 which comprises VH CDRs comprising SEQ ID NO: 40, 42, and 44, respectively, and VL CDRs comprising SEQ ID NO: 34, 36, and 38, respectively, which share 100% identity with instant SEQ ID NO: 3-5, respectively, and SEQ ID NO: 6-8, respectively (e.g., Figure 1B; Table 1, col 21-23; claims 1-2 and 14-15). Craik further recites that the isolated antibody comprises a heavy chain comprising an amino acid sequence having at least 85% sequence identity to the full length VH or 2G10 (SEQ ID NO: 16) and a light chain comprising an amino acid sequence having at least 85% sequence identity to the full length VL of 2G10 (SEQ ID NO: 17), which share 100% sequence identity to instant SEQ ID NO: 1 and 2, respectively. Craik additionally claims an antibody or antigen-binding fragment thereof that competes for binding to uPAR with an antibody from clone 2G10 (e.g., claim 4). Craik shows that binding of uPA is greatly reduced in the presence of antibody 2G10 (e.g., Figure 2). Craik provides that the subjects treated in the methods of the invention may be human (e.g., col 9).
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to administer to a human subject in need thereof an anti-uPAR antibody such as that taught by Craik in the method of treating or preventing FSGS or of inhibiting uPAR and/or suPAR activity taught by Wei, comprising administering to a subject an effective amount of a neutralizing anti-uPAR antibody. The skilled artisan would have been motivated to do so because Wei discloses that serum uPAR and suPAR levels are higher in FSGS patients and that administering a neutralizing anti-uPAR antibody ameliorates FSGS symptoms in a mouse model. It would have been further obvious to carry out such a method in a subject who has undergone a kidney transplant and is at risk of recurrent FSGS (relevant to claims 26, 30, and 34), since Wei teaches that the subset of FSGS patients who developed recurrent FSGS after kidney transplant were those who displayed higher levels of serum suPAR before kidney transplant and one year after the transplant. In addition, it would have been obvious to try administering a neutralizing anti-uPAR antibody either prior to, at the time of, or following the kidney transplant (relevant to claims 27-29), to arrive at an optimal treatment regimen through the process of routine optimization. This is because Wei teaches that FSGS patients generally have higher levels of suPAR relative to both healthy controls and other patients with glomerular kidney disease, and furthermore, that those patients who had the highest risk of recurrent FSGS were those with increased serum suPAR before transplant and one year afterward. Presumably, said patients would also have had heightened levels of suPAR at the time of the transplant. Thus, Wei demonstrates that suPAR levels are heightened at multiple timepoints in FSGS patients, and that neutralization of suPAR levels is a result-effective variable that ameliorates FSGS symptoms based on data in mouse models. Furthermore, there are a finite number of timeframes at which a potential treatment may be administered to a patient relative to kidney transplant, and one of ordinary skill in the art has good reason to pursue known options within his or her technical grasp.
There would have been a reasonable expectation of success for substituting the anti-uPAR antibody 2G10 taught by Craik in the method taught by Wei because the antibody is a functional equivalent of the neutralizing antibody described by Wei and it reduces binding of uPAR to its ligand uPA, as demonstrated by Craik.
Claims 21-26 and 30-34 are rejected under 35 U.S.C. 103 as being unpatentable over Reiser (WO 2010/054189 A1; cited in PTO-892 mailed July 16, 2025) in view of Craik (US 9,029,509 B2; supra).
