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 .
Status of the Claims
The amendments filed 6/15/2026 have been entered.
Priority
In view of Applicant’s filing of a certified English translation of Korean Patent Application 10-2020-0094789, Applicant has been granted the benefit of foreign priority to 7/29/2020.
Response to Arguments
As indicated in the Action mailed on 2/19/2026, Applicant’s elected species, a compound of Formula 1 which is Example 196 as follows:
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,
which reads upon claims 1-6 and 9-11, has been searched and is deemed to be free of the prior art and non-obvious.
Accordingly, in the Action mailed on 2/19/2026, 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). Specifically, the following two species were identified:
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; and
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.
In Applicant’s instant response dated 6/15/2026, Applicant has amended the claims to overcome the rejection under 35 U.S.C. 102(a)(1) based on:
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.
However, given the indefiniteness of the amended claims (discussed below), the rejection under 35 U.S.C. 103(a) based on:
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is MAINTAINED, albeit based on new grounds in view of Applicant’s amendments to the claims.
Additionally, in the interest of compact prosecution, the search has again 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). That species is:
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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 as well as composition claim 11. A rejection to those claims follows.
Since the search has not been expanded beyond the additional species identified above, claims 6 and 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 § 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.
Claims 1-6 and 11 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 is drawn to a compound of Chemical Formula 1 as follows:
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wherein “Linker-B is a linker that connects the moieties on both sides of Linker-B, and B is connected like
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”
As defined by Merriam-Webster Dictionary, the term “like” means “the same or nearly the same (as in appearance, character, or quantity)” or “closely resembling the subject or original”.
As such, the claim is indefinite because it is unclear whether Linker-B connects the moieties on both sides of Linker-B only via C6 or C7 as depicted, or whether Linker-B can additionally connect via C5 or C8, for example, each of which are nearly the same (as in appearance, character, or quantity) and/or closely resembling (i.e., like) linkage at C6 or C7 as depicted.
Accordingly, claim 1 is rejected as indefinite. Dependent claims 2-6 and 11, which do not clarify the indefiniteness of claim 1, are also rejected.
In the interest of compact prosecution, the alternative meanings of “like” are applied and the claims are rejected accordingly.
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 Hwang et al (WO 2018/208123 – based on US 2020/0062730 as the English language equivalent).
As amended, 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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, wherein Linker-B connects the moieties on both sides of Linker-B via C8 of the CRBN ligand – i.e., a wherein Linker-b is connected like (which is understood to entail “nearly the same (as in appearance, character, or quantity)” and/or “closely resembling”)
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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)).
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 Hwang et al, the compound
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(Paragraph 0063) “specifically binds with CRBN protein” (Abstract) – “a kind of E3 ubiquitin ligase... known to have activity to bind to thalidomide and its derivatives, pamolidomide, lenalidomide and the like to attach ubiquitin for substrate proteins” (Paragraph 0061).
Accordingly, it would have been prima facie obvious, based on Hwang 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.
Claims 1-5 and 11 are ADDITIONALLY rejected under 35 U.S.C. 103(a) as being unpatentable over Crews et al (WO 2018/144649; of record) in view of Hwang et al (WO 2018/208123 – based on US 2020/0062730 as the English language equivalent).
As amended, 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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wherein Linker-B connects the moieties on both sides of Linker-B as follows:
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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)).
As such, Crews et al teach a structurally and functionally related compound which differs from the instantly claimed compound in the following ways:
(A) the linker Rn (equivalent to instantly claimed linker B) of PROTAC 30 is connected to the E3 Ubiquitin Ligase binding moiety, or ‘ULM’ at C8 as opposed to C6 as claimed; and
(B) the E3 Ubiquitin Ligase binding moiety, or ‘ULM’ group (and, more specifically, the cereblon E3 Ubiquitin Ligase binding moiety or ‘CLM’ group) of PROTAC 30 is
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as opposed to the instantly claimed
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, which differs from the ULM/CLM group of Crews et al as indicated by arrow.
Yet, as to (A): as discussed by MPEP 2144.09(I), a prima facie case of obviousness may be made when chemical compounds have very close structural similarities to chemical compounds in the prior art, based on “the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties” (quoting In re Payne, 606 F.2d 303 (CCPA 1979)). Significantly, as further stated by MPEP 2144.09(II), citing In re Wilder, 563 F.2d 457 (CCPA 1977), “[c]ompounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties”.
Moreover, as more specifically taught by Crews et al, the linker can connect to the ULM/CLM group at C6:
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(Page 38, Paragraph 0088).
Accordingly, at the time the invention was made, one of ordinary skill in the art would have been motivated to connect the linker Rn (equivalent to instantly claimed linker B) of PROTAC 30 to the E3 Ubiquitin Ligase binding moiety, or ‘ULM’ at C6 as opposed to C8 with a reasonable expectation of success.
And, as to (B): yet, as taught by Hwang et al, the compound
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(Paragraph 0063) “specifically binds with CRBN protein” (Abstract) – “a kind of E3 ubiquitin ligase... known to have activity to bind to thalidomide and its derivatives, pamolidomide, lenalidomide and the like to attach ubiquitin for substrate proteins” (Paragraph 0061).
Accordingly, it would have been prima facie obvious, based on Hwang 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 6 and 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 6 and 9-10, which are directed to the elected species but which do not include the additional species, have not been further examined.
Conclusion
The new grounds of rejection presented in this Office action are necessitated by Applicant’s amendments to the claims. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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.
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
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