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
This application, filed on 04 September 2024, is a National Stage entry from International Application No. PCT/CN2023/079387, filed on 02 March 2023 which claims priority under 35 U.S.C. 119 or 365 to Chinese Application Nos. CN202310020684 and CN202210210857, filed on 6 January 2023 and 4 March 2022, respectively. A certified copy of CN2023100206874 has been received, but a certified copy of CN202210210857 has not been received in its entirety. The copy of record consists of only 2 pages. Therefore, claim to priority under 35 U.S.C. 119 is improper.
Applicant is reminded of rule 37 C.F.R 1.55(f)(2):
Time for filing certified copy of foreign application—
(2) Application under 35 U.S.C. 371. A certified copy of the foreign application must be filed within the time limit set forth in the PCT and the Regulations under the PCT in an international application entering the national stage under 35 U.S.C. 371. If a certified copy of the foreign application is not filed during the international stage in an international application in which the national stage commenced on or after December 18, 2013, a certified copy of the foreign application must be filed within the later of four months from the date on which the national stage commenced under 35 U.S.C. 371(b) or (f) (§ 1.491(a) ), four months from the date of the initial submission under 35 U.S.C. 371 to enter the national stage, or sixteen months from the filing date of the prior foreign application, except as provided in paragraphs (h), (i), and (j) of this section.
Timely filing of the certified copy of CN202210210857 is required for a proper foreign priority claim.
Information Disclosure Statement
The information disclosure statements (IDSs) filed on 4 September 2024, 7 October 2025, and 5 February 2026 have been acknowledged and considered.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 9 and 10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
The claims do not fall within at least one of the four categories of patent eligible subject matter because claims 9 and 10 recite “use" of a product per se. "Use" claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101 "). In Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967). See MPEP 2173.05(q).
Claim Rejections - 35 USC § 112
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 9-10 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.
Claims 9-10 recite “use” of a product. Attempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986). See MPEP 2173.05(q). Accordingly, the instant “use” claims are indefinite because they recite a use of a product without setting forth any active steps defining how the use is practiced, leaving the metes and bounds of the claim unclear.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3 and 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019103952 (“Liu”) and WO2014074661 (“Moslin”) in view of Mäder et al., J. Med. Chem. 2020, 63, 14243−14275 (“Mäder”).
Liu teaches modulation of cytokines and/or interferons is crucial to protect against autoimmune disorders, like multiple sclerosis, and provide substantial therapeutic benefits to wide variety of patients (p. 5, lines 17-20 and 30-31; p. 6 lines 1-2). For example, Liu states: “Tyk2-deficient mice are resistant to experimental models of colitis, psoriasis and multiple sclerosis, demonstrating the importance of Tyk2-mediated signaling in autoimmunity and related disorders.” (p.5, lines 10-13).
Liu teaches compounds of Formula I,
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, which are useful as modulators of cytokines and/or interferons like, IL-12, -23 and/or IFNα, by inhibiting tyrosine kinase 2 (TYK2)-mediated signal transduction (p. 6, lines 5-7). R3, in the first, second, and third aspects of the invention, is defined as
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, wherein X is absent, O, or NH (pp. 9-11). Liu also teaches a pharmaceutical composition including a pharmaceutically acceptable carrier and at least one of the compounds disclosed (p. 6, lines 10-12). Example 159 is disclosed as having the following structure,
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(“Example 159”), and was prepared by reacting the intermediate,
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(“Intermediate”), with cyclopropyl amide in the presence of Xantphos, CsCO3, and Pd2dba3 in dioxane (p. 80).
Liu does not provide a specific species with a substituted or unsubstituted sulfoximine in place of the sulfone or a species with a phenyl core as opposed to a pyridine core, i.e., wherein L, from the instant claims, is
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and X is CH.
Moslin teaches modulation of cytokines and/or interferons is crucial to protect against autoimmune disorders, like multiple sclerosis, and provide substantial therapeutic benefits to wide variety of patients , for example humans with inactive variants of TYK2 are protected from multiple sclerosis and possibly other autoimmune disorders (¶¶[0010]-[0011]).
Moslin teaches compounds of formula I, which are useful as modulators of cytokines and/or interferons like, IL-12, -23 and/or IFNα, by inhibiting tyrosine kinase 2 (TYK2)-mediated signal transduction (¶[0012]), having the structure:
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(¶[0030]), wherein R2 is
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(¶[0033]), R3 is
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wherein R3aa is S(O)pRc, NRbSOpRc, etc., wherein Rb is C1-6 alkyl substituted and p is 0-2 (¶[0036]). Example No. 12 has the structure:
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, wherein R2 is the cyclopropyl carboxy group (vide supra), and R1 is CH3 (“Example 12”) (¶[00171]).
Moslin does not provide a specific species with a substituted or unsubstituted sulfoximine in place of the sulfone.
