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 Claims
Claims 1-4 and 6-25 are pending in the instant application.
Claim 5 has been canceled.
Withdrawn Objections/Rejections
Applicant has canceled Claim 5, rendering the rejection thereof on the grounds of nonstatutory double patenting moot. This rejection is hereby withdrawn.
Information Disclosure Statement
The Information Disclosure Statement filed March 5th, 2026 has been fully considered by the examiner, except where marked with a strikethrough.
Specification
Applicant failed to address the objection to the abstract raised in the non-final office action mailed September 5th, 2025.
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.
Presently, the abstract refers to a crystalline form II represented by formula 1, but the absence of a structural formula or description of the class of compound of crystalline form II is missing from the abstract. This objection is maintained.
Claim Rejections - 35 USC § 112
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.
The rejection of Claims 1-4 and 6-13 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph is maintained and extended to newly presented Claims 14-24, because the specification, while being enabling for a crystalline form II of a compound of Formula 4, as now recited at instant Claim 25, does not reasonably provide enablement for a crystalline form II of any compound of formula 1. 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 and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Applicant has traversed this rejection in view of the amended limitation of instant Claim 1 requiring 5 or more characteristic XRPD peaks to distinguish crystalline form II.
The examiner does not find this persuasive. As noted in the non-final rejection mailed September 5th, 2025, enablement is lacking because “crystalline form II” refers to the hydrate prepared via the method disclosed at Page 30, Paragraphs [00145-00147] with a powder XRD diffraction pattern characterized by the values listed at Page 31, Paragraph [00154] and also disclosed at Table 1 on Page 32 of the instant specification.
In other words, “crystalline form II” as instantly recited at Claim 1 is defined specifically by the instant specification as the crystalline form of the structure disclosed at Paragraph [00146] of the instant specification. A specific crystal form, once defined, cannot refer to distinct crystal forms of multiple distinct compounds. While the instant limitation recites the X-ray powder diffraction pattern has 5 or more characteristic peaks selected from those listed in the claim, “crystalline form II”, as defined, necessarily will produce an XRPD diffraction pattern as disclosed at Paragraph [00154] of the instant specification, which corresponds to the structure disclosed at Paragraph [00146]. While crystalline forms of other compounds of formula 1 are certainly possible, these polymorphs cannot, by definition, be crystalline form II.
For clarity of the record, the Wands factors discussed in the non-final rejection mailed September 5th,2025 are revisited below.
Nature of the invention:
The invention is drawn to a crystalline form II of a compound having the formula 1:
PNG
media_image1.png
224
253
media_image1.png
Greyscale
Wherein R1 is C2-C5 alkyl.
Breadth of the invention:
The scope of the claimed invention is narrow, as it is drawn to a single polymorph defined by a specific X-ray powder diffraction pattern.
State of the prior art and predictability in the art:
With respect to powder X-ray diffraction patterns, Thakral et. al. (“Applications of Powder X-Ray Diffraction in Small Molecule Pharmaceuticals: Achievements and Aspirations”, Journal of Pharmaceutical Sciences, 107, 2969-2982, 2018; cited in non-final rejection mailed September 5th, 2025; hereinafter referred to as Thakral) represents the state of the prior art.
At Page 2973, the first paragraph under “Identification and Quantification of API”, Thakral teaches “The X-ray powder pattern of every crystalline form of a compound is unique and can be used for identification.”
The instant claims are drawn to a single crystalline form II of a compound of formula 1, representative of a multitude of compounds due to the variability of R1, and multiple pharmaceutically acceptable salts and/or solvates thereof. It is counter to what is known in the art as taught by Thakral for a single crystalline form II of a compound to characterize a multitude of polymorphs by a single X-ray powder diffraction pattern.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
At Page 29, Paragraphs [00140]-[00143] of the instant specification, a procedure for the preparation of an amorphous hydrochloride salt of a compound of formula 1, specifically N-((3S,5S)-1-((3S,4R)-1-(tert-butyl)-4-(4-chlorophenyl)pyrrolidine-3-carboly)-5-morpholine-4-carbonyl)pyroolidine-3-yl)-N-((1S,4R)-4-methylcyclohexyl)isobutyramide hydrochloride is sufficiently disclosed.
