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 .
Election/Restrictions and
Status of the Claims
2. Applicant’s election without traverse of the following species: 1) the AKR1A1 inhibitor imirestat; 2) acute kidney injury with sepsis; and 3) NAD+ precursor nicotinamide (NAM) in the reply filed on January 5, 2026, is acknowledged with appreciation. In this reply, claims 2, 3, 7, 9, 14, 20, 21 are canceled, and claims 1, 4-6, 10-13, 15-19, and 22 are amended. Claim 24 is newly added.
3. Regarding the scope of the examined invention, the Office has reviewed the claims and disclosure to determine the scope of the independent invention encompassing the elected compound, as follows:
a method of preventing or treating acute kidney injury is associated with sepsis or a renal ischemia reperfusion injury in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the AKR1A1 inhibitor imirestat.
4. The remaining non-elected species are currently withdrawn from consideration, pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, there being no allowable generic or linking claim, i.e., claims 10, 11, 15-19 and 24 are withdrawn.
5. Claims 1, 4-6, 8, 12, 13, 22 and 23 are under examination with the elected species and are the subject of this office action.
Priority
6. The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed provisional application, Application No. 62/689,416, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Application No. 62/689,416 does not have support for the recited limitation(s) of preventing or treating acute kidney injury, comprising administering the AKR inhibitor imirestat to the subject. Therefore Applicant’s instant claims are afforded benefit of priority to Application PCT/US2019/038982, filed June 25, 2019.
Specification
7. Applicant is reminded of the proper content of an abstract of the disclosure.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
8. The abstract of the disclosure is objected to because the claimed method is limited to preventing or treating acute kidney injury, and the compound is limited to a selective or partially selective AKR1A1 inhibitor. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 112
9. 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.
10. Claims 1, 4-6, 8, 12, 13, 22 and 23 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.
11. In particular, support cannot be found for the full scope of AKR1A1 inhibitors as instantly claimed.
12. The MPEP §2163 states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. In the case of chemical entities, Applicant's attention is further directed to Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), which notes that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, “not a mere wish or plan for obtaining the claimed chemical invention.” While the court recognizes that, “[i]n claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass” (Id.), it is also recognized that for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim and/or the genus must be sufficiently detailed to show that applicant was in possession of the claimed invention as a whole (see Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555 (Fed. Cir. 1991)). If a genus has substantial variance, the disclosure must present a sufficient number of representative species that encompass the genus in order to adequately describe the genus (i.e., the disclosure must describe a sufficient variety of species to reflect the variation within that genus). See MPEP § 2163. Otherwise, as stated by the court in Ariad Pharmaceuticals, Inc., v. Eli Lilly and Company (Fed. Cir. 2010), “a generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus. The problem is especially acute with genus claims that use functional language to define the boundaries of a claimed genus, i.e., “selective or partially selective AKR1A1 inhibitor.” In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the Applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.”
13. In the instant case, it is evident that the genus of compounds embraced by “selective or partially selective AKR1A1 inhibitor” has substantial variance. The genus is virtually without limit, embracing hundreds of millions of potential compounds bearing no structural resemblance to one another what-so-ever. Yet, the instant Specification fails to disclose the preparation or administration of any compound species, including imirestat and “analogues thereof.” While the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number of species to adequately describe a broad generic. For example, in In re Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d 1008 (Fed. Cir. 1989). In the instant case, it is similarly determined that the instant disclosure does not adequately describe a subgenus embracing hundreds of millions of additional compound species bearing no structural relationship. That is, the Specification does not disclose a sufficient variety of species to reflect the extreme variance in the genus.
14. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate”). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
As such, claims 1, 4- 6, 8, 12, 13, 22 and 23 are rejected.
15. Claims 1, 4-6, 8, 12, 13, 22 and 23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating acute kidney injury as a result of ischemia reperfusion injury by inhibiting AKR1A1, comprising administering the elected compound species and those embodied by the instant Specification, is not considered enabled for preventing or treating acute kidney injury comprising administering any/ all selective AKR1A1 inhibitor(s). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
16. The standard for determining whether the Specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), that is still the standard to be applied, determined by consideration of the Wands factors (MPEP 2164.01(A)); namely, nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered, with the most relevant factors discussed below:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
17. These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons.
18. Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
In the instant case, the claims are drawn to a method of preventing or treating acute kidney injury in a subject in need thereof, comprising: administering to the subject any AKR1A1 inhibitor.
