DETAILED ACTION
Notice of 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
The earliest effective filing date afforded the instantly claimed invention has been determined to be 7/28/2021, the filing date of PCT/KR2021/009832 of which this Application is a U.S. National Stage Application submitted under 35 U.S.C. 371.
Acknowledgment is made of Applicant’s claim for foreign priority based on a prior application filed in Korea on 7/29/2020. However, Applicant has not been granted the benefit of foreign priority because a certified English translation of the foreign application has not been provided.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 10/15/2025 is acknowledged. The requirement is still deemed proper and is therefore made FINAL.
Claims 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election without further specifying traverse of a single species in the reply filed on 10/15/2025 is also acknowledged.
The elected species read upon claims 1-6 and 9-11. Claims 7-8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Expansion of Election of Species Requirement
As indicated above, the elected species, a compound of Formula 1 which is Example 196 as follows:
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,
reads upon claims 1-6 and 9-11.
The elected species has been searched and is deemed to be free of the prior art and non-obvious. Accordingly, the search has been expanded as called for under current Office Markush practice – a compound-by-compound search – to include at least a single additional species (M.P.E.P. § 803.02). In the instant case, two species were identified, those species are:
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wherein R is halogen; A is a C4 cycloalkyl having 4 hydrogen atoms replaced by C1 alkyl; X, Y and Z are each CH; and Linker-B is
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– which reads on pending claims 1-4 and 11; and
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wherein R is halogen; A is a C4 cycloalkyl having 4 hydrogen atoms replaced by C1 alkyl; X and Y are each CH and Z is N; and Linker-B is
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– which reads on pending claims 1-5 and 11.
Since the search has not been expanded beyond the additional species identified above, claims 9-10, which are directed to the elected species but which do not include the additional species, are objected to as indicated below, and have not been further examined.
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.
Claims 1-4 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Takwale et al (Eur J Med Chem 208:112769, published online 8/26/2020).
Claim 1 is drawn to a compound of Formula 1 which embraces the following compound species:
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wherein R is halogen; A is a C4 cycloalkyl having 4 hydrogen atoms replaced by C1 alkyl; X, Y and Z are each CH; and Linker-B is
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– which reads on pending claims 1-4.
Takwale et al teach the instantly claimed compound species (Page 4, Compound 32b).
Accordingly, claims 1-4 are anticipated.
Claim 11 is drawn to a composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
Takwale et al teach that compound 32b was “administered intravenously (IV), intraperitoneally (IP), and orally” (Page 7, Column 2) wherein “[t]he composition of dosing vehicles was 5% DMSO, 52% PEG400, and 3% Tween 80 in water for IV and IP, and 3% Tween8 and 20% PEG400 in water for PO” (Page 16, Column 1).
Accordingly, claim 11 is also anticipated.
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.
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 1-5 and 11 are rejected under 35 U.S.C. 103(a) as being unpatentable over Crews et al (WO 2018/144649; of record) in view of Kley et al (WO 2021/126974, published 6/24/2021 and having priority to 12/16/2020).
Claim 1 is drawn to a compound of Formula 1 which embraces the following compound species:
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wherein R is halogen; A is a C4 cycloalkyl having 4 hydrogen atoms replaced by C1 alkyl; X and Y are each CH and Z is N; and Linker-B is
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– which reads on pending claims 1-5.
Crews et al teach “cereblon E3 ligase binding compounds... which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein” (Abstract), i.e., “proteolysis targeting chimeric (PROTAC) compounds” (Page 5, Paragraph 0013) comprising “an E3 Ubiquitin Ligase binding moiety... or ‘ULM’ group... and a moiety that binds a target protein... or ‘PTM’ group” wherein “[i]n a preferred embodiment, the ULM is a cereblon E3 Ubiquitin Ligase binding moiety (i.e., a ‘CLM’)” (Page 5, Paragraph 0015) wherein “[i]n certain embodiments, the bifunctional compound further comprises a chemical linker (‘L’)” as follows:
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(Page 6, Paragraph 0017).
In particular, Crews et al teach the following PROTAC compound:
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(Page 166, PROTAC 30)
wherein:
the target protein is an androgen receptor (Page 138, Paragraph 0280) and “the PTM is a chemical moiety that binds to the androgen receptor (AR) (ABM)” (Page 139, Paragraph 0298) which is
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(Page 150);
the linker is
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wherein m is 5 and n is 0 (Page 61 and Page 85, Paragraph 0101); and
the CLM is
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(Page 35, Paragraph 0083, ULM (ac); see also Page 38, Paragraph 0088:
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).
As such, Crews et al teach a structurally and functionally related compound which differs from the instantly claimed compound in comprising as the E3 Ubiquitin Ligase binding moiety, or ‘ULM’ group (and, more specifically, the cereblon E3 Ubiquitin Ligase binding moiety or ‘CLM’ group)
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as opposed to the instantly claimed
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group which differs from the ULM/CLM group of Crews et al as indicated by arrow.
Yet, as taught by Kley et al, disclosing “new compounds binding to cereblon and the use thereof for... modulating protein degradation” (Paragraph 0006), the structure
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(Page 7, Paragraph 0012) is “a compound that binds to an E3 ubiquitin ligase” (Page 6, Paragraph 0012).
Accordingly, it would have been prima facie obvious, based on Kley et al, to utilize
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in place of
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as the ULM/CLM in PROTAC 30 taught by Crews et al to arrive at the instantly claimed compound with a reasonable expectation of success. The simple substitution of one known structure which functions as an E3 Ubiquitin Ligase binding moiety, or ‘ULM’ group (and, more specifically, a cereblon E3 Ubiquitin Ligase binding moiety or ‘CLM’ group) in place of another structure which functions as an E3 Ubiquitin Ligase binding moiety, or ‘ULM’ group (and, more specifically, a cereblon E3 Ubiquitin Ligase binding moiety or ‘CLM’ group) is prima facie obvious.
As such, claims 1-5 are rejected as prima facie obvious.
Claim 11 is drawn to a composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
Crews et al teach “a composition comprising an effective amount of a bifunctional compound of the present disclosure, and a pharmaceutically acceptable carrier” (Page 434, Paragraph 01264).
As such, claim 11 is also rejected as prima facie obvious.
Claim Objections
Claims 9-10 are objected to as depending from a rejected base claim. Since the search has not been expanded beyond the additional species identified above, claims 9-10, which are directed to the elected species but which do not include the additional species, have not been further examined.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CRAIG D RICCI whose telephone number is (571) 270-5864. The examiner can normally be reached on Monday through Thursday, and every other Friday, 7:30 am - 5:00 pm ET. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached on (571) 272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CRAIG D RICCI/
Primary Examiner, Art Unit 1611