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 .
Status of Claims
Claims 1, 3-5, 41, 91, 93-94, 99-101, 105-108, and 111 are pending in the instant application.
Claims 2, 6-40, 42-90, 92, 95-98, 102-104, 109-110, and 112-125 have been canceled.
Claims 41, 93-94, 105-106, 108, and 111 stand withdrawn as claims directed to a non-elected invention.
Withdrawn Objections/Rejections
Applicant’s amendment is sufficient to overcome the objections to Claims 99 and 101. These objections are hereby withdrawn.
Applicant’s amendment is sufficient to overcome the rejection of Claim 99 under 35 U.S.C. 112(b). This rejection is hereby withdrawn.
Applicant’s submission of a compliant sequence listing is acknowledged. Therefore, the objection to the specification thereof raised in the non-final rejection mailed June 16th, 2025 is overcome and hereby withdrawn.
Applicant’s cancellation of Claim 2 renders the rejection thereof on the basis that it contains an improper Markush grouping of alternatives moot. The rejection thereof is hereby withdrawn.
Applicant’s amendment is sufficient to overcome the rejection of Claims 1-5, 99, and 107 under 35 U.S.C. 102(a)(1). Applicant’s cancellation of Claim 2 renders the rejection thereof moot. The amended requirement of a divalent linker at instant Claim 1 is sufficient to overcome the rejection, as the cited compounds do not employ a divalent linker as described at the instant specification. These rejections are hereby withdrawn.
Claims Rejections – Improper Markush Grouping
The rejection of Claims 1, 3-5, 99-100, and 107 on the basis that it contains an improper Markush grouping of alternatives is maintained and extended to Claims 91 and 101. 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.
At Page 14 of the remarks filed December 15th, 2025, under “Alleged Improper Markush Grouping”, Applicant states that, “Applicant submits that amended claim 1 is directed to Fromula (VII) that shares a single structural similarity and a common use.”
The examiner does not find this persuasive to overcome the rejection.
The Markush grouping of a compound comprising a monovalent cellular component binder covalently bound to a divalent linker further bound to a monovalent targeted autophagy protein binder as recited at Claims 1, 3-5, 99-100, and 107 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:
Amended Claim 1 limits the compounds to which the claims are directed to comprising a monovalent targeted autophagy protein binder of the formula (VII). This is insufficient to define a proper Markush group.
The compound requires a monovalent targeted autophagy protein binder of formula (VII), a divalent linker, and a monovalent cellular compound binder. The breadth of moieties that meet the definition of “cellular component binder” as defined at Page 43, Paragraph 0127 of the instant specification is insufficient to properly define a Markush grouping of structures. The specification defines cellular component binder as “a substance (e.g. a biomolecule, macromolecule, or compound) which is capable of binding a cellular component. In some embodiments, the cellular component binder is a compound (e.g., a compound described herein). In some embodiments, the cellular component binder is capable of binding a protein (e.g., BRD4). In some embodiments, the cellular component binder is capable of binding a protein aggregate. In some embodiments, the cellular component binder is a protein (e.g., antibody, antibody fragment, or receptor), nucleic acid (e.g., siRNA, antisense nucleic acid), aptamer, or compound).”
Formula (VII) is:
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With z1 defined as 0, 1, or 2, and R1’s broad definition including substituted or unsubstituted heterocycloalkyl, cycloalkyl, aryl, heteroaryl, z3 defined as 0-5, and R3’s broad definition including substituted or unsunsubtituted cycloalkyl, heterocycloalkyl, aryl, or heteroaryl, and L5 and L6 further including substituted or unsubstituted cyclic and acyclic moieties, the result is a group of compounds including distinct ring systems that share no significant structural similarity. In view of the breadth of the available monovalent cellular component binders and the breadth of the structurally distinct moieties that read on formula (VII), the grouping is drawn to a selection of compounds that are not obvious variants of each other. The common features of formula (VII) are insufficient to define a common core structure due to the structural variability of compounds that read on the compounds to which Claim 1 is drawn.
Further, as noted in the non-final rejection mailed June 16th, 2025, these compounds do not share a common use. The common use of these compounds is, broadly, to bind a cellular component. As defined at Paragraph 0128 of the instant specification, however, cellular component can be components naturally inside a cell, foreign agents, and include proteins, ions, polysaccharides, lipids, nucleic acids, viruses, and more. This broad array of components by which the instant compounds might bind is insufficient to properly define a common use that flows from a single structural similarity.
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.
The following rejections are necessitated by amendment:
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-5, 91, 99-101, and 107 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to compounds comprising a monovalent cellular component binder covalently bound to a divalent linker further bound to a monovalent targeted autophagy protein binder, wherein the monovalent targeted autophagy protein binder is a monovalent form of formula (VII):
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Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to any compound comprising a monovalent cellular component binder, defined at Page 43, Paragraph 0127 of the instant specification as “a substance (e.g. a biomolecule, macromolecule, or compound) which is capable of binding a cellular component. In some embodiments, the cellular component binder is a compound (e.g., a compound described herein). In some embodiments, the cellular component binder is capable of binding a protein (e.g., BRD4). In some embodiments, the cellular component binder is capable of binding a protein aggregate. In some embodiments, the cellular component binder is a protein (e.g., antibody, antibody fragment, or receptor), nucleic acid (e.g., siRNA, antisense nucleic acid), aptamer, or compound)”, a broadly defined divalent linker, and any moiety of formula (VII), allowing for any of the myriad of moieties satisfying the recited definitions thereof.
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F. 2d 833, 839, 166, USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
Applicant has provided no examples of compounds comprising a monovalent cellular component binder covalently bound to a divalent linker further bound to a monovalent targeted autophagy protein binder, wherein the monovalent targeted autophagy protein binder is a monovalent form of the formula (VII).
Beginning at Page 215, at Table 1 of the instant application, Applicant provides examples of a compound that is a targeted autophagy binder, as recited at instant Claim 1. Beginning at Page 272 of the instant specification, Applicant discloses the synthetic methods by which the compounds of Table 1 were obtained. Beginning at Page 259, Paragraph 0489, Applicant provides examples of formulas the monovalent cellular component binder might have. Beginning at Page 222, Paragraph 0431, Applicant provides examples of what the divalent linker might be. Nowhere, in the instant application, however, has the Applicant disclosed a single example of a compound comprising a monovalent cellular component binder covalently bound to a divalent linker further bound to a monovalent targeted autophagy protein binder of formula (VII), nor has Applicant sufficiently disclosed the methods by which such a compound might be made. Based on the instant application, a person having ordinary skill in the art would not readily understand how a compound that reads on the limitations recited, for example at Claim 1, might be made, nor would a person having ordinary skill in the art readily understand the motivation for selecting a particular monovalent cellular component binder, a specific divalent linker, or a specific monovalent targeted autophagy protein binder of formula (VII).
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP 608.01(p).
MPEP § 2164.01 (a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F. 2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for making these compounds.
Conclusion
Claims 1, 3-5, 91, 99-101, and 107 are rejected.
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.J.B./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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