19. The state of the prior art, level of predictability and relative skill level: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.”
As discussed above, the instantly claimed invention pertains to a method of preventing or treating acute kidney tissue injury in a subject in need thereof, comprising: administering to the subject any AKR1A1 inhibitor.
20. The relative skill of those in the art is high, that of an MD or PhD. That factor is outweighed, however, by the unpredictable nature of the art. As illustrative of the state of the art, modifying even a single atom in a compound can dramatically change the compound’s overall structure and - even though complementarity in one portion of the compound might be improved by the chemical revision - the overall binding or activity might be severely compromised. This is certainly true in the case of aldo-keto reductase (AKR) inhibitors which, as disclosed by Penning, embrace a vast scope of 16 AKR families, including AKR1A1 (aldehyde reductase). However, Penning (Chemico-Biological Interactions 2015) teaches that AKR inhibitors have demonstrated significant unpredictability in research and development: “Isoform specific inhibitors of the human enzymes are required to target specific diseases with the understanding that off-target effects may occur when these compounds bind to related AKRs; a lack of appreciation for the similarity in AKR structure– function could lead to the failure of therapeutic leads.” (see abstract; page 238, left column, first paragraph; and page 244, right column, last paragraph).
21. The amount of direction or guidance provided and the presence or absence of working examples: The amount of direction provided by the Applicant is considered to be determined by the Specification and the working examples. In the instant case, the specification provides no direction or guidance for the use of all of the aforementioned inhibitors in treating any/all tissue injury “associated with ischemia reperfusion injury.” No reasonably specific guidance is provided concerning useful therapeutic protocols for said disclosed compounds, other than Imirestat …
22. Applicant demonstrate in the specification, Example at pages 70-86, that knockout SCoR-/- and/or PKM2 mice had greater renoprotection against acute kidney injury, however the Specification is silent to the administration of any inhibitor of AKR1A1 for the actual prevention or treatment of acute kidney injury. Because genetic silencing completely ablates the gene while pharmacological inhibition may still cause interaction of said protein with other co-binding partners, no real conclusion can be made as to the effectiveness of the protein inhibition of SCoR with respect to treating, let alone preventing, acute kidney injury. Applicant has not demonstrated that any inhibitor of AKR1A1 shows efficacy for treating, let alone preventing, any type of acute kidney injury, in vitro or in vivo.
23. The breadth of the claims: As stated in MPEP 2164.01(c), “[w]hen a compound or composition claim is limited by a particular use, enablement of that claim should be evaluated based on that limitation.” Thus, as stated in MPEP 2164.08, “[t]he focus of the examination inquiry is whether everything within the scope of the claim is enabled” (emphasis added). Indeed, the Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright, 999 F.2d 1557 (Fed. Cir. 1993) (emphasis added). At the same time, however, it is also recognized that not everything necessary to practice the invention need be disclosed. Nor is it necessary that an Applicant test all the embodiments of his invention. In re Angstadt, 537 F.2d 498 (CCPA 1976) (emphasis added). In fact, as stated by the court in In re Buchner, 929 F.2d 660 (Fed. Cir. 1991), a patent need not teach, and preferably omits, what is well known in the art.
24. Accordingly, for purposes of enablement, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate in scope with the protection sought by the claims. Thus, while “a patent application is entitled to claim his invention generically” it is necessary that “he provide a disclosure sufficient to enable one skilled in the art to carry out the invention commensurate with the scope of his claims". Amgen, In.c, v. Chugai Pharmaceutical Co., Ltd. (Fed. Cir. 1991). As noted by the court in In re Fisher, 427 F.2d 833 (CCPA 1970), the scope of enablement must bear a “reasonable correlation” to the scope of the claims. See also Ak Steel Corp. v. Sollac, 344 F.3d 1234 (Fed. Cir. 2003) and In re Moore, 439 F.2d 1232 (CCPA 1971). As stated in MPEP 2164.08, resolution of this concern requires two stages of inquiry: “[t]he first is to determine how broad the claim is with respect to the disclosure. The entire claim must be considered. The second inquiry is to determine if one skilled in the art is enabled to make and use the entire scope of the claim without undue experimentation”.