Mäder teaches sulfoximines are new and valuable isosteres of sulfur-containing functional groups, such as sulfones, for application in medicinal chemistry due to the ease of modulation of physicochemical properties. Mäder further teaches that sulfoximines are almost isosteric with sulfones and offer an additional vector capable of projecting a wide range of functionalities (p. 14244, 2nd column). For example, an optimization program identified sulfone 117 as a promising lead structure for inhibition of proline-rich tyrosine kinase 2 (PYK2), a non-receptor tyrosine kinase (pp.14262-63, Figure 20). Selectivity was an issue with 117 and it was further optimized to give the sulfoximine compounds 119 and 120, the free amino and N--alkylated derivatives, respectively. Improvement of IC50 of PYK2 was observed for both 119 and 120, but the N-alkylated derivative showed better cellular activity due to improved cell permeability. The (S)-120 stereoisomer showed further improvement in selectivity for PYK2 compared to (R)-120 and sulfone 117 (p.14263, 1st column).
Liu, Moslin, and Mäder are considered analogous art to the claimed invention because they are in the same field of optimizing non-receptor tyrosine kinase inhibitors for improved selectivity and potency. Therefore, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA), before the effective filing date of the claimed invention, to combine the teachings of the prior art elements to arrive at the compounds, compositions, and method instantly claimed with a reasonable expectation of success. The teachings of Liu and Moslin identified the need for further optimization of TYK2 inhibitors because they teach human individuals with inactive variants of TYK2 are protected from multiple sclerosis and other autoimmune disorders (vide supra); based on the teachings of Mäder, sulfoximines have emerged as valuable isosteres to sulfones and have significant potential to serve as a small, hydrophilic, and stable functional group in drug discovery as an isosteric alternative to sulfones (vide supra). It would have been prima facie obvious to substitute the sulfone functional group in Example 159 and Example 12, as taught by Liu and Moslin, respectively, with the sulfoximine functional group, because Liu provides motivation for the variability of the substituents bonded to the S atom in Example 159, namely X being absent, O, or NH, to improve potency and selectivity of inhibitors targeting TYK2. Moslin also teaches the same variability wherein R3aa could be a sulfoxide, sulfone, or a sulfoximine, wherein the N atom can be substituted with a C1-6 alkyl (vide supra). The teachings of Mäder provides further motivation for a PHOSITA to choose the sulfoximine functional group because based on the teachings, sulfoximine inhibitors of another non-receptor tyrosine kinase, PYK2, showed improved potency and selectivity, compared to its sulfone counterpart. Furthermore, the N--alkylated sulfoximine was preferred because it showed enhanced cell permeability compared to the free amino derivative (vide supra) (MPEP §2143(G)). Therefore, a PHOSITA would have had a reasonable expectation of success in arriving at compounds 2-4 of the instant claims through the combined teachings of Liu, Moslin, and Mäder. Accordingly, claims 1-3 and 6 are prima facie obvious.
Regarding claim 7, Liu teaches reacting the Intermediate, wherein R1 is CD3, A is NH, B is N, L is
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wherein X is O, and G is Cl, with cyclopropyl amide to arrive at Example 159 (vide supra). A PHOSITA would have had a reasonable expectation of success, based on the teachings of Liu, in reacting the sulfoximine derivative of the Intermediate, wherein X is NH, with cyclopropyl amide to arrive at compound 2 instantly claimed.
Regarding claim 8, Liu teaches a pharmaceutical composition including a pharmaceutically acceptable carrier and at least one of the compounds disclosed, like Example 159 (vide supra). It would have been prima facie obvious, based on the teachings of Liu, to have in a pharmaceutical composition, a compound wherein the sulfone of Example 159 is substituted with a sulfoximine, because Liu teaches a finite number of options of what the X atom bonded to the sulfur atom could potentially be including NH, and a pharmaceutically acceptable carrier.
Allowable Subject Matter
Claims 4-5 are 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.
Claims 4-5 specify the substituents of L wherein R3 is NH2 and R4 selected from the group consisting of halogen C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl and C3-C6 cycloalkyl-substituted C2-C6 alkynyl. The closest prior art is Liu which teaches the same pyridine core, i.e.,
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, with a variable substituent on the sulfur atom, wherein X is absent, O, or NH, and R6 is hydrogen, halo, C1-4 alkyl, C1-4 alkyoxy, C1-4haloalkyl, C1-4 haloalkoxy, C3-6 cycloalkyl, CN, NO2 or OH (p. 9, lines 15-21). The R6 substituents taught by Liu do not include NH2 nor does it include further substitution of the pyridine core. There is no teaching, suggestion, or motivation to further substitute the pyridine core with NH2 para to the sulfoximine functional group and ortho to the N atom of the pyridine core, or with substituents meta to both the N atom of the pyridine core and the sulfoximine functional group.
Conclusion
Claims 1-3 and 6-10 are rejected over the prior art.
Claims 4-5 contain allowable subject matter over the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHIL CHANDER AGGARWAL whose telephone number is (571)272-7755. The examiner can normally be reached 7am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAHIL CHANDER AGGARWAL/Examiner, Art Unit 1623
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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