DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election of Group I, and species of compound 1 (claims 1, 2 and 4-9), in the reply filed on June 4, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
3. Examination followed guidelines provided by MPEP 803.02. The elected species appeared to be obvious over the prior art. Furthermore, a nonelected species was found to be anticipated by the prior art. Therefore, the Markush claims were rejected and claims to nonelected species were withdrawn from further consideration. The claims were searched to the extent of the elected species and the nonelected species shown below.
4. Claims 11-13 and 17-27 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter. Election was made without traverse in the reply filed on April 8, 2025.
Information Disclosure Statement
5. The information disclosure statements (dated January 4, 2023 and October 3, 2022 and June 30, 2021) were in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The IDS was considered. Signed copies of form 1449 are enclosed herewith.
Status of Claims
6. Claims 1, 2, 4-9, 11-13 and 17-27 are pending. Claims 1, 2 and 4-9 are elected of which claim 1 is independent. Claims 11-13 and 17-27 are nonelected.
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.
7. Claim(s) 1, 2 and 9 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2018148440. The reference has a publication date of August 16, 2018 which antedates the present claims having an effective filing date of January 6, 2020 and priority claim to provisional application dated January 7, 2019. The reference teaches heterobifunctional compounds of structure degron-linker-dTAG targeting ligand (page 127). The heterobifunctional compounds bind to ubiquitin ligase and targeting ligand representing a moiety selectively bind to, for example, FKB1236V. Eg. see page 5 and page 15, and entire document. The reference teaches specific embodiments such as
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(page 379). The embodiment corresponds to the present claims in the following manner: TL is
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; linker-degron is
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. The reference teaches pharmaceutical compositions of the heterobifunctional ligand and the specific embodiment above (eg. 63 page 378).
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.
8. Claims 1, 2 and 4-9 is/are rejected under 35 U.S.C. 103 as being obvious over WO2018148440 in view of WO 2017024318 (published February 9, 2017) and further in view of US 20170327469 (published November 16, 2017).
Determining the scope and contents of the prior art
WO 2018148440 teaches heterobifunctional compounds that bind to ubiquitin ligase and targeting ligand representing a moiety selectively binding to, for example, FKB1236V. The heterobifunctional compound has structure degron-linker-dTAG targeting ligand (page 127) – present claim 1. The reference teaches specific embodiments to the targeting ligands, for example, the preferred embodiment of
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- present claim 2. The reference teaches pharmaceutical compositions of the heterobifunctional ligand and the specific embodiment above (eg. 63 page 378) – present claim 9.
WO2017024318 teaches heterobifunctional compounds that bind to ubiquitin ligase and targeting ligand representing a moiety selectively binding to, for example, FKB1236V (eg. pages 6, 37, 90, entire document). The heterobifunctional compound has structure degron-linker-dTAG targeting ligand (page 92):
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or embodiments such as
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and more specifically
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(page 258) wherein linker-Y that binds to degron and dTAG has structure of
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and wherein the linker is
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and Y is NH. The linker corresponds to the present claims in the following manner: o=n=1; X is C6 alkyl, m=0 or linker on page 4, 5th embodiment.
US 20170327469 teaches bifunctional compounds for degrading proteins (abstract) by binding to E3 ubiquitin ligase and have structure
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wherein ULM is ubiquitin binding moiety and L is a linker. ULM corresponds to degron which binds to ubiquitin ligase of the present claims. The reference provides preferred embodiments for ULM such as
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(page 15) which corresponds to D1 of the present claims.
Ascertaining the differences between the prior art and the claims at issue
WO 2018148440 does not teach the specific structures of the L10 of claim 4, the linker of claim 5, the dTAG-linker of claim 6, the degron of claim 7, and the species of claim 8 including the elected species of compound 1.
Resolving the level of ordinary skill in the pertinent art and considering objective evidence present in the application indicating obviousness
MPEP 2143 B provides basic requirements of prima facie case of obviousness including examples of rationale of the simple substitution of one known element for another to obtain predictable results. To reject a claim based on this rationale the following is considered below and applied to the present claims:
A finding that the prior art method differs from claimed method by the substitution of some component with another component
WO 2018148440 does not teach the specific structures of claims 4, 5, 6, 7 and 8 including Applicant’s elected species. The prior art differs from the claims by substitution of degron and linker into the structure of dTAG-linker-degron in a heterobifunctional compound that bind to ubiquitin ligase and FKBP12F36V.
A finding that the substituted components and their functions were known in the art
WO2017024318 teaches heterobifunctional compounds that bind to ubiquitin ligase and targeting ligand representing a moiety selectively binding to FKB1236V wherein the linker structure of
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(present claims 4 and 5) is taught. US 20170327469 teaches bifunctional compounds for degrading proteins (abstract) by binding to E3 ubiquitin ligase and degron (ULM) binding to ubiquitin ligase of structure
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(present claim 7).
a finding that one of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable
One of ordinary skill has the knowledge of preparing heterobifunctional compounds for binding to ubiquitin ligase using various interchangeable structures for dTAG (binding ligand), linker (covalent attachment for dTAG and degron), and degron (structure binding to ubiquitin ligase). The combination of known structures is known to produce heterobifunctional compounds. Such combination of
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(dTAG),
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(linker), and
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(degron) results in Applicant’s elected species which reads on all of the claims reference herein.
For the reasons provided above, the present claims are found to be prima facie obvious over the prior art.
Conclusion
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/SUN JAE YOO/Primary Examiner, Art Unit 1621