Reiser discloses compositions that specifically block the function or activity of uPAR or suPAR in the kidneys, and methods of treatment for renal disorders that comprise administering said compositions (e.g., Abstract; ¶ 0002). Reiser teaches that uPAR signaling in podocytes has been shown to cause glomerular disease, and that removal or blockade of this protein is a promising avenue for native organ maintenance and transplant survival (e.g., ¶ 0044). Reiser additionally teaches that patients who developed recurrent FSGS had higher suPAR serum levels pre-transplant than non-recurrent patients and healthy controls (e.g., ¶ 0008; Example 1 (pages 39-43); Figure 2). In embodiments of the invention, Reiser teaches antibodies that inhibit binding of uPAR to its ligand and administering such antibodies to a subject in need thereof in a method of treating a disease or disorder associated with pathological urokinase receptor molecules expression and/or activity, e.g., focal segmental glomerulosclerosis (FSGS) (e.g., ¶ 0049-0068; claims 1-9), relevant to claims 21, 24, 30, and 33. Reiser provides that a “patient” or “subject” refers to mammals including humans (¶ 0032). Reiser further teaches that “a patient in need thereof” may refer to a subject who is affected by or who is at risk of having a disorder characterized by proteinuria (e.g., ¶ 0033), e.g., an individual at risk of recurrent FSGS as evidenced by pre-transplant serum suPAR levels, relevant to claims 26, 30, and 34. Reiser also recites that treatment of a disease or condition can include improvement of a disease or condition by any amount, including prevention, amelioration, and elimination of the disease or condition (e.g., ¶ 00116), further relevant to claims 23 and 32.
Subjects with FSGS would be expected to be candidates for kidney transplant, further relevant to claim 25.
However, Reiser does not expressly teach administering an anti-uPAR antibody comprising VH CDRs comprising the amino acid sequences of SEQ ID NO: 3-5, respectively, and VL CDRs comprising the amino acid sequences of SEQ ID NO: 6-8, respectively, and comprising a heavy chain polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 1 and a light chain polypeptide comprising an amino acid sequence having at least 85% sequence identity to SEQ ID NO: 2, relevant to claims 22 and 31.
The teachings of Craik are recited in the 35 U.S.C. § 103 rejection above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to administer an anti-uPAR antibody such as that taught by Craik in the method of treating FSGS or of inhibiting uPAR and/or suPAR activity taught by Reiser, comprising administering to a subject an effective amount of the anti-uPAR antibody. The skilled artisan would have been motivated to do so because, as taught by Reiser, uPAR signaling in podocytes is causative of glomerular disease, and inhibition of uPAR has promise in treating proteinuria-associated renal diseases such as FSGS. Furthermore, patients at risk of developing recurrent FSGS have higher serum suPAR levels pre-kidney transplant than non-recurrent FSGS patients and healthy individuals. There would have been a reasonable expectation of success because the anti-uPAR antibody 2G10 taught by Craik is a functional equivalent of the inhibitory antibody described by Reiser and reduces binding of uPAR to its ligand uPA, as demonstrated by Craik.
Claims 21 and 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Reiser (WO 2010/054189 A1; supra) in view of Craik (US 9,029,509 B2; supra) as applied to claims 21-26 and 30-34 above, further in view of Wei (Nature Medicine (2011) 17: 952-960; supra).
The teachings of Reiser are recited in the 35 U.S.C. § 103 rejection above. However, Reiser does not expressly teach that the antibody administered in the disclosed method of treatment is administered prior to, at the time of, or following kidney transplant.
The teachings of Craik and Wei are recited in the 35 U.S.C. § 103 rejections above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to try administering an anti-uPAR antibody such as that taught by Craik in the method of treating FSGS or of inhibiting uPAR and/or suPAR activity taught by Reiser, comprising administering to a subject an effective amount of the anti-uPAR antibody, either prior to, at the time of, or following kidney transplant, to arrive at an optimal treatment regimen through the process of routine optimization. This is because Reiser and Wei teach that FSGS patients who are most at risk of recurrent FSGS after transplant have higher levels of serum suPAR pre-transplant compared to nonrecurrent patients, and Wei further teaches that recurrent FSGS patients also have elevated serum suPAR levels one year after transplant. Presumably, said patients would also have had heightened levels of suPAR at the time of the transplant. Because Wei demonstrates that suPAR levels are heightened at multiple timepoints in FSGS patients, and that neutralization of suPAR levels is a result-effective variable that ameliorates FSGS symptoms based on data in mouse models, it would have been obvious to try treating said patients at multiple time points to determine the most effective treatment regimen. Furthermore, there are a finite number of timeframes at which a potential treatment may be administered to a patient relative to kidney transplant, and one of ordinary skill in the art has good reason to pursue known options within his or her technical grasp. There would have been a reasonable expectation of success because the anti-uPAR antibody 2G10 taught by Craik is a functional equivalent of the inhibitory antibody described by Reiser and reduces binding of uPAR to its ligand uPA, as demonstrated by Craik.
