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
Filing Receipt and Priority
The filing receipt mailed 09/20/2024 states that the instant application is a 371 of PCT/US2022/047380, filed 10/21/2022, which claims benefit of provisional application 63/270,198, filed 10/21/2021.
The instant claims are supported by the provisional disclosure. Therefore, the effective filing date is 10/21/2021.
Information Disclosure Statement
The information disclosure statement (DS) submitted 04/19/2024 has been considered.
Restriction/Species Election
Application’s election of the following is acknowledged.
In the remarks submitted 06/29/2024, applicant elected Group I, claims 1-13. Applicant also elected the following species:
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At examiner’s discretion, search and examination have been broadened to include all species in claim 2.
Rejections
Claim Rejections - 35 USC § 112(a)
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.
Scope of Enablement
Claims 1-7 and 9-13 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 pain using either MaR1 or NPD1 in subjects in need of treatment, does not reasonably provide enablement for prevention of pain and/or treating pain using any GPR37L1 ligand. 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.
The following Wands Factors have been considered if not explicitly discussed: (A) The breadth of the claims, (B) The nature of the invention, (C) The state of the prior art, (D) The level of one of ordinary skill, (E) The level of predictability in the art, (F) The amount of direction provided by the inventor, (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Breadth of the claims
Claim 1 states “A method for treating pain in a subject, the method comprising administering a therapeutically effective amount of a GPR37L1 ligand to the subject.”
“Treatment” is defined in para. [0035] as “the clinical intervention made in response to a disease, disorder or physiological condition (e.g., pain) manifested by a patient or to which a patient may be susceptible. The aim of treatment includes the alleviation or prevention of symptoms, slowing or stopping the progression or worsening of a disease, disorder, or condition and/or the remission of the disease, disorder or condition.”
Therefore, the scope of claim 1 includes “prevention” of pain.
The term “GPR37L1 ligand”, while not explicitly defined, refers inherently to a compound that is an agonist to GPR37L1 receptor. A number of compounds determined via AI simulation to be GPR37L1 ligands are disclosed in Table 1, starting on p. 35 of the specification.
State of the Prior Art
The efficacy of MaR1 and NPD1 are discussed below (See 102 rejections). However, a search of the art did not result in any evidence that would suggest any of the other compounds listed in Table 1 are effective in treating or preventing pain.
Specifically, regarding claim 9, there was no art or patent literature at the time of the effective filing date that suggests the compound has any efficacy in treating pain.
Working Examples and Guidance
As stated above, the instant disclosure (Example 6, p. 35) teaches that a number of compounds were determined to be effective GPR37L1 ligands via AI simulation.
However, in the experiments disclosed in the instant specification, only MaR1, TX14, and NPD1 were tested for efficacy in binding to GPR37L1 (See p. 5, para. [0020]). Even amongst MaR1 and NPD1, there is a strong difference in efficacy. The specification states “Fig. 7D is a graph with the results of a B-arrestin 2 assay in hGPR37L1 expressed Chok1 cells showing the effects of MaR1, NPD1, and TX14. Of note, MaR1 is 10 times more potent that TX14, and NPD1 is a weaker agonist, compared to MaR1.” See below.
The structures of MaR1 and NPD1 are shown below.
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In contrast, compounds 3-18 have drastically different structures as exemplified by compounds 3-9 below.
While the ΔG values are similar, the fact that MaR1 is a full factor of 10 more effective than NPD1 indicates that ΔG does not predictably enable one of ordinary skill to apply any of the other compounds listed below.
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Further, there is nothing in the instant disclosure that would suggest the compounds above, MaR1, or NPD1 are effective in preventing pain.
Quantity of Experimentation
Considering the above, one of ordinary skill is already burdened with determining if compounds 3-18 display efficacy in binding to GPR37L1. In order for one of ordinary skill to determine if there is any efficacy as pain treatment, one of ordinary skill would require assays and in-animal testing as there is a significant level of unpredictability for compounds 3-18 as either treatment compounds and prevention compounds.
As claims 2-7 and 9-13 are dependent on claim 1, they are also rejected.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Indefiniteness – “Subject”
Claim 1 states “A method of treating pain in a subject, the method comprising administering a therapeutically effective amount of a GPR37L1 ligand to the subject.”
“Subject” is defined in para. [0043] of the specification. “Subject” is defined as “human and nonhuman animals.” The definition does not state whether the subject is in need of the method or not. Therefore, the claim is indefinite because it is not clear if the method is being administered to a subject in need of treatment or not.
As claims 2-13 are dependent on claim 1, they are also rejected.
Indefiniteness – Fragments, derivatives, esters, and variants
Claims 2 and 3 states “any fragments, derivatives, salts, esters, and variants thereof and any combinations thereof.”
These terms are indefinite because the claims and specification do not clearly state which fragments, derivatives, esters, or variants are being claimed. The specification does not define these terms and the lacks any disclosure that would allow one of ordinary skill in the art to determine the structure of “fragments, derivatives, esters, and variants”.
