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 .
DETAILED ACTION
Election of Species and Status of the Claims
Applicant’s election with traverse of compound I-34 as the single specific compound and prostate cancer as the single specific cancer in the response filed on June 12th 2026 is acknowledged. The traversal is on the grounds that ‘a search for publications relating to the elected species should reveal publications relating to the other species and thus would not impose a serious burden on the office. This is not found persuasive because:
The compound of formula I is not defined by particular structural moieties, but by groups that bind to particular proteins, and a generic linker moiety.
A search for bifunctional molecules with moieties binding to particular proteins would not necessarily, nor even in theory provide results that include moieties binding to other proteins.
Furthermore, applicant has not argued the art presented in the election of species requirement filed on April 13th 2026, wherein unity of invention is broken for the instant application. The election of species requirement is therefore deemed proper and is made FINAL.
Claims 1, 30-36, 65-69, 75, 77-80, 82-83, and 95-101 are pending. Claims 33-36, 66-67, 80, 82-83, and 96 are withdrawn from further consideration as being directed towards nonelected species until a generic claim has been found allowable. Claims 1, 30-32, 65, 68, 69, 75, 77-79, 95, and 97-101 are examined on their merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statement filed on July 8th 2026, September 4th 2025, and March 21st 2025 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
Claim Rejections - 35 USC § 112(b)
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 1, 30-32, 65, 68, 69, 75, 77-79, 95, and 97-101 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 1 and its dependent claims 30-32, 65, 68, 69, 75, 77-79, and 97-101 are indefinite for the phrases “EPL is a moiety that binds to an effector protein selected from mTOR, PLK1, CDK1, CDK2, CDK9, BRD4, AURKA, AURKB, MEK, Src, c-KIT, KIF11, HSP90, tubulin, proteasome, topoisomerase, or HDAC,” “L is a linker,” and “TPL is a moiety that binds to a target protein selected from BTK, androgen receptor protein, and IDH1,” because one of ordinary skill in the art could not reasonably determine the full scope of how the phrase limits the structure of claim 1.
The structural metes and bounds of each particular binding moiety type, nor the complete metes and bounds of the linker portion are not defined either in the claim or in the specification. While several embodiments are provided for each of the binding moiety and linker portions (for example, see specification, paragraph [0081] which provides examples of mTOR binders), these embodiments are only exemplary in nature and do not provide the full metes and bounds of the structures that would be encompassed by the generic structure of claim 1:
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The dependent claims each clarify particular portions of the structure, but none of the dependent claims (outside of claim 95 which defines complete structures) clarifies all three portions. As one of ordinary skill in the art could not reasonably determine the full structural metes and bounds described by the EPL, TPL, and L portions of the compound of claim 1, claim 1 and its dependent claims 30-32, 65, 68, 69, 75, 77-79, and 91-101 are indefinite.
Claim 95 is indefinite for the references to Tables 1 and 2. See MPEP 2173.05(s):
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). See MPEP 2173.05(s).
All claimed chemical compounds are required to be presented as either chemical structures or named compounds.
Claim 1 and its dependent claims 30-32, 65, 68, 69, 75, 77-79, and 97-101 are rejected on the basis that it contains an improper Markush grouping of alternatives. 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 Markush grouping of Formula I 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:
The compounds of Formula I,
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are not related in the sharing of any particular structural moieties, but only in the extremely broad scope of the EPL, L, and TPL moieties, which are only defined to be functional in nature. The EPL moieties are defined only by their ability to bind to mTOR, PLK1, CDK1, CDK2, CDK9, BRD4, AURKA, AURKB, MEK, Src, c-KIT, KIF11, HSP90, tubulin, proteasome, topoisomerase, or HDAC. The TPL moieties are defined only by their ability to bind to BTK, androgen receptor protein, or IDH1. The L moiety is only broadly defined as “a linker.” The breadth of structures encompassed by these entities would not be recognized by one of ordinary skill in the art as a single chemical class and would not be considered to be obvious variants of each other. Furthermore, the class defined by Formula I would not only include moieties known to bind to each of the above proteins, but any number of moieties yet to be discovered which have similar binding capability.
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
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 and 97-101 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sun (Sun et al., PD28-11 NOVEL DRUGS FOR TARGETING HISTONE DEACETYLASE INHIBITOR TO CELLS CONTAINING ANDROGEN RECEPTORS: ANALYSIS OF IN VIVO EFFECTIVENESS AGAINST HUMAN PROSTATE CANCER. Journal of Urology [Internet]. 2016 Apr 1).
Claim 1 is directed towards a bifunctional comprising three moieties:
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wherein the EPL moiety can be an HDAC binding portion, L is a linker, and the TPL moiety can be an androgen receptor binding portion.
Sun teaches four bifunctional compounds comprising an HDAC binding moiety and an androgen receptor binding moiety linked together (Sun, Introduction; Results). Sun thereby anticipates claim 1.
Claim 97 is directed towards a pharmaceutical composition comprising the compound of claim 1. Sun teaches administration of the compounds to mice, which would necessarily occur in such a pharmaceutical composition. Sun thereby anticipates claim 97.
Claims 98-101 are directed towards the treatment of prostate cancer via administration of the compound of claim 1. Sun teaches administration of the compound to mice in order to treat the LNCaP tumor model (i.e. a prostate cancer tumor). Sun thereby anticipates claims 98-101.
