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 1-5 and 7-21 are pending in the instant application.
Claim 6 has been canceled.
Election/Restrictions
This action is in response to an election from a restriction requirement filed on December 18th, 2025. There are 20 claims pending and 17 claims under consideration. Claims 17-20 have been withdrawn as claims directed to a non-elected invention. This is the first action on the merits. The present invention relates to a compound of formula (I) as recited at instant Claim 1.
Acknowledgment is made of Applicant’s election of Group I, drawn to Claims 1-5, 7-16, and newly presented Claim 1 and species election of a single species of a compound of formula (I) as
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in the reply received February 18th, 2026. Applicant was silent with respect to whether the elections were made with or without traverse. As such, the examiner has construed this as an election without traverse. Therefore this restriction is considered proper and thus made FINAL.
The elected species has been found to be free of the prior art. Thus, examination was extended to all compounds of formula (I).
Domestic Benefit
Acknowledgement is made of Applicant’s claim for domestic benefit of U.S. Provisional Application No. 63/394,115, filed August 1st, 2022. Claims 1-5, 7-16, and 21, presently under examination, are fully supported by this application and will be evaluated with an effective filing date of August 1st, 2022.
Information Disclosure Statement
The Information Disclosure Statement received March 19th, 2024 has been fully considered by the examiner, except where marked with a strikethrough.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which Applicant may become aware of in the specification.
Drawings
The drawings are objected to because Figures 1A-1C, including compound structures and structure labels, Figures 2A-2E, labels in figures 4A-4D, Figure 6, and the structures and labels in Figure 8 are illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 1-5, 7-13 and 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a compound of formula (I) in which B is defined as
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and in which a linker is present or an unbranched hydrocarbon chain comprising up to 12 atoms, wherein one carbon atom is optionally substituted with oxo and one or more of the carbon atoms is optionally replaced by -O or -NH), does not reasonably provide enablement for compounds of formula (I) in which B is a residue of other compounds, a compound in which the linker is absent, or a compound in which the linker is not as described above. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
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 of formula (I) or a salt thereof.
Breadth of the invention:
The scope of the claimed invention is very broad. At Page 10 of the instant specification, Applicant speculates a linker can comprise 3-500 atoms, including branched or non-branched or cyclic linkers, or combinations thereof. Further, at Page 12, Applicant states B is a residue that binds to BRD4 with at least 10-fold selectivity against the other BET proteins. This could include an array of compounds, both known presently, or compounds discovered years from now that bind selectively to BRD4. Can the Applicant simply “reach through” and obtain patent protection for compounds including residues of molecules that have yet to be discovered, or that are presently known and later demonstrated to selectively bind to BRD4? With the variability of potential linkers and/or residues meeting the definition provided for residue B, a myriad of compounds are readily envisaged for which the Applicant has not instantly demonstrated sufficiently in the instant disclosure.
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:
Beginning at Page 19, several examples of compounds satisfying the limitations of a compound of formula (I) as recited at instant Claim 1. The instant disclosure, however, is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of any compounds, compositions or salts thereof wherein the residue B and the linker were not defined as stated above in the present application.
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 chemical 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 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.
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 1-5, 7-13, and 16 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 recites the limitation “B is the residue of a molecule that selectively degrades BRD4 through its N-terminal bromodomain.” Regarding a molecule that selectively degrades BRD4, beginning at Page 12 of the instant specification, two specific examples of such a molecule are provided, along with the examples stating that a molecule binds to BRD 4 with at least 10-, 100-, or 1000-fold selectivity against other BET proteins. This is insufficient for a person having ordinary skill in the art to readily understand the metes and bounds of this limitation. Further, with regard to the limitation of “residue of a molecule”, at Page 14 of the instant specification, Applicant defines the term “residue” to mean “a compound that has been modified in any manner which results in the creation of an open valence wherein the site of the open valence. The open valence can be created by the removal of 1 or more atoms from the compound (e.g., removal of a single atom such as hydrogen or removal of more than one atom such as a group of atoms including but not limited to an amine, hydroxyl, methyl, amide (e.g., -C(=O)NH2) or acetyl group). The open valence can also be created by the chemical conversion of a first function group of the compound to a second functional group of the compound (e.g., reduction of a carbonyl group, replacement of a carbonyl group with an amine) followed by the removal of 1 or more atoms from the second functional group to create the open valence.” This further renders the aforementioned limitation indefinite, as after a suitable compound that selectively degrades BRD4 is selected, it is unclear to a person having ordinary skill in the art at which position on the molecule modification should occur to generate the suitable residue. Appropriate clarification is required.
Further, with respect to the limitation of L being present as a linker, at Page 10 of the instant specification, the Applicant teaches “The linker can vary in length and atom composition and for example can be branched or non-branched or cyclic or a combination thereof.” Based on this definition, a person having ordinary skill in the art would not readily understand which linkers are appropriate, nor would they understand the motivation for selecting a particular linker. Appropriate clarification is required.
Dependent Claims 2-5, 7-13, and 16 do not clarify these limitations, and therefore are also rendered indefinite.
Allowable Subject Matter
Claims 14-15 and 21 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1-5, 7-13, and 16 are rejected.
Claims 14-15 and 21 are objected to.
No claim is allowed.
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.
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 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