25. As to the first inquiry, as discussed above, the claims are thus very broad insofar as they are directed to the prevention or treatment of any type of acute kidney injury in a subject in need thereof, comprising: administering to the subject any compound that is considered an AKR1A1 inhibitor. While such “treatment” might theoretically be possible utilizing Imirestat or the Imirestat analogue delineated in Fig. 6, as a practical matter it is nearly impossible to achieve treatment for said disease with every possible alternative AKR1A1 inhibitor, let one prevention.
26. Considering that the scope of said inhibitors encompasses thousands of compound species, and potentially hundreds of thousands of compound species, it is evident that the claims are broad. Yet, as discussed above, the instant Specification discloses only one working example of acute kidney injury in knockout SCoR -/- and/or PKM2 mice (pages 70-86), but do not disclose the administration of any AKR1A1 inhibitor whatsoever. As such, the claim is extremely broad with respect to the disclosure. The second inquiry is discussed in detail below.
27. The amount of experimentation necessary: In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the invention as claimed. As discussed above, the claims are drawn to a method of preventing or treating any/ all kinds of acute kidney injury in a subject in need thereof, comprising: administering to the subject any AKR1A1 inhibitor.
28. Since identifying any compound which is capable of modulating the activity of a specific receptor, ion channel, or enzyme is extremely complex, the nature of the instant invention considered to be one of extreme complexity. In the instant case, this complexity is exacerbated by the broadness of any AKR1A1 inhibitor with respect to the disclosure since the scope of said inhibitors encompasses thousands of compound species, and potentially hundreds of thousands of compound species, whereas the instant Specification fails to disclose the administration of any such compound species exerting the disclosed activity. Although the relative skill of those in the art to which the invention pertains is high, the state of the art and unpredictability within the art is such that even the most talented artisan could not reasonably predict which of the hundreds of millions of compounds encompassed by the claims would exert the alleged activity based on the limited disclosure. Although the skilled artisan would have known that certain chemical modifications to the disclosed compounds may predictably provide structurally related compounds having similarly activity, the skilled artisan would have also known that even minor structural changes can, and frequently will, drastically alter or eradicate a parent compound’s ability to modulate the activity of a specific receptor or enzyme. As evidenced by Penning, above, aldo-keto reductase inhibitors, in particular, demonstrate significant unpredictability, i.e., “a lack of appreciation for the similarity in AKR structure– function could lead to the failure of therapeutic leads.” Thus, given the unpredictability of AKRs in particular, it is highly unpredictable whether any inhibitor within the genus of compounds encompassed by the claims based on the instant disclosure would, in fact, be usable. Whether the other compounds encompassed by the claims would be usable is even less predictable. As such, the only way to ascertain which of the thousands, and potentially hundreds of thousands of claimed compounds presently encompassed by the claims are usable based on the limited disclosure would require undue experimentation. That is, the only way one skilled in the art is enabled to use the entire scope of the claim based on the instant disclosure entails undue experimentation.
To overcome this rejection, Applicant should narrow the scope of the claims such that they bear a reasonable correlation with the disclosure, i.e., limit the genus of AKR1A1 inhibitors and delete “preventing” from the claims.
Claim Rejections - 35 USC § 103
29. 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.
30. Claims 1, 4-6, 8, 12, and 13 are rejected under 35 U.S.C. 103(a) as being unpatentable over Stamler, Jonathan, U.S. 20170360755 A1, in view of Zager et al., (Am. J. Physiol. Renal Physiol 2006).
It is noted that the disclosure of the prior-filed provisional application, Application No. 62/689,416, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for the recited limitation(s) of preventing or treating a tissue injury associated with ischemia reperfusion injury in a subject, wherein the tissue injury is acute kidney injury, comprising administering the AKR inhibitor imirestat to the subject. Therefore Applicant’s instant claims are afforded benefit of priority to Application PCT/US2019/038982, filed June 25, 2019.
Claim 1 is directed to a method for preventing or treating acute kidney injury associated with sepsis (claim 12)) in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of selective or partially selective AKR1A1 inhibitor, (more specifically, imirestat:
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), more specifically wherein the AKR1A1 inhibitor is administered at an amount effective to promote S-nitrosylation of proteins in the subject, and wherein the AKR1A1 inhibitor is not an ADH3 inhibitor (claim 13), wherein the method prevents or treats acute kidney injury associated with a renal ischemia reperfusion injury (claim 4).
