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 .
Status of the Application
This Office Action is in response to applicant’s arguments filed on 12/15/25. Claims 1-20 are pending. Claims 1-2, 9-10, 12-13, 17-18 have been amended. Claims 1-20 are examined herein.
The claim amendments have rendered the 102 rejection of the last Office Action moot, therefore hereby withdrawn.
Applicant’s arguments with respect to the 103 rejection have been fully considered but found not persuasive, therefore maintained for reasons of record and repeated below for Applicant’s convenience.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (“Kidney as modulator and target of “good/bad” HDL,” Pediatric Nephrology, 2019, 34, 1683-1695, of record and published online on 10/5/18) in view of Roberts et al. (US Patent Application 2012/0157501, of record).
The instant claims are directed to a method of treating proteinuric kidney injury in a subject in need thereof by administering a compound of formula I, wherein R is CR2.
Zhong teaches a method of treating proteinuric kidney injury (pg 6, para 3 to pg 7, para 1, proteinuric patients and animal models; pg 12, para 1). In vivo, proteinuric mice treated with pentylpyridoxamine (PPM) showed significantly reduced urinary excretion of IsoLG, reduction in albuminuria and decrease in urinary KIM-1, together with significant reduction in lymphangiogenesis, comprising: identifying a subject in need of treatment of kidney damage (pg 12, para 1, proteinuric mice; pg 12, para 2, renal injuries that are accompanied by proteinuria (taken as an indicator of disruption in the glomerular filtration barrier)); and administering to said subject an effective isoLG scavenging compound of the formula specified in the claim, wherein R is N; R2 is independently selected from C1-alkyl and C5-alkoxy; and wherein R3 and R4 are each H (pg 12, para 1), modification of aboAVHDL with PPM, a reactive aldehyde scavenger which interacts with IsoLG nearly 2000-times faster than IsoLG reacts with lysine on apoAl. Zhong teaches that the proteinuric kidney injury is damage from kidney disease (pg 3, para 3, CKD; pg 6, para 3 to pg 7, para 1). Zhong also teaches that the damage is to the intestinal lymphatic network (pg 12, para 2), appearance of modified apoAl/HDL in the filtrate (predicted by the CKD setting) enhances the tubular uptake of potentially harmful lipoproteins which activates tubular and interstitial cells, particularly lymphatic endothelial cells that may initiate and perpetuate damaging response in the kidneys. Zhong teaches that the damage is increased contractions of lymphatic vessels and activated lymphatic endothelial cells (pg 12, para 2), appearance of modified apoAl/HDL in the filtrate (predicted by the CKD setting) enhances the tubular uptake of potentially harmful lipoproteins which activates tubular and interstitial cells, particularly lymphatic endothelial cells that may initiate and perpetuate damaging response in the kidneys. Zhong teaches that the damage is disruptions in lymph transport and lymphatic vessel integrity (pg 11, para 3; pg 21, Figure 3; pg 12, para 2).
However, Zhong et al. fail to teach a compound of formula I, wherein R is CR2.
Roberts teaches a compound where R is CR2 since R2, R3 and R4 are H (Figure 46, salicylamine) as an isoLG scavenger (para 0017), Originally, the present inventors called these products solevugliandins to emphasize their similarity to the cyclooxygenase-derived Y-ketoaldehydes, levuglandins E and D...subsequently referred to as isomeric ketoaldehydes, shortened to isoketals (IsoKs)) comparable in isoLG scavenging efficacy to pentylpyridoxamine (PPM) (para 0081, Figure 46 B), and useful in the treatment of disorders that require isoLG-adduct suppression (para 0087-0088).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the claimed invention, to have either combined salicylamine and PPM or substituted salicylamine for PPM.
A person of ordinary skill in the art would have been motivated to make this combination or substitution because both are directed to isoLG scavenging compounds and are disclosed in Roberts et al. Therefore, the skilled artisan would have had a reasonable expectation of success with salicylamine or a combination of salicylamine and PPM to enhance the efficacy of said method toward reducing plasma isoLG level in the treated subject and thereby enhance its efficacy toward treating proteinuric kidney injury in said subject.
Response to Arguments
Applicant argues that there is no motivation to combine Zhong with Roberts. Absent impermissible hindsight reconstruction, one would not look to Roberts for alternative compounds for Zhong. Roberts fails to disclose or suggest modification of apoAI/HDL. There is nothing in Zhong to suggest the use of a compound to treat a wide variety of diseases associated with oxidative injury. Roberts’ disclosure of generic compounds for a broader oxidative damage use does not provide the missing motivation to apply the compounds of Roberts to Zhong’s “modification of apoAI/HDL.”
This is not persuasive because the motivation to combine or substitute salicylamine for PPM does not have to do with apoAI/HDL or oxidative injury. Rather, the reason comes from their functional equivalency as known isoLG scavenging compounds. Therefore, the skilled artisan would have had a reasonable expectation of success with salicylamine or a combination of salicylamine and PPM to enhance the efficacy of said method toward reducing plasma isoLG level in the treated subject and thereby enhance its efficacy toward treating proteinuric kidney injury in said subject.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Conclusion
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 Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam Milligan, can be reached at (571)-270-7674. The fax phone number for the organization where this application or proceeding is assigned is (571)-273-8300.
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/Yong S. Chong/Primary Examiner, Art Unit 1623
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