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 .
Information Disclosure Statement
Three information disclosure statements (IDS) submitted: one on 04/05/2023; one on 09/13/2024; and one on 04/03/2025. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The use of the term Capsase-Glo®, for example, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
While the Examiner has made every attempt to check the Specification for trade mark compliance, Applicant is required to carefully check the entire Specification for any and all issues regarding trade mark use compliance.
The disclosure is objected to because of the following informalities: The unit of mass “daltons” should be lower case.
Appropriate correction is required.
Election/Restrictions
Applicant’s election without traverse of the E3ULB species below in the reply filed on 01/08/2026 is acknowledged.
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Wherein the C-1 connector is -CH2-NH- and the L1 linker is
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. The elected invention reads on claims 1-4, 37-40, and 47-48. The elected compound was found to be free of the prior art, therefore, the search was expanded to encompass the any aromatic 1,2-diol L1 linker element and any C1 connector.
Claims 29-30, 49-50, 51-52, and 54-56 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/08/2026.
Status of the Claims
Claims 1-4, 29-30, 37-40, 47-52, and 54-56 are pending in this application. Claims 5-28, 31-36, 41-46, 53, 57-64 have been cancelled by applicant. Claims 1-4, 37-40, and 47-48 are under examination herein. Claims 29-30, 49-52, and 54-56 are withdrawn from consideration.
Claim Objections
Claim 1 is objected to because of the following informalities:
The comma after “300 µM” should be removed.
The “Daltons” after 800 should be lowercase.
The comma after “420 daltons” should be removed.
Appropriate correction is required.
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.
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 37 and 39 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 37 is indefinite because it reads: “R1 to R4 can independently be…” The “can be” language raises a question as to whether it is or isn’t. Examiner suggests rewording to read: “R1 to R4 are independently…”
Claim 39 is indefinite because it reads: “R3 to R6 may optionally be…” The “may be” language raises a question as to whether it is or isn’t. Examiner suggests rewording to read: “R1 to R4 are optionally…”
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.
Claims 1-3, 37-40, and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al. (WO 2019/152440 A1) (“Zhou”).
Regarding claims 1-2 and 47, Zhou discloses their “therapeutically useful” compounds A-L-B of Formula I, wherein A (corresponding to instant L1) is a BRD9 binding moiety, L (corresponding to instant C1) is a linker, and B is a degradation moiety (corresponding to instant E3ULB) (page 5, lines 12-end). Zhou teaches their B can have the structure 1a below (page 6, bottom).
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Zhou discloses their linker (connector C1) has Formula II below (page 8), wherein f-k can be 0 or 1; A1 can be a bond to A and A2 is a bond to B; B1-4 are C1-2 alkyl, optionally substituted with -C-, -S-, -NH-, etc.; C1-2 can be -C(O)-; and D can be alkyl; with some preferred embodiments having the structures II-a-c below (page 9).
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(II-a)
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(II-b)
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(II-c)
Zhou discloses their A BRD9 binding moiety can have the structure E-a below, wherein R22-23 can be H, alkyl, etc.; R24 can be halogen, alkyl, etc.; R25 can be alkyl, hydroxyl, amino, etc.; and s and s’ can be 0, 1, 2, etc. (page 9, bottom)
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Zhou specifically discloses the compound D10 below as a preferred embodiment – labeled with the instantly used labels for clarity (page 39, bottom). This compound has a molecular weight (MW) of about 753, reading on the claimed range of 150-800 daltons, and the linker element corresponding to instant L1 has a MW of about 296, also reading on the claimed range of 54-420 daltons. While Zhou does not specifically disclose an embodiment in which their group corresponding to instant L1 is an aromatic diol (as in the elected species), Zhou teaches 1,2 dimethoxy-phenyl group in the compound below and discloses that in their Formula E-a- (which corresponds to instant L1 in their Formula A-L-B) R25 may be hydroxy and s may be 2. Thus, Zhou discloses a relatively narrow subgenus of the instantly claimed genus, which reads on the instantly elected species.
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Therefore, regarding claims 1-2 and 47, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they are generically embraced by Zhou’s disclosed formula and preferred embodiments; In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). See MPEP 2144.08. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of compounds disclosed by Zhou. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Applicant is advised that H vs. Me is considered an obvious modification in the absence of superior, unexpected results. Note In re Wood 199 USPQ 137; In re Lohr 187 USPQ 548 and In re Bowers 149 USPQ 573. Note also In re Fauque 121 USPQ 425 in which differences were 2H’s vs 2 methyl groups. Also see MPEP 2144.09.
Further regarding claims 47, Zhou’s compound above reads on the at least the compounds below, for the reasons outlined above, when X is O and n = 0.
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and
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Regarding the limitations “wherein E3ULB” has a dissociation constant less than 300 µM” or “wherein E3ULB is an E3 ligase binding moiety” or “wherein the E3ULB binds to the CRBN subunit of the CULLIN4A or CULLIN4B” in claims 1 and 47, Applicant is advised that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Note: MPEP 2111.02. Furthermore, Zhou discloses their compound D10 cited above has an inhibitory effect of “+++”, which equates to an IC50 of about 10-100 nM for BRD9 inhibition (Table 5, page 169).
Regarding claim 3, Zhou discloses their compound D10 above, which reads on the instant claims when instant R4 binds to -C1-E3ULB; R2 is heteroaryl; and R1,3 are H.
