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 .
Priority
Examiner acknowledges that, according to the Filing receipt received 04/08/2024, that the instant application 18/558,812 filed 11/03/2023 is a 371 of PCT/KR2022/006482 filed 05/06/2022 which claims foreign priority of Republic of Korea application 10-2021-0059376 filed 05/07/2021.
Information Disclosure Statement
The Information Disclosure Statement filed on 11/03/2023 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of list of references cited from the IDS is included with this Office Action.
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.
Claim 9 is 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.
Claim 9 is directed toward a composition comprising the co-crystal of claim 1 and a pharmaceutically acceptable carrier. However, the scope of the composition includes compositions wherein the co-crystal would be dissolved in a liquid solution (see paragraph [88] of the specification, which includes solubilizing agents and solubilizers). The crystal structure of the co-crystal would not be maintained if in solution. As such it is unclear how the co-crystal of claim 1 would be maintained in a composition comprising a solubilizing agent or otherwise in a liquid solution.
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.
Claims 1-2 and 4-11 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 a co-crystal of formula 1 and vanillin, wherein the compound of formula 1 is N-((3S,5S)-1-((3S,4R)-1-(tert-butyl)-4-(4-chlorophenyl)pyrrolidine-3-carbonyl)-5- (morpholine-4-carbonyl)pyrrolidin-3-yl)-N-((1s,4R)-4-methylcyclohexyl)isobutyramide, does not reasonably provide enablement for a co-crystal of formula 1 (generally) and vanillin. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The claims are drawn to a co-crystal of a compound of formula 1 and vanillin with at least 5 claimed XRPD peaks. Formula 1 is set forth in claim 1 as below.
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Formula 1 is not directed toward a single compound species but rather a genus wherein R1 is C2-C5 alkyl. The working examples in the specification only demonstrate co-crystallization of one species of formula 1 with vanillin, which has the structure as below, wherein the co-crystal exhibits the requisite number of claimed XRPD peaks.
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The working examples fail to demonstrate a co-crystal of a compound of formula 1 with vanillin for any other compounds within the scope of formula 1, let alone with at least 5 of the XRPD peaks of claim 1. The preparation of crystalline forms and co-crystals is generally considered unpredictable in the art despite a high level of skill. MPEP 2164.03, “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).” One of ordinary skill in the art would not be able to ascertain whether another compound of formula 1 would be (i) able to co-crystallize with vanillin; and (ii) form a co-crystal with vanillin that exhibits at least 5 of the claimed XRPD peaks. Given the lack of guidance and in view of the level of unpredictability in the art, one of ordinary skill in the art would not be able to make the co-crystal of claim 1 with any other compound of formula 1 except for N-((3S,5S)-1-((3S,4R)-1-(tert-butyl)-4-(4-chlorophenyl)pyrrolidine-3-carbonyl)-5- (morpholine-4-carbonyl)pyrrolidin-3-yl)-N-((1s,4R)-4-methylcyclohexyl)isobutyramide, shown above, without undue experimentation.
Claims 5-8 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 a method of preparing the co-crystal of claim 1 (within the scope of the above enablement rejection) wherein the method comprises the steps of preparing a mixed solution in which the formula 1 and vanillin are mixed as in paragraph [67] or [68] and obtaining the co-crystal of the compound of formula 1 and vanillin as in paragraphs [73]-[74] of the instant specification, does not reasonably provide enablement for preparing a mixed solution of formula 1 and vanillin generally and obtaining the co-crystal from the mixed solution generally. 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.
Claims 5-8 are directed toward methods of preparing the co-crystal of claim 1. The claims encompass an incredibly broad scope comprising preparing a mixed solution of formula 1 and vanillin generally and obtaining the co-crystal from the mixed solution generally. Dependent claims 6-8 narrow portions of the scope of claim 5 but are largely limited to narrowing the molar ratio or the solvent, which is still broader in scope than the working examples. The working examples of the specification fall within the scope of paragraphs [67]-[68] and [73]-[74] which comprise three different steps of adding solvents and obtaining the co-crystal by stirring and evaporating. One would not be able to predict whether, if any other solvent or experimental conditions were used, the claimed co-crystal would form. The preparation of crystalline forms and co-crystals is generally considered unpredictable in the art despite a high level of skill. MPEP 2164.03, “The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).” Given the lack of guidance and in view of the level of unpredictability in the art, one of ordinary skill in the art would not be able to make the co-crystal of claim 1 via the methods of claims 5-8 without undue experimentation.
Claim 11 is 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 obesity, diabetes, inflammation, or erectile dysfunction, does not reasonably provide enablement for preventing obesity, diabetes, inflammation, or erectile dysfunction. 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.
As stated in the MPEP 2164.01 (a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.”
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
It is presumed “prevention” of the claimed disease would require a method of identifying those individuals who will develop the claimed diseases before they exhibit symptoms. There is no evidence of record that would guide the skilled clinician to identify those who have the potential of becoming afflicted.
The factors to be considered in making an enablement rejection were summarized above. 1) As discussed above, preventing diseases requires identifying those patients who will acquire the disease before the obesity, diabetes, etc. occurs. This would require extensive and potentially opened ended clinical research on healthy subjects. 2) The scope of the claims encompasses both treatment and prevention. 3) There is no working example of such a preventive procedure in man or animal in the specification. 4) The claims rejected are drawn to clinical pharmacology and are therefore physiological in nature. 5) The state of the art is that no general procedure is art-recognized for determining which patients generally will suffer from the claimed conditions before the fact. 6) The artisan using Applicants invention would be a Board-Certified physician with an MD degree. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting a compound to be effective for the prevention of the claimed conditions. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable to any agent to be able to prevent obesity, diabetes, etc. That is, the skill is so low that no compound effective generally against the prevention of obesity, diabetes, etc. 7) It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved" and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed diseases.
Allowable Subject Matter
Claim 3 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The closest prior art is intervening reference WO 2021/091283 (IDS filed 11/03/2023), which discloses compounds of Formula 1. However, WO 2021/091283 does not teach or suggest any crystalline forms of the compounds of Formula 1, nor is there any teaching or suggestion to co-crystallize the compounds with vanillin. One of ordinary skill in the art would not be motivated to co-crystallize the compounds with vanillin, let alone have a reasonable expectation of forming the claimed co-crystal and requisite XRPD peaks.
Conclusion
No claims are allowed. Claim 3 is objected to. Claims 1-2 and 4-11 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADELINE E BRAUN whose telephone number is (703)756-4533. The examiner can normally be reached M-F 8:30am-5:00pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/M.E.B./Examiner, Art Unit 1624 04/29/2026
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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