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 .
Claim Status
Claims 1, 11-14, and 16-19 are currently pending and under examination.
Claims 2-10 are canceled.
Claims 16-19 are allowable.
Claims 1, 11 -14 are rejected.
Any rejection found in the previous Office Action and not presented herein has been withdrawn based upon Applicant’s amendments.
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.
Claims 1, and 11-14 remain 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 cocrystal comprising (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8- yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1) and a coformer, wherein the coformer and specific ratio of upadacitinib:coformer is 4-acetamidobenzoic acid at a ratio of 1:1, 4-hydroxybenzoic acid at a ratio of 1:1.5, 4-hydroxy-3-nitrobenzoic acid at a ratio of 1:2, 3,4-dihydroxybenzoic acid at a ratio of 1:1, or gallic acid at a ratio of 1:1, does not reasonably provide enablement for an upadacitinib:coformer ratio of outside of the specific values used in examples, as listed above. (Of note: Applicant is only enabled for the specific ratios of upadacitinib:coformer with the specific coformers set forth above, as exemplified in the specification. As instantly written, all five coformers in claim 1 are claimed to form a cocrystal with Upadacitinib at any ratio between 1:1.5 and 1.5:1. Each coformer is demonstrated to form a cocrystal with Upadacitinib at a specific ratio.)
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. Shukla, R. (The origin of synthons and supramolecular motifs: beyond atoms and functional groups), IUCrJ, Vol. 12, pp. 334-357 (Year: 2025) explains that knowledge of hydrogen bonding alone cannot predict the formation of a cocrystal, and only experimental verification can verify successful cocrystal formation. (See page 12-13; Introduction).
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: 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 regard to the instant claims, with the most relevant factors discussed below.
Nature of the Invention: Claim 1 is drawn to
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However, Applicant only demonstrates cocrystal formation between upadacitinib and each of the five exemplified coformers, at ratios that are specific to the coformer used. Cocrystal formation is highly unpredictable, and demonstration of success using these select species at their specific exemplified ratios, does not enable one skilled in the art to create the instantly claimed cocrystals using any ratio between 1:1.5 and 1.5:1.
Breadth of the Claims: The claims are broad in that the claims recite a cocrystal comprising (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8- yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1) and a coformer, selected from
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wherein a molar ratio of compound 1 (Upadacitinib) to coformer is from about 1:1.5 to about 1.5:1. The claims recite a range of upadacitinib:coformer ratios outside of what the Applicant has shown by working example. Cocrystal formation is highly unpredictable, as are the specific ratios at which they form. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the Specification and Existence of Working Examples: The specification describes utilizing a select few species of compounds (4-acetamidobenzoic acid, 4-hydroxybenzoic acid, 4-hydroxy-3-nitrobenzoic acid, 3,4-dihydroxybenzoic acid, and gallic acid) in formation of cocrystals with Upadacitinib, (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8- yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide. The specification also shows specific ratios of upadacitinib:coformer at which these coformers form cocrystals with Upadacitinib.
However, the specific ratios of upadacitinib:coformer exemplfied, does not enable one skilled in the art to practice the claimed invention to the extent that the ratio of Upadacitinib:coformer, are broader than exemplified.
While it is noted that the applicant has shown data for cocrystal formation in select species, at specific ratios of upadacitinib:coformer, the applicant is not enabled for the full-scope of cocrystals comprising (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8- yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1) and a coformer, selected from
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wherein a molar ratio of compound 1 (Upadacitinib) to coformer is from about 1:1.5 to about 1.5:1.
Predictability and State of the Art: The state of the art at the time the invention was made was unpredictable and underdeveloped. It is known in the art that the development of cocrystals is highly dependent on the unique molecular properties between the coformer and the pharmaceutical compound. In addition, not all species of coformers are effective in forming cocrystals with all pharmaceutical compounds. While the formation of select cocrystals are exemplified by the applicant, due to the unpredictable nature of cocrystal formation the applicant does not disclose the full-scope of cocrystals comprising (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8- yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1) and a coformer, wherein the ratio of compound 1 (Upadacitinib): coformer is from about 1:1.5 to about 1.5:1.
As previously mentioned, Shukla, R. (The origin of synthons and supramolecular motifs: beyond atoms and functional groups), IUCrJ, Vol. 12, pp. 334-357 (Year: 2025) explains that knowledge of hydrogen bonding alone cannot predict the formation of a cocrystal, and only experimental verification can verify successful cocrystal formation. (See page 12-13; Introduction).
Amount of Experimentation Necessary: The quantity of experimentation necessary to carry out the claimed invention is high, as the skilled artisan could not rely on the prior art or instant specification to teach the full-scope of cocrystals comprising (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8- yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide (Compound 1) and a coformer, selected from
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wherein a molar ratio of compound 1 (Upadacitinib) to coformer is from about 1:1.5 to about 1.5:1.
In order to carry out the claimed invention, one of ordinary skill in the art would have to conduct XRPD experiments similar to the Applicant’s, with each and every cocrystal formed between Upadacitinib and the five exemplified coformers, wherein a molar ratio of compound 1 (Upadacitinib) to coformer is from about 1:1.5 to about 1.5:1.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 1, and 11-14 are not considered to be fully enabled by the instant specification.
Response to Arguments
Examiner’s objection to Applicant’s drawings for duplicates of figures 1-3, 4-5, 6-7, and 8-9 has been rendered moot following the Applicant’s amendments to the specification providing further detail elucidating the differences between the figures.
Applicant’s arguments filed 2/13/2026 have been fully considered, but are not persuasive.
In regards to the traversal of the 35 U.S.C. 112 rejection of claims 1-3, and 9-15:
Applicant has canceled claims 2, 3, 9, and 15 in this rejection. Claims 1, and 11-14 remain rejected for the following reasons:
Applicant submits that the range of molar ratios recited in claim 1 as amended and claims 11-14 depending therefrom, are commensurate in scope with the exemplified cocrystals of the Application.
This is not found persuasive because the Applicant’s claim 1 as amended, continues to include ratios of Upadacitinib:coformer that are not exemplified by the Applicant. The Applicant’s claim 1 as written, includes all five of the coformers (4-acetamidobenzoic acid, 4-hydroxybenzoic acid, 4-hydroxy-3-nitrobenzoic acid, 3,4-dihydroxybenzoic acid, and gallic acid) at any ratio of Upadacitinib:coformer between about 1:1.5 to about 1.5:1.
This is broader subject matter than what the Applicant has demonstrated to form cocrystals. Applicant particularly exemplifies cocrystal formation between Upadacitinib and 4-acetamidobenzoic acid at a specific ratio of 1:1, Upadacitinib and 4-hydroxybenzoic acid at a specific ratio of 1:1.5, Upadacitinib and 4-hydroxy-3-nitrobenzoic acid at a specific ratio of 1:2, Upadacitinib and 3,4-dihydroxybenzoic acid at a specific ratio of 1:1, and Upadacitinib and gallic acid at a specific ratio of 1:1.
Therefore, the rejection is maintained for the reasons of record and the reasons set forth above.
Conclusion
Claims 16-19 are allowed.
Claims 1, and 11-14 are rejected.
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 OROD MOTEVALLI whose telephone number is (571)272-6026. The examiner can normally be reached Monday - Friday 10:00AM - 6:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OROD MOTEVALLI/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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