31. Stamler teaches and recites a method of treating disorders associated with NO/SNO (nitric oxide adducts called S-nitrosothiols or “SNO”) deficiency or benefiting from increased SNO in a subject in need thereof, the method comprising: administering to the subject an AKR inhibitor at an amount(s) effective to promote S-nitrosylation of proteins in the subject, wherein the inhibitor is not ADH3 (see Stamler Claim 1), more specifically wherein the AKR inhibitor is an AKR1A1 inhibitor that is imirestat (see Stamler Claims 2 and 3). Stamler teaches the selectivity for AKR1A1: “the AKR1A1 inhibitor can have a selectivity for AKR1A1 versus AKR1B1≧10 times” and specifically names imirestat as the selective or partially selective AKR1A1 inhibitor (see paragraphs [0084]-[0085]).
32. Stamler goes on to teach that the method can be used to treat ischemic-reperfusion injury and specifically names renal ischemia (paragraphs [0149] and [0151]).
33. Stamler is silent to the prevention or treatment of acute kidney injury in said subject.
34. However, Zager et al. suggest that acute renal failure (aka acute kidney injury) is characterized by excess iNOS activity/protein nitrosylation (See abstract). Zager et al. teach that NO hyperproduction with increased protein nitrosylation appears to be concomitant with acute renal failure (page F555, left column, second paragraph). As such, one skilled in the art before the effective filing date of the claimed invention would reasonably consider that by virtue of administering the selective AKR1A1 inhibitor imirestat, which promotes S-nitrosylation of proteins in the subject, one is necessarily treating acute kidney injury in said subject. It would have been obvious to one of skill in the art before the effective filing date of the claimed invention to administer the selective AKR1A1 inhibitor imirestat to a subject in need thereof to treat acute kidney injury associated with renal ischemic-reperfusion injury in said subject.
Thus, claims 1, 4, 12 and 13 are prima facie obvious.
Claim 5 is drawn to claim 1, and limits wherein the amount of AKR1A1 inhibitor, administered to the subject is an amount effective to induce renal vasodilatation, enhance resistance to hypoxia, improve renal hemodynamics, decrease renal oxidative stress, reduce renal inflammation, and/or preserve renal function.
35. Stamler additionally teaches other conditions or disorders associated with ischemia that are “suitable for treatment or amelioration using the methods described herein” including renal ischemia, inflammation, hypoxia, ischemic renal disease, and vascular disease of the kidney. Thus, by virtue of administering the selective AKR1A1 inhibitor to a subject, one of skill in the art before the effective filing date of the claimed invention would reasonably expect a reduction in renal inflammation, and/or a preservation of renal function in said subject.
As such, claim 5 is prima facie obvious.
Claim 6 is drawn to claim 1 and limits wherein the AKR1A1 inhibitor is administered before and/or after the ischemia reperfusion injury.
Claim 8 is drawn to claim 1, wherein the AKR1A1 inhibitor is administered at least about 2 hours before and/or at least about 30 minutes after acute kidney injury.
36. Stamler teaches that the AKR1A1 inhibitor can be administered before or after onset of the unwanted condition, disease, or unwanted state:
“[i]f it is administered prior to clinical manifestation of the unwanted condition (e.g., disease or other unwanted state of the host animal) then the treatment is prophylactic, i.e., it protects the host against developing the unwanted condition, whereas if it is administered after manifestation of the unwanted condition, the treatment is therapeutic,”
(paragraph 0053]). And, dose regimen optimization is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize given the guidance of the prior art. Thus it would have been obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize a parameter of a known method, i.e., timing of administration such that the AKR1A1 inhibitor is administered several hours prior to acute kidney injury (such as when renal ischemia starts) or about 30 minutes after the onset of renal ischemia, with a reasonable expectation of success.
As such, claims 6 and 8 are prima facie obvious.
Claim 22 is drawn to claim 1, further comprising administering nicotinamide adenine dinucleotide (NAD+) and/or a NAD+ precursor in combination with the selective or partially selective AKR1A1 inhibitor.
Claim 23 is drawn to claim 22, wherein the NAD+ precursor is selected from the group consisting of tryptophan, nicotinic acid, nicotinic acid riboside, nicotinamide riboside (NR), and nicotinamide (NAM).