At Page 30, Paragraphs [00145-00147], a procedure for the preparation of crystalline form II of a hydrate of this compound is sufficiently disclosed.
At Pages 31-32, Paragraphs [00151]-[00155] of the instant specification, the method for obtaining a powder XRD diffraction pattern and the results thereof are sufficiently disclosed.
To this end, “crystalline form II” refers to the hydrate prepared via the method disclosed at Page 30, Paragraphs [00145]-[00147] with a powder XRD diffraction pattern characterized by the values listed at Page 31, Paragraph [00154] (also disclosed at Table 1 on Page 32 of the instant specification).
Therefore, the specification is sufficiently enabled for a crystalline form II, as noted above, characterized by the hydrate prepared via the method disclosed at Page 30, Paragraphs [00145]-[00147] with a powder XRD diffraction pattern characterized by the values listed at Page 31, Paragraph [00154], but is not enabled for a crystalline form II of a compound, wherein the crystalline compound is of formula 1, pharmaceutically acceptable salts or solvates thereof other than the disclosed hydrate described above.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p).
MPEP § 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F. 2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for making these compounds.
The rejection of Claims 12-13 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is maintained. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Applicant has traversed this rejection in the remarks filed March 5th, 2026, stating simply at the third paragraph of page 7 of the remarks that, “Applicant respectfully disagrees.”
The examiner does not find this argument persuasive.
For clarity of the record, the Wands factors addressed in the non-final rejection mailed September 5th, 2025 are revisited below.
Nature of the invention:
The invention is drawn to a method for agonizing the function of a melanocortin-4 receptor and for treating obesity, diabetes, inflammation, or erectile dysfunction.
Breadth of the claimed invention:
The scope of the claimed invention is limited, as it is drawn to agonism of melanocortin-4 receptor and treatment of a finite list of conditions including obesity, diabetes, inflammation, or erectile dysfunction.
State of the prior art and predictability in the art:
With respect to agonism of melanocortin-4 receptor, Kang et. al. (US 2022/0289731 A1; cited on Applicant’s Information Disclosure Statement filed February 20th, 2024; cited in non-final office action mailed September 5th, 2025; hereinafter referred to as Kang) represents the state of the prior at.
At Page 9, Kang teaches the following hydrochloride salt as Example 1:
PNG
media_image2.png
208
250
media_image2.png
Greyscale
This is a compound of Formula 1, as recited at instant Claim 1, and is the anhydrate of the compound of Formula 4, as recited in instant Claim 5.
At Pages 14-15, Tables 1-4, Kang sufficiently discloses data demonstrating Example 1 as an agonist of the melanocortin-4 receptor. At Page 17, Paragraph [0175], Kang teaches administration of Example 1 resulted in significant weight loss in a mouse obesity model. No data, however, has been provided demonstrating Example 1’s efficacy in treating diabetes, inflammation, or erectile dysfunction.
The instant application is drawn to administration of crystalline form II, a polymorph of Example 1. With respect to predictability of polymorphs of active pharmaceutical ingredients (APIs), Thakral represents the state of the prior art.
At Page 2969, Second Paragraph, Thakral teaches “Polymorphs can show a wide range of physical and chemical properties, including different melting points and spectral properties. Polymorphs can also exhibit different solubility, density, hardness and crystal shape. Control of polymorphism is specifically important in cases where changing the polymorph can affect bulk properties, dissolution rate, bioavailability, hygroscopicity, and chemical or physical stability of a drug.”
Therefore, in view of Thakral, the pharmaceutical properties of the amorphous salt of Example 1, taught by Kang, as noted above, does not predictably correspond to the polymorph of crystalline form II demonstrating the same pharmaceutical properties.
The amount of direction provided and working examples:
No examples have been provided in the instant specification to provide enabling disclosure of administration of the crystalline form II for agonizing the function of a melanocortin-4 receptor or for the treatment of obesity, diabetes, inflammation or erectile dysfunction.
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. A person having ordinary skill in the art would need to identify and/or develop methods to evaluate the efficacy of a crystalline form II in agonizing the function of melanocortin-4 receptor and/or treating obesity, diabetes, inflammation, or erectile dysfunction, with no assurance of success.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
Genentech Inc. v Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore in view of the Wands factors and in re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person having ordinary skill in the art would have to engage in undue experimentation to determine the efficacy of administration of a crystalline form II in agonizing the function of melanocortin-4 receptor and/or treating obesity, diabetes, inflammation, or erectile dysfunction, with no assurance of success.