Regarding claims 37-38, Zhou discloses their L (corresponding to instant C1) can have the structure II-c above, which read on instant
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when m is 1. While the instantly disclosed preferred embodiment of L shows a methylene between -NH- and Z1, Zhou teaches that in their linkers of Formula II, g, h, i, j, and k can be 0; leaving A1-B1-D-A2, wherein A1 (corresponding to Z2) can be a bond to B (which corresponds to instant E3ULB) and A2 (corresponding to Z1) is a bond to A (which corresponds to instant L1); B1 can be N; and D can be -CH2-. Therefore, one having ordinary skill in the art would have found the claimed C1 “connectors” prima facie obvious, since they are generically embraced by Zhou’s disclosed formula for their linkers and preferred embodiments. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of linkers/ connectors disclosed by Zhou. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Applicant is advised that compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977).
Regarding claims 39-40, Zhou discloses their L (corresponding to instant C1) of Formula II, wherein i, j, and k can be 0; leaving A1-B1-C1-B2-D-A2, wherein A1 (corresponding to Z2) can be a bond to B (which corresponds to instant E3ULB) and A2 (corresponding to Z1) is a bond to A (which corresponds to instant L1); B1 can be C2 heteroalkyl (reading on -NH-CH(CH3)-, as in preferred embodiment II-a shown above); C1 can be a -C(O)- (as in preferred embodiment II-a shown above); B2 can be -NH-; and D can be -CH2-; all reading on instant
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. Therefore, one having ordinary skill in the art would have found the claimed C1 “connectors” prima facie obvious, since they are generically embraced by Zhou’s disclosed formula for their linkers and preferred embodiments. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of linkers/ connectors disclosed by Zhou. Accordingly, one having ordinary skill in the art would have been motivated to prepare any of the compounds embraced by the disclosed generic formula, including those encompassed by the claims.
Applicant is reminded that compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.
Claims 1-4, 37-40, and 47-48 are rejected under 35 U.S.C. 103 as being unpatentable over Muller et al. (WO 2009/145899 A1) (“Muller”); in view of Meanwell et al. (J. Med. Chem. 2011, 54, 2529–2591) (“Meanwell”).
Regarding claims 1-4 and 47-48, Muller discloses their “therapeutically useful” compound below in methods of treating cancer (pages 1-2) – which is the same intended use of the compounds of the instant invention.
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(page 12, top left)
While Muller does not disclose their compounds wherein the group corresponding to instant L1 is an aromatic 1,2 diol; the teachings of Meanwell are relied upon for these disclosures.
Meanwell teaches that the design of bioisosteres frequently introduces structural changes that can be beneficial depending on the context, with size, shape, electronic distribution, polarizability, dipole, polarity, lipophilicity, and pKa potentially playing key contributing roles in molecular recognition and mimicry. In the contemporary practice of medicinal chemistry, the development and application of bioisosteres have been adopted as a fundamental tactical approach useful to address a number of aspects associated with the design and development of drug candidates (abstract). Meanwell teaches -Cl and -OH and monovalent bioisosteres (Table 1, page 2529, col. 1).
Therefore, regarding claims 1-4 and 47-48, one having ordinary skill in the art would have found the claimed compounds prima facie obvious, since they encompass Muller’s compound in view of Meanwell. The requisite motivation for arriving at the claimed compounds stems from the fact that they fall within the generic class of “therapeutically useful” compounds for the treatment of cancer disclosed by Muller, in view of Meanwell’s teaching that -Cl and -OH are classical monovalent bioisosteres, rendering their substitution for one another a routine modification in medicinal chemistry. Accordingly, one having ordinary skill in the art would have been motivated to prepare Muller’s compound wherein the -Cl’s have been replaced by ‘OH, in view of Meanwell.
Further regarding claim 47, the compound below is particularly obvious in view of Muller in view of Meanwell’s disclosure when X is O.
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Further regarding claim 48, the compounds below are particularly obvious in view of Muller in view of Meanwell’s disclosure:
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Further regarding claim 48, Applicant is advised that a novel useful compound that is isomeric with the prior art compound is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compound. In re Norris, 179 F.2d. 970, 84 USPQ 458 (CCPA 1970). Therefore, it would have been obvious to one of ordinary skill to expect similar properties of structurally similar compounds since they are suggestive of one another. It has been held that a compound, which is structurally isomeric with a compound of the prior art, is prima facie obvious absent unexpected results. In re Finely, 81 USPQ 383 (CCPA 1949); 84 USPQ 458 (CCPA 1950).
Regarding the limitations: “wherein E3ULB has a dissociation constant less than 300 µM” or “wherein E3ULB is an E3 ligase binding moiety” or “wherein the E3ULB binds to the CRBN subunit of the CULLIN4A or CULLIN4B” in claims 1 and 47-48, Applicant is reminded that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Regarding claims 37-38, Muller discloses their compound above wherein the group corresponding to instant C1 is
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.
Regarding claims 39-40, Muller discloses their compound above wherein the group corresponding to instant C1 is
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, when n is 0.
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 1-4, 37-40, and 47-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 30-31, 40-41, 47, 53, and 55 of copending Application No. 18/020,019 (Copending ‘019). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 1-4, 37-40, and 47-48, Copending ‘019 claims a composition comprising the instant compounds of Formula E3ULB-C1-L1, including the elected species below: (at least in Copending ‘019 claims 1 and 41).
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 37-40, and 47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 29 of copending Application No. 18/269,122 (Copending ‘122). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claims 1-3, 37-40, and 47, Copending ‘122 claims a compound of Formula I below, reading on the instant compounds when: Degron is a E3 ubiquitin ligase, Q is a bond, R2 is -OH, and n1 is 2 (at least in Copending ‘122 claims 1 and 29).
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Degron is
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This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627