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, 30-32, 65, 68, 69, 75, 77-79, 95, and 97-101 are rejected under 35 U.S.C. 103 as being unpatentable over Asangani (Asangani et al., BET Bromodomain Inhibitors Enhance Efficacy and Disrupt Resistance to AR Antagonists in the Treatment of Prostate Cancer. Mol Cancer Res 1 April 2016; 14 (4): 324–331) in view of Han (Han et al., Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer. J. Med. Chem. 24 January 2019; 62 (2): 941–964) and Borsari (Borsari et al., Designing Chimeric Molecules for Drug Discovery by Leveraging Chemical Biology. J. Med. Chem. 12 March 2020; 63 (5): 1908–1928)
Claims 1, 30-32, 65, 68, 69, 75, 77-79, and 95 are directed towards applicant’s elected species of:
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Applicant’s compound is a bifunctional compound consisting of three portions:
A BRD4 binding moiety
A polyethylene glycol linker
An androgen receptor binding moiety
Such bifunctional compounds are considered often to be advantageous over combination treatments as they have more predictable pharmokinetics and pharmacodynamics than the analogous combinations of multiple drugs1.
Regarding the particular moieties of applicant’s compound, Asangani teaches the treatment of prostate cancer via the synergistic combination of the BRD4 inhibitor, JQ1,
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and the androgen receptor inhibitor, enzalutamide (Asangani, Abstract).
JQ1 is equivalent to the BRD4 binding moiety of applicant’s structure. While Asangani does not explicitly teach administration of applicant’s particular androgen receptor binding moiety, one of ordinary skill in the art would have had a reasonable expectation of success in substituting applicant’s androgen receptor binding moiety for enzalutamide, because it is known in the art to be an equally effective androgen receptor inhibitor. See Han, who explicitly defines applicant’s androgen receptor binding moiety (referred to as ARD-69) as a potent replacement for enzalutamide (Han, pg. 942, Figure 2).
While Han and Asangani do not explicitly link the molecules together with a PEG linker, one of ordinary skill in the art would find such a linker commonplace in the field of bifunctional molecules (Borsari, pg. 1909) and be motivated to attach the JQ1 and ARD-69 with such a linker to achieve synergistic results in the treatment of prostate cancer while having more predictable pharmokinetics than if the drugs were administered separately. One of ordinary skill in the art would thereby find applicant’s elected species, and consequently claims 1, 30-32, 65, 68, 69, 75, 77-79, and 95 prima facie obvious.
Claim 97 is directed towards a pharmaceutical composition comprising the compound of claim 1. As the treatment described above would necessarily be administered in a pharmaceutical composition, claim 97 is prima facie obvious.
Claims 98-101 are directed towards the treatment of prostate cancer via administration of the compound of claim 1. As the two binding moieties are demonstrated to synergistically treat prostate cancer (see Asangani and Han, above), the treatment of prostate cancer, and claims 98-101 are prima facie obvious.
Nonstatutory 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, 30-32, 65, 68, 69, 75, 77-79, 95, and 97-101 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 8, 11, 22, 24, 35-37, 46, 49-50, 52, 55, 88, and 114-119 of copending Application No. 19/108,233 (US20260062422A1; reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application teaches bifunctional compounds comprising a portion identical to applicant’s elected BRD4 binding moiety, a portion identical to applicant’s elected androgen receptor binding moiety, and a linker, as well as the treatment of prostate cancer with the compounds.
See applicant’s elected species:
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See reference claim 11:
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See reference claim 35:
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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 and 97-101 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 67-71, and 74-76 of copending Application No. 18/696,145 (US20240408093A1; reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application overlaps with the instant application in that it teaches a compound comprising:
An androgen receptor binding moiety
A linker
A PLK1 binding moiety,
as well as the treatment of prostate cancer with the compounds.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1, 30-32, 65, 68, 69, 75, 77-79, 95, and 97-101 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 9, 11, 24, 35, 41, 44, 48, 50-51, 56, 61, 96-97, 100, 105-106, 110, 114-115, 131-132, 134-135, and 138 of copending Application No. 19/108,242 (US20260109707A1; reference application) in view of Bauer (Bauer et al., Put a ring on it: application of small aliphatic rings in medicinal chemistry. RSC Med Chem. 2021 Jan 7;12(4):448-471) and Brown (Brown, Bioisosteres in Medicinal Chemistry, 2012). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application teaches compounds comprising a BRD4 binding moiety, and androgen receptor binding moiety, and a linker, as well as the treatment of prostate cancer with the compound. Applicant’s elected species, shown below:
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has a BRD4 binding moiety that differs from that of the reference application,
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(reference application, claim 56),
only in the bioisosteric substitution of a chlorine for a fluorine (Brown, pg. 17), as well as the mere changing of connectivity points to the linker.
Applicant’s elected species additionally contains an androgen receptor binding moiety that differs from that of the reference application,
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(reference application, claim 50),
only in the bioisosteric substitution of a cyclobutyl for a cyclohexyl (Bauer, pg. 453) and hydrogens for methyls (Brown, pg. 17).
As one of ordinary skill in the art of drug discovery, would find each of these replacements obvious, applicant’s elected species is considered an obvious variation of the compounds of the reference application.
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 Anthony Seitz whose telephone number is (703)756-4657. The examiner can normally be reached 7:30 AM ET - 5:00 PM ET M-F.
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, Jeffrey Lundgren can be reached at (571)272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANTHONY JOSEPH SEITZ/Examiner, Art Unit 1629
1 For evidentiary support see Schiller (Schiller PW. Bi- or multifunctional opioid peptide drugs. Life Sci. 2010 Apr 10;86(15-16):598-603)
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