Response to Arguments (Combined)
Applicant's arguments filed October 8, 2025, with respect to the rejections of record under 35 U.S.C. § 103, have been fully considered but they are not persuasive.
Applicant respectfully traverses the rejections on the grounds that at the time of the priority date of the instant application, “it was not known whether an antibody that binds to uPAR and suPAR can treat or prevent FSGS in a human subject and it was not known whether an antibody that binds to uPAR and suPAR can inhibit uPAR and suPAR activity and prevent or ameliorate FSGS in a human subject”. Remarks at pages 7-8. Applicant points to the teachings of Harel (Transplantation (2020) 104(1): 54-60), published after Wei and Reiser, who states that the role of suPAR in FSGS as the circulating factor or as a predictor of recurrence after transplantation remains controversial. Applicant submits that because the role of suPAR in FSGS was not clear, a person of ordinary skill in the art would not have had a reasonable expectation of success that blocking suPAR activity can prevent or treat FSGS. Remarks at pages 8-9.
In response, it is first noted that Applicant’s cited reference of Harel (which is co-authored by the inventors of the instant application) does not seek to answer or test whether an antibody that binds to uPAR/suPAR can (1) treat or prevent FSGS or (2) inhibit uPAR/suPAR activity and prevent or ameliorate FSGS as presented in the instant claims. A stated goal of Harel was to determine whether the findings of Wei (with respect to the effect of suPAR on podocyte injury, effacement of foot processes, and proteinuria) could be replicated, as two other “well-designed” mouse studies by Cathelin and Spinale failed to show that infusions of suPAR result in proteinuria and effacement of podocytes (e.g., Introduction). Harel acknowledges that the study design of these studies differed, as Wei used uPAR recombinant (uPAR-/-) mice while the other two studies used wild-type (WT) mice, and that these differences might explain the seemingly disparate findings (e.g., Abstract; Introduction). Harel later acknowledges several other factors that could explain discordance between the early findings of Wei and later clinical findings, “including the degree of renal failure of the patients because the glomerular filtration rate is an important determinant of suPAR levels, ethnicity, the heterogenicity of the disease itself, and methodology for measuring suPAR levels” (Discussion). When Harel compared the effect of injecting recombinant soluble uPAR-Fc chimera (smuPAR-Fc) on proteinuria in WT and uPAR-/- mice, Harel made seemingly disparate conclusions about the results, stating both that “Recombinant smuPAR … did not cause proteinuria in uPAR-deficient mice” (header in left column, Results at page 57) and “Injection of 100 μg smuPAR-Fc chimera to uPAR-/- mice leads to proteinuria; however, injection of Fc by itself was sufficient to induce proteinuria in those mice (Figure 1C)” (Results, page 57, left column). Neither the Results section nor Figure 1C of Harel provide a clear showing of whether the differences in proteinuria among the experimental groups rise to the level of statistical significance.
In the absence of a clear indication of whether WT or uPAR-deficient mice are a more physiologically relevant experimental model for FSGS, it would make sense for one of ordinary skill in the art to lean on observations gleaned directly from human patients with FSGS. To this end, the cited references of Wei (for which Reiser is a co-author) and Reiser each describe a clear relationship in human patients between the serum concentration of suPAR and recurrence/non-recurrence of FSGS, which would motivate one of ordinary skill in the art to further explore possible treatment methods that act on this elevated biomarker. The teachings of Wei and Reiser both suggest that blockade of uPAR/suPAR would achieve downstream effects that serve to treat or prevent recurrence of FSGS. Directly pertinent to the instantly claimed methods, the combination of cited references in the rejections above clearly teach the active step of administering an antagonistic anti-uPAR/suPAR antibody to a subject (e.g., a human subject) for the purpose of inhibiting uPAR/suPAR and/or treating and preventing FSGS.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 21-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 14-15 of U.S. Patent No. 9,029,509 (cited in PTO-892 mailed July 16, 2025) in view of Wei (Nature Medicine (2011) 17: 952-960; supra).
