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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/10/2026, has been entered.
Claims 10, 16, 17, 19, 20, and 22 are pending.
Claims 10, 19, 20, and 22 are currently amended.
Claims 10, 16, 17, 19, 20, and 22 are under examination on the merits.
Rejections Maintained
35 U.S.C. 103
The rejection of claims 10, 16, 17, 19, 20, and 22 under 35 U.S.C. 103 as being unpatentable over Hashimoto et al. (US PG PUB 2018/0100012, publication date: 04/12/2018) in view of Lincoln et al. (Tzu Chi Medical Journal, 20(3): 161-168, 2008) and Issar et al. (Clinical Neurophysiology, 130: 2088-2095, 2019) is maintained.
Nonstatutory Double Patenting
The rejection of claims 10, 16, 17, 19, 20, and 22 on the ground of nonstatutory double patenting as being unpatentable over 1) claim 1 of U.S. Patent No. 10,287,346 and 2) claim 1 of US PAT 11,008,388 in view of Hashimoto et al. (US PG PUB 2018/0100012, publication date: 04/12/2018), Lincoln et al. (Tzu Chi Medical Journal, 20(3): 161-168, 2008), and Issar et al. (Clinical Neurophysiology, 130: 2088-2095, 2019) is maintained.
The provisional rejection of claims 10, 16, 17, 19, 20, and 22 on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/322,482 in view of Hashimoto et al. (US PG PUB 2018/0100012, publication date: 04/12/2018), Lincoln et al. (Tzu Chi Medical Journal, 20(3): 161-168, 2008), and Issar et al. (Clinical Neurophysiology, 130: 2088-2095, 2019) is maintained.
Response to Arguments
In Applicant Arguments, dated 06/10/2026, Applicant asserts that “Lincoln et al. contains no disclosure whatsoever regarding RGMa, which is the central target of the present invention as defined by the pending claims. More importantly, Lincoln et al. contains no description of nerve degeneration or neuronal cell death in the kidney. The passage at pages 162-163 of Lincoln et al. cited by the Office describes degenerative changes only in the sympathetic nerves supplying the small intestine and ileum, including the celiac ganglion/superior mesenteric ganglion (CG/SMG) and the myenteric plexus...” Applicant asserts that said passage relates to the gastrointestinal autonomic nervous system but not the renal autonomic nervous system.
These arguments have been fully considered but are not deemed sufficient to overcome the rejection of the claims under 35 U.S.C. 103. Lincoln et al. provide multiple teachings that relate to the renal autonomic nervous system. For example at p. 162 and 163, Lincoln et al. suggest that diabetes leads to degenerative changes in autonomic nerves, including features of axonopathy, which is a characteristic feature of DAN - “These features reflect the dying back type of distal axonopathy that is generally held to be the characteristic feature of diabetic autonomic neuropathy [DAN].” Furthermore at p. 163, Lincoln et al. suggest that the neuronal cell death and loss of autonomic neurons that occurs in diabetes is characterized by axonal degeneration. Given that the anti-RGMa antibodies of Hashimoto et al. promote the generation of axons, there would have been a reasonable expectation that said antibodies may be used to reverse or improve the negative characteristics of DAN, thereby providing a therapeutic benefit to DAN patients. Therefore in view of the references cited, at the effective filing date of the invention, it would have been prima facie obvious to treat DAN by administering an effective dose of an anti-RGMa neutralizing antibody.
Applicant further states that “[a] person of ordinary skill in the art reading Issar et al. might therefore be motivated to treat the CKD or the systemic uremic state (e.g., via potassium restriction) in order to alleviate the resulting neuropathy. However, there is nothing in Issar et al. that would have motivated an ordinarily skilled artisan to treat the neuropathy itself as a means of improving kidney function.”
