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 Claims
Claims 1-20 are pending.
Priority
Instant application 18/574,511, filed 12/27/2023 claims priority as follows:
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Information Disclosure Statement
All references from IDS(s) received 12/27/2023, 08/09/2024, 03/12/2025, 04/23/2025, and 12/11/2025 have been considered unless marked with a strikethrough.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-15 in the reply filed on 03/23/2026 is acknowledged. Applicant’s election of the elected species compound 257, reading on claims 1-3, 5, 7, and 10-15 without traverse is also acknowledged.
Examination will begin with the elected species. In accordance with MPEP 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be examined again. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
The elected species was searched and applicable art was not identified. Therefore, the scope of the search was extended to the compounds recited in claim 14 and applicable art was not identified. The scope of the search was therefore extended to encompass a limited number of species reading on claims 1-3, 5, 7, and 10-15. Therefore, the entire scope of the claims has not yet been examined in accordance with Markush search practice. See MPEP 803.02.
Claims 4, 6, 8-9, and 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/23/2026.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the length exceeds 150 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 12 and 14 are objected to because of the following informalities:
Claim 12 appears to contain typographical errors. The variable definitions for Re “OH3” and “OF3” are being interpreted as “CH3” and “CF3”. Appropriate correction is required.
Claim 14 recites a table of compound structures. A substantial number of compound structures recited in claim 14 cannot be read clearly. See, for example, compound 066:
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Appropriate correction is required.
Claim Rejections – Improper Markush Group
Claims 1-3, 5, 7, 10-13, and 15 are rejected on the basis that it contains an improper Markush grouping of alternatives which contain species that fail to share a single structural similarity. 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 claims are drawn to compounds of formula (I) as follows:
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.
Separate dependent claims define BTKCL or E3CL separately. The definitions provided for BTKCL, such as:
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or
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or
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.
The Markush grouping of claims 1-3, 5, 7, 10-13, and 15 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:
FIRST, the alternatives are not members of the same recognized physical or chemical class or the same art-recognized class. For example, claim 1 embraces structurally unrelated compounds from among a virtually unlimited potential list of alternatives, the only requirement being that the compounds contain “a chemical ligand that can bind to BTK kinase” and “a chemical ligand that can bind to E3 ubiquitin ligase”.
Additionally, the alternatives are not disclosed in the specification or known in the art to be functionally equivalent and have a common use.
SECOND, the alternative chemical compounds – which do not belong to a recognized class and which are not disclosed in the Specification or known in the art to be functionally equivalent and have a common use as set forth above – do not share both a substantial structural feature and, thus, do not share a common use that flows from the substantial structural feature.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 12-13, and 15 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WANG (WO 2021219070 A1).
Wang discloses degraders of BTK comprising a BTK inhibitor moiety linked to a E3 ligase ligand moiety (Wang, abstract; [0009]). Wang discloses various compounds reading on the instant claims in the table of claim 30 (page 189, claim 30). For example, Wang discloses compound 22, compound 44, compound 58, compound 59, compound 65, compound 66, compound 67, compound 71, compound 72, compound 112, compound 113, compound 114, compound 123, compound 125, compound 126, compound 129, compound 130, compound 132, compound 137, compound 141, and compound 145 (pages 191-204). The aforementioned compounds comprise the same E3CL as the elected species:
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Many of the listed compounds also comprise the same linker L as the elected species:
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Accordingly, Wang discloses compounds which anticipate instant claims 1-3 and 12-13.
Claims 1-3, 12-13, and 15 are rejected under 35 U.S.C. 102(a)(1) and/or 102(a)(2) as being anticipated by ROBBINS (WO 2020081450 A1).
Robbins discloses degraders of BTK comprising a BTK inhibitor moiety linked to a E3 ligase ligand moiety (Robbins, abstract; [0007]). Robbins discloses various compounds reading on the instant claims in Table 1 (page 104, [0334]). As a (non-exhaustive) example, Robbins discloses compounds 102 and 103:
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The above compounds comprise an E3CL reading on the instant claims:
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The above compounds also comprise a linker L reading on the instant claims:
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Accordingly, Robbins discloses compounds which anticipate instant claims 1-3 and 12-13.