The ‘509 patent claims an isolated antibody or antigen-binding fragment thereof that specifically binds uPAR, wherein said antibody competes for binding to uPAR with an antibody or antigen-binding fragment thereof that comprises VH CDRs comprising SEQ ID NO: 40, 42, and 44, respectively (which share 100% sequence identity to instant SEQ ID NO: 3-5, respectively), and VL CDRs comprising SEQ ID NO: 34, 36, and 38, respectively (which share 100% sequence identity to instant SEQ ID NO: 6-8, respectively), which competes for binding with an antibody from clone 2G10 (patented claims 1-2 and 4), relevant to claims 21 and 30. Patent claim 3 recites the isolated antibody or antigen-binding fragment thereof of claim 2, comprising a heavy chain comprising an amino acid sequence having at least 85% sequence identity to the full length VH of 2G10 (SEQ ID NO: 16, which shares 100% sequence identity to instant SEQ ID NO: 1) and a light chain comprising an amino acid sequence having at least 85% sequence identity to the full length VL of 2G10 (SEQ ID NO: 17, which shares 100% sequence identity to instant SEQ ID NO: 2), relevant to claims 22 and 31. In addition, the patented claims also recite an isolated antibody or antigen-binding fragment thereof comprising the full length VH of 2G10 (SEQ ID NO: 16) and a VL comprising CDRs comprising the amino acid sequences of SEQ ID NO: 34, 36, and 38, respectively (patented claim 14) and an isolated antibody or antigen-binding fragment thereof comprising a full length VH comprising CDRs comprising the amino acid sequences of SEQ ID NO: 40, 42, and 44, respectively, and a VL comprising the full length VL of 2G10 (SEQ ID NO: 17).
However, the ‘509 patent does not teach methods in which the anti-uPAR antibody is administered to a subject in need thereof to treat or prevent FSGS or to inhibit the activity of uPAR and/or suPAR.
The teachings of Wei, with respect to administering an anti-uPAR antibody to treat FSGS, are recited in the 35 U.S.C. § 103 rejection above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to administer the anti-uPAR antibody taught in the ‘509 patent in the method of treating or preventing FSGS or of inhibiting uPAR and/or suPAR activity taught by Wei, comprising administering to a subject an effective amount of the neutralizing anti-uPAR antibody. The skilled artisan would have been motivated to do so because Wei discloses that serum uPAR and suPAR levels are higher in FSGS patients and that administering a neutralizing anti-uPAR antibody ameliorates FSGS symptoms in a mouse model. It would have been further obvious to carry out such a method in a subject who has undergone a kidney transplant and is at risk of recurrent FSGS (relevant to claims 26, 30, and 34), since Wei teaches that the subset of FSGS patients who developed recurrent FSGS after kidney transplant were those who displayed higher levels of serum suPAR before kidney transplant and one year after the transplant. In addition, it would have been obvious to try administering a neutralizing anti-uPAR antibody either prior to, at the time of, or following the kidney transplant (relevant to claims 27-29), to arrive at an optimal treatment regimen through the process of routine optimization. This is because Wei teaches that FSGS patients generally have higher levels of suPAR relative to both healthy controls and other patients with glomerular kidney disease, and furthermore, that those patients who had the highest risk of recurrent FSGS were those with increased serum suPAR before transplant and one year afterward. Presumably, said patients would also have had heightened levels of suPAR at the time of the transplant. Wei demonstrates that suPAR levels are heightened at multiple timepoints in FSGS patients, and that neutralization of suPAR levels is a result-effective variable that ameliorates FSGS symptoms based on data in mouse models. Furthermore, there are a finite number of timeframes at which a potential treatment may be administered to a patient relative to kidney transplant, and one of ordinary skill in the art has good reason to pursue known options within his or her technical grasp.