Art Rejections
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-5, 7-8 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Foster (US 2020/0121617) as evidenced by Doherty (Prostaglandins, Vol. 30, Iss. 5, 1985, 769-789).
Foster in para. [0182] - [0183] discusses administering maresin 1 to animals treated with zymosan to induce chronic pain. Foster states in para. [0182] states “During allodynia induction, the mice receive weekly injections of Zymosan (10 μg/ml in 10 μl saline) for a maximum of 6 injections, until a >33% reduction in pain threshold is observed for two consecutive weeks of testing”. Foster continues in para. [0183] stating “Using this approach, inventors confirmed that one could induce vulvar allodynia, measure pain responses via mechanical threshold determination, and assess treatment responses…Thus, inventors elected to test two commonly used, genetically tractable mouse strains: C57BL/6 background and test key compounds identified in Example 2 in C57BL/6 mice (.e.g., Maresin 1) as potential pain/inflammation resolving agents. Using the same experimental setup as pilot studies…it was found that weekly pain tests generated consistent reproducible values…for each C57BL/6 mouse. Collectively, inventors saw a progressive lowering of pain thresholds in mice receiving Zymosan…It was confirmed that allodynia persisted for a period of at least 5 weeks after allodynia induction…before initiating daily treatments with 1μg/mouse/day Maresin 1 for a period of 4 weeks. With treatment, inventors saw a complete restoration to the pre-induction thresholds, while PGE2 levels were suppressed and maintained at levels below baseline.”
Doherty in its title states “Intraperitoneal injection of zymosan in mice induces pain, inflammation and the synthesis of peptidoleukotrienes and prostaglandin E2. Therefore, the administration of Maresin1 to mice with pain induced by Zymosan disclosed in Foster embraces the instant claims.
Claim(s) 1-2, 4, 6-7 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Park (The Journal of Neuroscience, 2011, 31(42):15072-15085).
Park in its abstract states “Strikingly, NPD1 potently inhibits capsaicin-induced TRPV1 current…in dissociated dorsal root ganglion neurons, and this IC50 is = 500 times lower than that of AMG9810, a commonly used TRPV1 antagonist….Spinal injection of NPD1, at very low doses, blocks spinal [long term potentiation] and reduces TRPV1-dependent inflammatory pain, without affecting baseline pain.”
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.
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.
KSR Rationales
The MPEP in section 2143, subsection I gives examples of Rationales for supporting a conclusion of obvious. These rationales are non-exhaustive and include (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Claim(s) 1-8 and 10-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Foster (cited above) in view of Park (cited above), and as evidenced by Doherty (cited above).
In regards to claims 1-8, discussion of Foster, Park, and Doherty from the 102 rejections above are incorporated here.
Regarding claims 10-13, which are drawn to embodiments wherein the subject in need thereof is either undergoing treatment for cancer (claim 10), the subject is undergoing a chemotherapeutic regimen (claim 11), wherein the chemotherapeutic regiment comprises administration of paclitaxel or oxaliplatin (claim 12) or wherein the subject is being administered radiation therapy (claim 13), these limitations all specify the status of the subject who is experiencing pain. While the art does not specifically teach the administration of MaR1 or NPD1 to treat pain in a subject undergoing chemotherapeutic regimen comprising being administered radiation therapy, paclitaxel, or oxaliplatin, the common condition is that these patient types are experiencing pain in some capacity. As the art as indicated that both MaR1 and NPD1 are effective in treating pain, one of ordinary skill in the art would find it obvious to administer compounds known to treat pain to subjects experiencing pain, regardless of their status. The limitations of claims 10-13 do not sufficiently make clear how the status of the subject changes the type of pain they are experiencing such that administration of either MaR1 or NPD1 would be ineffective.
Therefore, one of ordinary skill in the art would find it prima facie obvious to administer either MaR1 or NPD1 to treat pain in a subject experiencing pain. One of ordinary skill would find motivation in that the art teaches MaR1 and NPD1 are effective for treating pain.
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.
Patent US 12,521,356
Claims 1-2, 4-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. US 12,521,356. Although the claims at issue are not identical, they are not patentably distinct from each other. The reference claims are drawn to a method of treating inflammatory pain or chronic pain comprising administering a therapeutically effective amount of NPD1.
Pertinent Art not Cited
Lopez (US20200163923) teaches Maresin compounds for use in treatment of central nervous system injuries.
Serhan (US20150119462) teaches 14-hydroxy-docosahexaenoic acid compound.
Ji (US20210228499, Patent Number 12,521,356, shares assignee and inventors) discloses method for treating pain, inflammation, malaria, and sepsis comprising administering a GPR37L1 ligand. Not cited as the publication date of this patent literature falls within the exception period.
Conclusion
No claims allowed.
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/LUISALBERTO GONZALEZ/Examiner, Art Unit 1624
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