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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 13, 2026 has been entered.
Application Status
The amended claims filed April 13, 2026 with the Request for Continued Examination are acknowledged. Claim 21 has been amended. Claims 34-38 are newly added.
Claims 21-38 are pending and under examination herein.
WITHDRAWN OBJECTIONS
The prior grounds of objection to claims 21-29 are withdrawn in view of Applicant's amendments to claim 21.
MAINTAINED REJECTIONS AND NEW REJECTIONS NECESSITATED BY CLAIM AMENDMENT
Claim Objections (New)
Claims 21-38 are objected to for the following informalities: For consistency of formatting, claims 21 and 30 should recite “; and” after the sequence of the VH CDR2.
Appropriate correction is required.
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.
(1)
Claims 21-38 are rejected under 35 U.S.C. 103 as being unpatentable over Wei (Nature Medicine (2011) 17: 952-960; cited in PTO-892) in view of Craik (US 9,029,509 B2; cited in PTO-892). This is a maintained rejection that has been updated to reflect Applicant's claim amendments.
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 (e.g., 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 (e.g., Introduction). Wei investigated in mouse models whether suPAR causes or is caused by FSGS, and observed that suPAR induced FSGS phenotypes (e.g., Results, pages 956-958; Figures 4-5). Relevant to claims 21, 23-24, 30, and 32-38, 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 (e.g., 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 (e.g., Results, page 957). Subjects with FSGS would be expected to be candidates for kidney transplant, further relevant to claim 25.
Pertinent to claims 26-30 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 (e.g., 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 (e.g., 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 (e.g., 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 (e.g., 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 (e.g., 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 (e.g., 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 FSGS, preventing recurrent FSGS or inhibiting uPAR and/or suPAR activity taught by Wei. 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.
(2)
Claims 21-26 and 30-38 are rejected under 35 U.S.C. 103 as being unpatentable over Reiser (WO 2010/054189 A1; cited in PTO-892) in view of Craik (US 9,029,509 B2; supra). This is a maintained rejection that has been updated to reflect Applicant's claim amendments.
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 34-38. 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. 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.
(3)
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 30-38 above, further in view of Wei (Nature Medicine (2011) 17: 952-960; supra). This is a maintained rejection that has been updated to reflect Applicant's claim amendments.
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 combined arguments filed April 13, 2026, with respect to the rejections of record under 35 U.S.C. § 103, have been fully considered but they are not persuasive.
Applicant argues that the cited references teach away from the instantly claimed invention “because Wei teaches that interfering with the suPAR-β3 integrin interaction is required for an anti-uPAR antibody to treat FSGS and Craik teaches that the 2G10 antibody which has the same CDRs as the antibody recited in the present claims does not disrupt uPAR-mediated integrin adhesion”, citing Wei (see Abstract; page 957) and Craik (see cols 77-79) for support. Remarks at pages 7-8. Applicant also states that “since Craik does not teach or suggest that the 2G10 antibody can interfere with the suPAR-β3 integrin interaction, the POSITA would have no reason to use the 2G10 antibody in the claimed method”. Remarks at page 8.
In response, it is held that the cited references do not teach away from the claimed invention for at least the following reasons. It is noted that Craik (at Example 10, cols 78-79) investigated whether the anti-uPAR antibodies of the invention interfere with the interaction of uPAR and β1-integrin, which is distinct from the β3-integrin described by Wei. As Applicant points out, “Craik does not teach or suggest that the 2G10 antibody can interfere with the suPAR-β3 integrin interaction” (Remarks at page 8) because Craik investigated whether the anti-uPAR antibodies of the invention interfere with the interaction of uPAR and β1-integrin (see Figure 8). As noted in MPEP § 2145 (II), “[m]ere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention”. It remains held that Wei clearly sets forth that administering an anti-uPAR antibody which interferes with the suPAR-β3 interaction would be suitable for use in treating FSGS, and that a PHOSITA would recognize that an anti-uPAR antibody which inhibits uPAR activity would be expected to interfere with said interaction absent a showing otherwise. This idea is supported by Wei’s observation that administering a neutralizing anti-uPAR antibody ameliorates FSGS-like symptoms in a murine model and by Reiser’s teaching of a method of administering antibodies that inhibit binding of uPAR to its ligand to treat human subjects affected by or at risk of diseases or disorders associated with pathological urokinase receptor molecule expression and/or activity, of which FSGS is one example.