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.
Claims 5, 7, and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over ROBBINS (WO 2020081450 A1) applied to claims 1-3, 12-13, and 15 above, in view of ZHAOZHONG (WO 2015084998 A1).
The instant claims are drawn to compounds which are known as proteolysis targeting chimeras (PROTACs), a type of small-molecule drug that degrades disease-causing proteins rather than just inhibiting them. The compounds comprise a chemical ligand that can bind to BTK kinase linked to a chemical ligand that can bind to E3 ubiquitin ligase. The PROTAC achieves target protein degradation (in this case, BTK is the target protein for degradation) by inducing ubiquitination of target proteins.
PROTACs for degrading BTK are known in the prior art. The close prior art ROBBINS discloses degraders of BTK having Formula (A) and comprising a BTK inhibitor moiety linked to a E3 ligase ligand moiety (Robbins, abstract; [0007]-[0008]):
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Robbins discloses various compounds reading on the instant claims in Table 1 (page 104, [0334]). For example, Robbins discloses compounds 44, 71, 72, and 74 as compounds with excellent BTK degradation activity (Robbins, para. [0995]; Table 3) and oral bioavailability in a mouse model (Robbins, para. [1004]; Table 5):
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For claims 5, 7, and 11, the above compounds would otherwise read on the claim but are excluded by a proviso specifying that “when Y1 is selected from CH…R3 is not C1-C4 alkyl”.
For claim 10, the above compounds would otherwise read on the claim but are excluded by a proviso specifying that “when Y1 is selected from CH, R3 is selected from ring D”.
However, inhibitors of BTK having an imidazole ring substituted by groups other than C1-C4 alkyl are not new and were known in the prior art before the earliest priority date of the instant application. The close prior art ZHAOZHONG discloses inhibitors of BTK (Zhaozhong, abstract) having formula (IA) (para. [0007]), or in particular, Formula (Vc) (para. [00237]):
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where R4 is broadly defined (e.g. para. [00229]).
More specifically, Zhaozhong discloses chemical ligands of BTK having excellent inhibitory activity (<10 nM IC50) such as Compound 394, Compound 395, Compound 396, and Compound 402:
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(Example 277, [00793])
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(Example 278, [00796])
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(Example 279, [00797])
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(Example 280, [00798]).
The aforementioned compounds comprise a BTKCL moiety reading on the instant claims. The imidazolinone moieties in the above compounds are substituted by either a cyclopropyl or a substituted phenyl. Both of these moieties read on the claims, and are specifically recited in claim 10 for ring D.
Finding of prima facie obviousness
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (B) and/or (G), it would have been prima facie obvious to either (i) substitute the methyl group in the imidazolinone moiety of Robbins’ compounds for a cyclopropyl or chlorophenyl group taught by Zhaozhong; or (ii) substitute the entire BTK inhibitor moiety in Robbins’ compounds with a BTK inhibitor moiety taught by Zhaozhong. In either instance, a person having ordinary skill would have would have reasonably predicted that the substitution would result in a compound with utility as a BTK degrader. A person having ordinary skill would have been motivated to modify Robbins’ compounds in order to identify additional compounds having utility as BTK degraders.
Accordingly, claims 5, 7, and 10-11 are obvious over Robbins in view of Zhaozhong. Please also note that the compounds resulting from this substitution also read on claims 1-3, 12-13, and 15, which are already anticipated by Robbins as noted in the rejection under section 102 above.
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.
Claims 1-3 and 12-13, and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18/710,596 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application claims are drawn to structurally and functionally related compounds that read on the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-3, 5, 7, 10-13, and 15 are rejected. Claim 14 is objected to. Claims 4, 6, 8-9, and 16-20 are withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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