These arguments have been fully considered but are not deemed persuasive. At [0034], Hashimoto et al. teach that anti-RGMa neutralizing antibodies of the invention may be used to treat diabetes mellitus. At [0036], Hashimoto et al. teach 1) an anti-RGM neutralizing antibody that comprises the LCDRs 1-3 and the HCDRs 1-3 of SEQ ID NO(s): 30-35, respectively, and these CDRs share 100% sequence homology with the instant SEQ ID NO(s): 5-10, respectively, corresponding to (a) of claim 10, and 2) an anti-RGM neutralizing antibody that comprises the LCDRs 1-3 and the HCDRs 1-3 of SEQ ID NO(s): 36-40 and SFG, respectively, and these CDRs share 100% sequence homology with the instant SEQ ID NO(s): 11-15 and SFG, respectively, corresponding to (b) of claim 10. Furthermore Lincoln et al. suggest that axonopathy and axonal degeneration are characteristics of DAN. Given that the anti-RGMa antibodies of Hashimoto et al. promote the generation of axons, there would have been a reasonable expectation that said antibodies may be used to reverse or improve the negative characteristics of DAN, thereby providing a therapeutic benefit to DAN patients. Additionally Issar et al. suggest that neuropathy may be more severe in DKD patients. As such one of ordinary skill in the art would have been motivated to practice the method of Hashimoto et al. and Lincoln et al. on patients having diabetic neuropathy, such as DAN, with associated DKD, because said patients likely have an increased need for relief from neuropathy. The invention of Hashimoto et al., Lincoln et al., and Issar et al. functions by the same mechanism as the claimed invention, specifically, an anti-RGMa antibody is used to treat neuropathy in the kidney, thereby improving kidney disfunction.
Applicant further asserts that the “discovery - that treating local neuropathy within the kidney leads to an improvement in kidney dysfunction… - is entirely contrary to the teaching of Issar et al. The disclosure of Issar et al. therefore teaches away from the present invention as defined by the pending claims rather than providing any motivation to arrive at the present invention. Therefore, the Office’s position that ‘the invention of Hashimoto et al., Lincoln et al., and Issar et al. functions by the same mechanism as the claimed invention, specifically, an anti- RGMa antibody is used to treat neuropathy in the kidney, thereby improving kidney dysfunction’ is not correct. Neither Hashimoto et al., Lincoln et al., nor Issar et al. discloses or suggests the critical mechanism disclosed in the present application: the local upregulation of RGMa in the kidney under diabetic conditions and its causal link to kidney dysfunction via local autonomic nerve degeneration. This causal linkage is the core discovery of the present application, and its recognition is possible only with the benefit of hindsight knowledge derived from the present specification.”
These arguments have been fully considered but are not deemed persuasive. According to MPEP 2145(X)(A). “Applicants may argue that the examiner’s conclusion of obviousness is based on improper hindsight reasoning. However, ‘[a]ny judgment on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper.’ In re McLaughlin, 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971).” As discussed above the instant claims were prima facie obvious at the time of the invention in view of the references cited. The finding that the instant claims were prima facie obvious at the time of the invention is based upon the teachings of the prior art, not based on knowledge gleaned only from Applicant’s disclosure. The claim rejections under 35 U.S.C. 103(a) are properly based on the teachings of the prior art and the general understanding of one of ordinary skill in the art, and as such Applicant’s argument that the rejection of the claims under 35 U.S.C. 103 is based upon improper hindsight reasoning is not persuasive.
Furthermore even if the critical mechanism of the disclosed application is the local upregulation of RGMa in the kidney under diabetic conditions and its causal link to kidney dysfunction via local autonomic nerve degeneration, the rejection of the claims under 35 U.S.C. 103 is still appropriate, because the upregulation of RGMa in the kidney is not an element of the claims. In other words the claims do not require measuring RGMa expression in the kidneys. As indicated above given that the anti-RGMa antibodies of Hashimoto et al. promote the generation of axons, there would have been a reasonable expectation that said antibodies may be used to reverse or improve the negative characteristics of DAN (axonopathy and axonal degeneration), thereby providing a therapeutic benefit to DAN patients. Additionally Issar et al. suggest that neuropathy may be more severe in DKD patients. As such one of ordinary skill in the art would have been motivated to practice the method of Hashimoto et al. and Lincoln et al. on patients having diabetic neuropathy, such as DAN, with associated DKD, because said patients likely have an increased need for relief from neuropathy. Lastly in the absence of evidence to the contrary, one of ordinary skill in the art would reasonably expect that the anti-RGMa antibodies of Hashimoto et al. are capable of binding RGMa that is expressed in effectively any organ, including the kidney. The claim rejections under 35 U.S.C. 103 are maintained.
Given that the claim rejections under 35 U.S.C. 103 are maintained, the obviousness-type double patenting rejections of record have also been maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F 9:00 am - 6:00 pm EST
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached on 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
Prosecution Insights