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.
The provisional rejection of Claim 6 on the ground of nonstatutory double patenting as being unpatentable over claim 5 of copending Application No. 18/258,711 (reference application) is maintained.
Applicant has traversed this rejection stating at the second paragraph of page 8 of the remarks filed March 5th, 2026, “Applicant disagrees and respectfully requests that the nonstatutory double patenting rejections be held in abeyance until there is a favorable indication of allowable subject matter.” This is not persuasive to overcome the rejection. For clarity of the record, the rejection as raised in the non-final rejection mailed September 5th, 2025 is revisited below.
Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to a method of preparing a crystalline form a compound of Formula 1, wherein Formula 1 is
PNG
media_image3.png
230
237
media_image3.png
Greyscale
. Although nominally, the claims are drawn to methods of preparing distinct crystalline forms of a compound of Formula 1, the methods of preparation are identical, as both Claim 6 in the instant application and Claim 5 in the reference application are drawn to preparing a mixed solution by dissolving a compound of Formula 1 in a crystallization solvent and obtaining crystals from the mixed solution. Per MPEP 2112.01, I., “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977).”
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The provisional rejection of Claim 6 on the ground of nonstatutory double patenting as being unpatentable over claim 6 of copending Application No. 18/258,730 (reference application) is maintained.
Applicant has traversed this rejection stating at the second paragraph of page 8 of the remarks filed March 5th, 2026, “Applicant disagrees and respectfully requests that the nonstatutory double patenting rejections be held in abeyance until there is a favorable indication of allowable subject matter.” This is not persuasive to overcome the rejection. For clarity of the record, the rejection as raised in the non-final rejection mailed September 5th, 2025 is revisited below.
Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to a method of preparing a compound of Formula 1, wherein Formula 1 is
PNG
media_image4.png
240
229
media_image4.png
Greyscale
. Although nominally, the claims are drawn to methods of preparing distinct crystalline forms of a compound of Formula 1, the methods of preparation are identical, as both Claim 6 of the instant application and Claim 6 in the reference application are drawn to preparing a mixed solution by dissolving a compound of Formula 1 in a crystallization solvent and obtaining crystals from the mixed solution. Per MPEP 2112.01, I., “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977).”
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The provisional rejection of Claims 1-4 and 6-13 on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 11-16 of copending Application No. 18/258,717 (reference application) is maintained and extended to newly presented claims 14-25.
Applicant has traversed this rejection stating at the second paragraph of page 8 of the remarks filed March 5th, 2026, “Applicant disagrees and respectfully requests that the nonstatutory double patenting rejections be held in abeyance until there is a favorable indication of allowable subject matter.” This is not persuasive to overcome the rejection. For clarity of the record, the rejection as raised in the non-final rejection mailed September 5th, 2025 is revisited below.
Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to a crystalline Form II of a compound of Formula 1, wherein Formula 1 is
PNG
media_image4.png
240
229
media_image4.png
Greyscale
, pharmaceutical compositions thereof, and a method of agonizing melanocortin-4 receptor and for treating obesity, diabetes, inflammation, or erectile dysfunction comprising administration of these pharmaceutical compositions. Although the XRPD characteristic peaks recited in each application’s respective Claim 1 are not identical, at least 5 characteristic peaks are within the margin of error (±0.2o 2[Symbol font/0x71]) of the recited peaks. For example, the instantly recited peaks in Claim 1 of 7.77±0.2o, 9.82±0.2o, 11.37±0.2o, 12.36±0.2o, and 15.17±0.2o overlap with the peaks recited in the reference application’s Claim 1 of 7.5964±0.2o, 9.978±0.2o, 11.400±0.2o, 12.427±0.2o, and 15.122±0.2o. Therefore, these claims are not patentably distinct, as they are both drawn to a crystalline form of a compound of Formula 1 with at least 5 overlapping characteristic peaks observed in the XRPD pattern.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-4 and 6-25 are rejected.
No claim is 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/D.J.B./ Examiner, Art Unit 1624
/JEFFREY H MURRAY/ Supervisory Patent Examiner, Art Unit 1624
Prosecution Insights