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 .
Claims 1-17 and 21-23, submitted on 14 June 2024, represent all claims currently under consideration.
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.
Priority
This application is a 371 of PCT/US2022/053131, filed 16 December 2022, which claims priority to provisional U.S. 63/290,729, filed 17 December 2021. The effective filing date is 17 December 2021.
Information Disclosure Statement
One Information Disclosure Statement (IDS), submitted on 14 June 2024, is acknowledged and has been considered.
Claim Rejections - 35 USC § 112(a)
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 1-17 and 21-23 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Factors to be considered in making the determination as to whether one skilled in the art would recognize that applicant was in possession of the claimed invention as a whole at the time of filing include : (a) Actual reduction to practice; (b) Disclosure of drawings of structural chemical formulas; (c) Sufficient identifying characteristics such as: (i) Complete structure, (ii) Partial structure, (iii) Physical and/or chemical properties or (iv) Functional characteristics when coupled with a known or disclosed correlation between function and structure; (d) Method of making the claimed invention; (e) Level of skill and knowledge in the art and (f) Predictability in the art. While all of these factors are considered, a sufficient number for a prima facie case are discussed below:
The claims are drawn to a bifunctional compound of Formula (I) with a targeting ligand, linker, and degron which represents a moiety that binds an E3 ubiquitin ligase, and is further specified as being one which binds to Von Hippel-Lindau tumor suppressor or cereblon, with structures V1, V2, C1, and C2 specifically claimed. Paragraphs 0043 through 0046 of the specification disclose these E3 ubiquitin ligase binding compounds. However, these do not encompass all possible E3 ubiquitin ligase binding compounds. The artisan would understand functionally what an E3 ubiquitin ligase binding compound does (bind to an E3 ubiquitin ligase); however, without guidance from the specification as to what compounds can be utilized to practice this invention, the artisan would have no reasonable expectation of success as the only way to determine if a compound functions in this way would be through a posteriori testing. It is clear that Applicant is in possession of the specific compounds of examined claims 7 and 9. However, Applicant is not in possession of each and every possible E3 ubiquitin ligase binding compound. Thus, Applicant was not in possession of the entire invention as claimed at the time of filing of the invention.
Claims 1-17 and 21-23 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Factors to be considered in making the determination as to whether one skilled in the art would recognize that applicant was in possession of the claimed invention as a whole at the time of filing include : (a) Actual reduction to practice; (b) Disclosure of drawings of structural chemical formulas; (c) Sufficient identifying characteristics such as: (i) Complete structure, (ii) Partial structure, (iii) Physical and/or chemical properties or (iv) Functional characteristics when coupled with a known or disclosed correlation between function and structure; (d) Method of making the claimed invention; (e) Level of skill and
knowledge in the art and (f) Predictability in the art. While all of these factors are
considered, a sufficient number for a prima facie case are discussed below:
The claims are drawn to a bifunctional compound of Formula (I) with a targeting ligand, linker, and degron which represents a moiety that binds an E3 ubiquitin ligase, and the linker is further defined in paragraph 0047 as “providing a covalent attachment between the targeting ligand and the degron. The structure of the linker may not be critical, provided it does not substantially interfere with the activity of the targeting ligand or the degron”. Applicant defines the linker in paragraph 0048 through paragraph 0051 and is clearly in possession of these linkers. However, Applicant has not defined every possible covalent linker which can be used to practice this invention, and the artisan would not know if a linker does not substantially interfere with the activity of the targeting ligand or the degron without performing a posteriori testing, providing no predictability in practicing this invention. Applicant is in possession of the linkers which have been defined in paragraphs 0048-0051; however, Applicant is not in possession of every possible linker which does not substantially interfere with the activity of the targeting ligand. Thus, Applicant was not in possession of the entire invention as claimed at the time of filing of the invention.
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.
Claim 17 is 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 17 recites the limitation "the bifunctional compound" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claims 1-17 and 21-23 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. Claims 1, 17, and 21 each contain parentheticals (“Linker” and “Degron”). It is unclear if these parentheticals are necessary parts of the invention or merely representative. The Examiner suggests removing these parentheticals as “the linker” and “the degron” each have antecedent basis from the structures provided in each claim. The remaining claims are rejected as depending upon an indefinite claim without resolving the underlying issues of indefiniteness.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 8, 10, 11, 17, and 21-23 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Berlin (US 2022/0395576; Publication Date: 15 December 2022; Priority to 16 April 2021).
Berlin discloses bifunctional compounds which find utility as modulators of B-Cell lymphoma 6 protein (BCL6). The compounds contain on one end a cereblon ligand that binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation and inhibition of target protein. The bifunctional compounds exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein (Abstract). The present disclosure may be used to treat a number of disease states and/or conditions (Paragraph 0253). The description provides therapeutic compositions comprising an effective amount of a compound described herein and a pharmaceutically acceptable carrier, additive or excipient and optionally an additional bioactive agent. The therapeutic compositions as desribed can be of interest for the treatment or amelioration of a disease, e.g., a cancer. In certain embodiments, the disease is lymphoma, B-cell non-Hodgkin lymphomas, large B-cell lymphoma, Burkitt’s lymphoma, follicular lymphoma, intravascular large B-cell lymphoma, B-cell leukemia, B-cell acute lymphoblastic leukemia, chronic myeloid leukemia, non-small cell lung cancer (Paragraph 0254). Compound 67 (Page 115)
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has variable X as N, variable Y as H, the linker as a C1 alkylene with a heterocycle terminating this chain, and the degron as
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.
Claims 1-4, 6-13, 17, and 21-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Berlin (WO 2021/077010; Publication Date: 22 April 2021).
Berlin (See IDS, 14 June 2024) discloses bifunctional compounds which find utility as modulators of BCL6. The bifunctional compounds contain on one end a Von Hippel-Lindau, cereblon, IAP, or MDMH2 ligand that binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation and inhibition of the target protein (Abstract). Pharmaceutical compositions comprising combinations of an effective amount of at least one bifunctional compound in combination with a pharmaceutically acceptable carrier, additive, or excipient, represents a further aspect of the present disclosure (Paragraph 00239). Compounds of the invention include
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(Paragraph 00400);
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(Paragraph 00433);
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(Paragraph 00450);
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(Paragraph 00481);
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(Paragraph 00558);
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(Paragraph 00751);
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(Example 44, Page 591);
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and (Example 70, Page 599). Table 1 (beginning on page 578) contains over 500 compounds, many of which anticipate the compounds of the examined application. These compounds have variable Y as H, X as N, CH, CH2, NR1 with R1 as alkyl, or O, linkers as alkylene chains with terminal substitutions or PEG with terminal substitutions, and identical VHL or cereblon binding ligands as those claimed. Claim 30 is drawn to the use of compositions comprising the compounds of the disclosure for the treatment of cancer associated with BCL6 accumulation or aggregation. Claim 31 further defines the cancer to be several forms of cancer, including leukemia, benign lymphoma, malignant lymphoma, Burkitt’s lymphoma, melanoma, T-lineage acute lymphoblastic leukemia, peripheral T-cell lymphoma, follicular lymphoma, B-cell leukemia, and intravascular large B-cell lymphoma.
Conclusion
Claims 1-17 and 21-23 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.M.R./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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