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 .
Status of the Claims
Claims 1, 65, 67, 68, 71, 76-78, 82, 85, 90, 91, 97, 98, 107, 108, 143, and 144 are pending.
Domestic Benefit
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Instant application is a U.S. National Stage Entry of PCT/US2022/047570, filed 10/24/2022. PCT/US2022/047570 claims benefit of U.S. Provisional Application No. 63/271,648, filed 10/25/2021. Therefore, the effective filing date is 10/25/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/04/2025 and 08/18/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Restriction Requirement/Election of Species
Applicant’s election without traverse of Group I, claims 1, 65, 67, 68, 71, 76-78, 82, 85, 90, 91, 97, 98, 107, 108, 143, and 144, drawn to compounds of Formula (II), in the reply filed on 08/18/2026 is acknowledged.
Applicant further elected the species K110, shown below, which reads on instant claims 1, 65, 67, 68, 71, 76-78, 82, 85, 90, 91, 97, 98, 107, 108, 143, and 144. The scope of the search will be limited to the elected species.
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Objections to the Specification – Abstract
The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
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. The abstract does not teach the genus of the compounds, only the use of the compounds as TYK2 degraders.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 reads “…-Cy- is independently at each occurrence is a bivalent ring selected from…sulfur, a 6-membered heteroarylenyl…” (emphasis added). This should instead read “…-Cy- is independently selected from… sulfur, and a 6-membered heteroarylenyl…” (emphasis added).
Appropriate correction is required.
Improper Markush Grouping
Claims 1, 67, 68, 71, 76-78, 85, 90, 97, 143, and 144 are rejected on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of Formula (II) is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the various permutations of variables TBM, L, A, L1, AAA results in compounds that only require a structure of an phenyl in common, which is not a significant structural similarity. The varying permutations are not recognized to belong to the same physical or chemical class or to be the same art-recognized class.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use. The scope of Formula (II) (inclusive of the elected species) that would form a proper Markush grouping would be where Q’ is defined, as in instant claim 65, or alternatively where A-L1-AAA is defined, as in instant claim 107. There would appear to be several different ways in which a proper Markush grouping could be derived from the scope instantly claimed. However, defining the Q’ or A-L1-AAA variables to constitute a common core structure would appear to be a minimum requirement, since the options for variables TBM, L, A, L1, AAA result in compounds with numerous dissimilar permutations.
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, 65, 67, 68, 71, 76-78, 82, 85, 90, 91, 97, 98, 107, 108, and 144 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 compound of Formula (II) where Ring 6A is pyrimidine optionally substituted with a halogen; R7 is -O(C1-3 alkyl), -SO2Me, or -OH, wherein there is only one occurrence of R7; R4 is C(O)NH-(C1-3 alkyl) or C(O)NH-cyclopropyl; Z7 is -NH-; Ring 5A is pyridine; and Cy is a 4-6-membered cycloalkyl, pyridine, or a 4-6-membered heterocycloalkyl ring containing 1 nitrogen atom, does not reasonably provide enablement for compounds of Formula (II). 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 the invention commensurate in scope with these claims.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention
The nature of the invention relates to compounds of Formula (II) in claim 1. Such compounds are useful as TYK2 degraders. This invention is also directed to compositions comprising said compounds.
Predictability of the art
The compounds synthesized in the instant specification appear novel. However, the hypothetical compounds in claim 1 would be unpredictable in terms of one skilled in the art being able to synthesize every possible compound claimed in instant claim 1. 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).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of skill in the art
An ordinary artisan in the area of drug development would have experience in synthesizing and screening chemical compounds for particular activities, such as a medical doctor or chemist. Screening 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 often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems.
4. The breadth of the claims
The scope of the claims involves compounds of Formula (II), shown below.
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Claim 1 is very broad in the number of variables and the options of substituents for each variable. There is an indefinite amount of hypothetical compounds included in claim 1.
5. The amount of direction provided, the presence or absence of working examples, and the quantity of experimentation necessary
The specification provides the synthesis of about 140 compounds. In all of the compounds synthesized, R4 is C(O)NH-(C1-3 alkyl) or C(O)NH-cyclopropyl; Z7 is -NH-; Ring 5A is pyridine; and Cy is a 4-6-membered cycloalkyl, pyridine, or a 4-6-membered heterocycloalkyl ring containing 1 nitrogen atom. Additionally, examples are only provided where Ring 6A is fluorine-substituted pyrimidine and R7 is -OMe or -OEt. However, it would be assumed that the inventors are also enabled for other Ring 6A being substituted by other halogens, and R7 being -OH or -OC3 alkyl, since these substituents are similar in size and reactivity.
Synthesis methods are not taught in the specification to provide for the aforementioned variables to include all of the possible substituents listed in the claims. It would be expected that the varying sizes or heteroatoms in the rings (e.g., Ring 5A, Ring 6A, Cy) and the varying sizes and reactivities of substituents (e.g., R7, R4) would change the reactivity of the compounds, and therefore would require alternate synthesis methods. It could also be possible that some combinations of compounds may not be able to be synthesized due to their instability. It would require one skilled in the art, such as a chemist, to perform thousands of reactions to determine which compounds of Formula (II) can be prepared and would likely require synthesis methods other than those provided in the specification. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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, 65, 67, 68, 71, 76-78, 82, 85, 90, 91, 97, 98, 107, 108, and 144 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.
Claim 1 recites the variable (R2)m in Formula (II). The claims provide no definition for R2 or m, rendering the claim and its dependent claims 65, 67, 68, 71, 76-78, 82, 85, 90, 91, 97, 98, and 144, where “A” is not defined, indefinite.
Claim 1 recited that “Ring A-L1-Ring AAA is selected from…”. There is insufficient antecedent basis for this limitation in the claim. There is no variable labeled “Ring A” or “Ring AAA” in Formula (II) or (IIIA). This renders the claims and its dependent claims 65, 67, 68, 71, 76-78, 82, 85, 90, 91, 97, 98, 107, 108, and 144, where the compound is not structurally defined, indefinite.
Claim 107 recites the limitation "wherein the E3 ubiquitin ligase binding moiety is…". There is insufficient antecedent basis for “the E3 ubiquitin ligase binding moiety” in the claim.
Claim 1 recites the limitation “Ring 6A is phenyl and a 5-6 membered heteroaryl”. This renders the claim and its dependent claim 65, 67, 68, 76-78, 85, 91, 97, 107, and 144, where Ring 6A is not structurally defined, indefinite, since Ring 6A cannot be both a phenyl and a 5-6 membered heteroaryl.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 143 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 143, which depends from claim 1, contains compounds which do not contain the phenyl moiety required by claim 1 in Formula (IIIA) (e.g., K122-125 and K127). Therefore, claim 143 fails to include the subject matter of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
Claims 1, 65, 67, 68, 71, 76-78, 82, 85, 90, 91, 97, 98, 107, 108, 143, and 144 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RILLA M SAMSELL whose telephone number is (703)756-5841. The examiner can normally be reached Monday-Friday, 7-3.
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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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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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