37. Stamler teaches combining the AKR1A1 inhibitor with an additional agent selected from an ADH inhibitor (paragraph [0157]), and discusses alternative ADH inhibitors in paragraphs [0093]-[0096]. In particular, Stamler discloses the ADH inhibitors isonicotinic acid (a position isomer of nicotinic acid), and CNAD (5-beta-D-ribofuranosylnicotinamide adenine dinucleotide), (i.e., an isomeric and isomeric analogue of NAD), (paragraphs [0093] and [0095]). As the isotonic acid and CNAD compounds are both disclosed as ADH inhibitors and therefore have the same utility as the recited nicotinic acid and nicotinamide adenine dinucleotide (NAD+), respectively, and are generally sufficiently similar in structure, there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril). Thus one of skill in the art before the effective filing date of the claimed invention would have been motivated to combine said either of said ADH inhibitors with imirestat in the method of treatment disclosed by Stamler, because one would have reasonably expected that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979).
As such, claims 22 and 23 are prima facie obvious.
Double Patenting
38. 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).
39. 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).
40. 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.
41. 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.
42. Claims 1, 4, and 13, are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 7 of U.S. Patent No. 11,351,155 B2 in view of Zager et al., (Am. J. Physiol. Renal Physiol 2006).
Instant claim 1 is directed to a method for preventing or treating acute kidney injury in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of selective or partially selective AKR1A1 inhibitor, (more specifically, imirestat:
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), (more specifically wherein the AKR1A1 inhibitor is administered at an amount effective to promote S-nitrosylation of proteins in the subject, and wherein the AKR1A1 inhibitor is not an ADH3 inhibitor (claim 13)), wherein the method prevents or treats acute kidney injury associated with a renal ischemia reperfusion injury (claim 4).
43. U.S. Pat. No. 11,351,155, CLAIM 1 recites a method of treating disorders associated with NO/SNO (nitric oxide adducts called S-nitrosothiols or “SNO”) deficiency or benefiting from increased SNO in a subject in need thereof, the method comprising: administering to the subject an AKR1A1 inhibitor at an amount(s) effective to promote S-nitrosylation of proteins in the subject, wherein the disorder comprises renal ischemia. CLAIM 2 is drawn to claim 1 and limits wherein the AKR inhibitor is imirestat. CLAIM 3 is drawn to claim1 and limits the selectivity for AKR1A1: “the AKR1A1 inhibitor can have a selectivity for AKR1A1 versus AKR1B1≧10 times” and specifically names imirestat as the selective or partially selective AKR1A1 inhibitor. CLAIM 4 is drawn to claim 1 and limits the disorder to renal ischemia.
CLAIM 7 recites a method of treating disorders associated with NO/SNO deficiency or benefiting from increased SNO in a subject in need thereof, the method comprising: administering to the subject an AKR1A1 inhibitor at an amount(s) effective to promote S-nitrosylation of proteins in the subject, wherein the AKR1A1 inhibitor is imirestat and wherein the disorder comprises renal ischemia.
44. U.S. Pat. No. 11,351,155 does not recite the prevention or treatment of acute kidney injury in said subject.
45. However, Zager et al. suggest that acute renal failure (aka acute kidney injury) is characterized by excess iNOS activity/protein nitrosylation (See abstract). Zager et al. teach that NO hyperproduction with increased protein nitrosylation appears to be concomitant with acute renal failure (page F555, left column, second paragraph). As such, one skilled in the art before the effective filing date of the claimed invention would reasonably consider that by virtue of administering the selective AKR1A1 inhibitor imirestat, which promotes S-nitrosylation of proteins in the subject, one is necessarily treating acute kidney injury in said subject. It would have been obvious to one of skill in the art before the effective filing date of the claimed invention to administer the selective AKR1A1 inhibitor imirestat to a subject in need thereof to treat acute kidney injury associated with renal ischemic-reperfusion injury in said subject.
Thus, claims 1, 4, and 13 are prima facie obvious over claims 1-4 and 7 of U.S. Pat. No. 11,351,155.
Conclusion
46. In conclusion, claims 1, 4-6, 8, 10-13, 15-19, and 22-24 are pending in the application. Claims 10, 11, 15-19 and 24 are presently withdrawn from consideration. Claims 1, 4-6, 8, 12, 13, 22 and 23 are rejected. No claim is currently allowable.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628