There would have been a reasonable expectation of success because the anti-uPAR antibody described in the ‘509 patent claims is a functional equivalent of the neutralizing antibody described by Wei and reduces binding of uPAR to its ligand uPA.
Claims 21-26 and 30-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 14-15 of U.S. Patent No. 9,029,509 (supra) in view of Reiser (WO 2010/054189 A1; supra).
The teachings of the ‘509 patent are recited in the non-statutory double patenting rejection above.
However, the ‘509 patent does not teach methods in which the anti-uPAR antibody is administered to a subject in need thereof to treat or prevent FSGS or to inhibit the activity of uPAR and/or suPAR.
The teachings of Reiser, with respect to administering an anti-uPAR antibody to treat FSGS, are recited in the 35 U.S.C. § 103 rejection above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to administer the anti-uPAR antibody described in the ‘509 patent in the method of treating/preventing FSGS or of inhibiting uPAR activity disclosed by Reiser, comprising administering to a subject an effective amount of an anti-uPAR antibody. The skilled artisan would have been motivated to do so because Reiser teaches that uPAR signaling in podocytes is causative of glomerular disease and that inhibition of uPAR has promise in treating proteinuria-associated renal diseases such as FSGS. Furthermore, patients at risk of developing recurrent FSGS have higher serum suPAR levels pre-kidney transplant than non-recurrent FSGS patients and healthy individuals. There would have been a reasonable expectation of success because the anti-uPAR antibody described in the ‘509 patent is a functional equivalent of the inhibitory antibody described by Reiser and reduces binding of uPAR to its ligand uPA.
Claims 21 and 27-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 14-15 of U.S. Patent No. 9,029,509 (supra) in view of Reiser (WO 2010/054189 A1; supra) as applied to claims 1-7 and 11-17 above, further in view of Wei (Nature Medicine (2011) 17: 952-960; supra).
The teachings of the ‘509 patent are recited in the non-statutory double patenting rejection above.
However, the ‘509 patent does not teach methods in which the anti-uPAR antibody is administered to a subject in need thereof to treat or prevent FSGS prior to, at the time of, or following kidney transplant.
The teachings of Reiser and Wei are recited in the 35 U.S.C. § 103 rejections above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to try administering an anti-uPAR antibody such as that taught in the ‘509 patent in the method of treating or preventing FSGS taught by Reiser, comprising administering to a subject an effective amount of the anti-uPAR antibody either prior to, at the time of, or following kidney transplant, to arrive at an optimal treatment regimen through the process of routine optimization. This is because Reiser and Wei teach that FSGS patients who are most at risk of recurrent FSGS after transplant have higher levels of serum suPAR compared to nonrecurrent patients prior to transplant, and Wei further teaches that recurrent FSGS patients also have elevated serum suPAR levels one year after transplant. Presumably, said patients would also have had heightened levels of suPAR at the time of the transplant. Because Wei demonstrates that suPAR levels are heightened at multiple timepoints in FSGS patients, and that neutralization of suPAR levels is a result-effective variable that ameliorates FSGS symptoms based on data in mouse models, it would have been obvious to try treating said patients at multiple time points to determine the most effective treatment regimen. Furthermore, there are a finite number of timeframes at which a potential treatment may be administered to a patient relative to kidney transplant, and one of ordinary skill in the art has good reason to pursue known options within his or her technical grasp. There would have been a reasonable expectation of success because the anti-uPAR antibody taught in the ‘509 patent is a functional equivalent of the inhibitory antibody described by Reiser and reduces binding of uPAR to its ligand uPA.
Response to Arguments (Combined)
Applicant's arguments filed October 8, 2025, with respect to the rejections of record under the judicially created doctrine of non-statutory double patenting, have been fully considered but they are not persuasive.
Applicant submits that the teachings of Wei and Reiser did not provide a reasonable expectation of success in using the claimed antibody for treating or preventing FSGS because the role of suPAR in FSGS was unclear, for the reasons enumerated in response to the rejections under 35 U.S.C. § 103 above.
These arguments are not found convincing for the reasons enumerated in the Response to Arguments above.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643