Applicant further submits that at the time of filing, “it was not known whether an antibody that binds to uPAR and suPAR can treat or prevent FSGS in a human subject”, pointing to the teachings of Wei (see paragraph spanning pages 958-959) and Harel (Transplantation (2020) 104(1): 54-60)1 (see Background and Abstract) for support. Remarks at pages 9-10. Applicant argues that at the time of filing, it was “not clear if suPAR is involved in causing FSGS” and further, “which fragment of suPAR, i.e., which domain of suPAR correlates to FSGS and should be targeted”. Remarks at page 10.
In response, it is noted that in contrast to Applicant's assertions, Wei expressly states, “Our study identifies serum suPAR as a circulating factor that may cause FSGS” (Abstract). Even if it was unknown which suPAR domain specifically contributes to its pathogenic strength, the teachings of Wei clearly set forth that suPAR plays a role in FSGS pathology. With respect to the teachings of Harel, inconsistencies in the teachings of Harel as well as reasons acknowledged by Harel that could have contributed to any discordant findings in the literature are discussed in the final Office Action mailed January 12, 2026 (see pages 10-11).
In addition, it is further noted that at least Reiser provides a teaching of using an anti-uPAR/suPAR antibody (e.g., an antibody that inhibits uPAR/suPAR) to treat FSGS in a human subject because 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). Accordingly, based on the teachings of the prior art as a whole, one would have been motivated to administer the 2G10 antibody to treat FSGS because this antibody would have been expected to interfere with uPAR signaling in the disease such that the antibody would have been reasonably expected to treat the disease.
For at least these reasons, the rejections are maintained.
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.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
(1)
Claims 21-38 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) in view of Wei (Nature Medicine (2011) 17: 952-960; supra). This is a maintained rejection that has been updated to reflect Applicant's claim amendments.
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.
(2)
Claims 21-26 and 30-38 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). This is a maintained rejection that has been updated to reflect Applicant's claim amendments.
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.
(3)
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 21-26 and 30-38 above, further in view of Wei (Nature Medicine (2011) 17: 952-960; supra). This is a maintained rejection that has been updated to reflect Applicant's claim amendments.
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 combined arguments filed April 13, 2026, 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 teach away from the claimed invention 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.
Citation of Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Reiser (US 2014/0083945 A1; cited in IDS) discloses, “The present study demonstrates that suPAR is a circulating serum factor that can cause FSGS. This conclusion is based on the human studies that show elevated serum levels of suPAR in a population of pediatric and adult FSGS patients and on animal models with engineered suPAR overexpression that develop a renal disease characteristic of FSGS. High pre-transplantation serum suPAR levels are associated with the presence of native FSGS and also constitute a significantly increased risk for recurrent FSGS after transplantation. One year after kidney transplantation, suPAR levels remain significantly elevated in patients that develop FSGS recurrence. The mechanism of injury caused by FSGS associated suPAR is through activation of β3 integrin on podocytes, an event sufficient to initiate podocyte foot process effacement and proteinuria. The level of podocyte β3 integrin activity that is driven by suPAR depends on the amount of individual serum suPAR and possibly also on suPAR post-translational modification (i.e., glycosylation status), and appears to be independent of total serum uPA levels, which is in contrast to suPAR-uPA associations in some forms of cancer. Thus, interference in pathogenesis by removing suPAR from the circulation can protect a subject from suPAR-mediated podocyte injury. The level of suPAR must be reduced to a level (measured as an absolute amount, concentration in the circulation, or relative amount as compared to another serum protein) sufficient to stop or slow disease pathogenesis by reducing podocyte β3 integrin activity” (¶ 0079).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Elizabeth A Shupe whose telephone number is (703) 756-1420. The examiner can normally be reached Monday to Friday, 9:30am - 6:00pm EST.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643
1 Harel was also cited by the Applicant in the Remarks filed on October 8, 2025 to rebut the rejections under 35 U.S.C. § 103.
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