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 .
Drawings
The drawings are objected to because they are in grey ink, specifically Figures 2c, 3d, 3e, 5, and 7 are difficult to see the writing. 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 Objections
Claims 1, 5, 19, 21, 25, 27, and 30 are objected to because of the following informalities:
Claim 1 states “A compound of Formula (I):”, should state “A compound of Formula (I)”
Claim 1 states “or a pharmaceutically acceptable salt thereof; wherein:”, should state “or a pharmaceutically acceptable salt thereof, wherein”
Claim 1 states:
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There should be an additional comma after the second compound.
Claim 5 states “or a pharmaceutically acceptable salt thereof; wherein:”, should state “or a pharmaceutically acceptable salt thereof, wherein”
Claim 19 should have a comma after the structures, states “j and k, are an integer independently selected from”, should state “, and j and k are an integer independently selected from”
Claim 21 states “The compound of claim 20, wherein j is 1 or 3; and k is 3”, should state “The compound of claim 20, wherein j is 1 or 3, and k is 3”
Claim 25 states “The compound of claim 21, wherein j is 1 and E is”, should state “The compound of claim 21, wherein j is 1, and E is”
Claim 27 states “A method of reducing the eEF1A2 protein level in a cancer cell or tissue, the method comprising”, should state “A method of reducing the eEF1A2 protein level in a cancer cell or tissue, wherein the method comprises”
Claim 30 states “The method of claim 29, wherein the metarrestin targets alter perinucleolar compartment (PNC) prevalence; and/or”, should state “The method of claim 29, wherein the metarrestin targets alter perinucleolar compartment (PNC) prevalence, and/or”
Appropriate correction is required.
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 5-6, 9-10, 16, 27-30, and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Jian (Jin Jian et al., “HETEROBIFUNCTIONAL COMPOUNDS AS DEGRADERS OF EEF1A2”, WO 2022159650 A1, Pub. Date: 2022-07-28), in view of Harki (Daniel Harki et al., “Compounds that Degrade Kinases and Uses Thereof”, WO 2020247537 A1, Pub. Date: 2020-12-10).
Jian discloses “eukaryotic translation elongation factors 1 alpha 2 (eEF1A2) or perinucleolar compartment (PNC)-related metastatic protein degradation / disruption compounds including an eEF1A2 ligand, a degradation / disruption tag and a linker, and methods for use of such compounds in the treatment of eEF1A2-mediated diseases as well as PNC-related diseases” (Abstract).
Jian discloses exemplary types of cancer that could be therapeutically treated by manipulation of eEF1A2 level by degraders/disruptors, as breast, prostate, and pancreas cancers (Pg. 3, lines 14-16).
Jian discloses in Claim 33 a method of treating a subject having a perinucleolar compartment metastatic protein-mediated diseases, treated with the compounds disclosed, wherein the disease is metastatic cancer, selected from pancreatic, colorectal, and advanced breast cancer.
Jian discloses moieties that comprise eEF1A2 ligands that comprise a protein of interest, an E3 ligase, and a linker. Jian discloses compound 130, top left, on pg. 229 of the specification as a compound administered to treat eEF1A2-mediated diseases, and PNC related diseases. Compound 130 disclosed in Jian, overlaps with instant Formula (I), top right. To map compound 130 disclosed in Jian, with instant Formula (I), A is a 6 membered cycloalkyl with a hydroxide substituent, bottom left, and E is the group selected below, in the bottom right.
Compound 130 disclosed in Jian
Instant formula (I)
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A
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[AltContent: roundedrect] Compound 130 disclosed in Jian, does not teach a linker of instant Formula (I).
Harki discloses compounds and pharmaceutical compositions that target cyclin D1 in concert with CDK4/6 inhibition to treat ovarian cancer cells [0020]. Harki discloses breast, prostate, lung, colon, and pancreas cancers as embodiments for cancers treated with the disclosed compounds [0067].
Harki discloses Formula I (Pg. 13), bottom left, and compound 1 (Pg. 15), bottom right. The protein of interest disclosed in Harki, is the same protein of interest disclosed in Jian, and the linker disclosed in Harki, is disclosed in instant Claim 1.
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It would have been prima facie obvious for one of ordinary skill in the art, before the effective filing date, to take the known strategy of administering eEF1A2 ligand moieties for treating cancer, as disclosed in Jian, and substitute the linker disclosed in Harki, because Harki also discloses moieties administered for treating cancer, one of ordinary skill would be motivated to substitute one known linker for another as a suitable alternative to arrive at the claimed invention.
Regarding Claim 16, Harki discloses compound 1, see above, that has a C6 alkyl chain in the linker, while the compound in instant Claim 16 contains a C5 alkyl chain in the linker, bottom left. Harki discloses that the general formula for the linker, bottom right, where g is an integer from 1 to 20 (Pg. 10, [0034]).
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It would have been prima facie obvious, for one of ordinary skill in the art before the effective filing date, to change the alkyl chain length in the linker disclosed in Harki, to arrive at the compound of instant Claim 16, because Harki teaches that the linker modification can be made. One of ordinary skill would be motivated to try different chain lengths of linkers to arrive at the claimed invention, because it is known in the art to vary the length of the linker in a moiety, and Harki teaching that g can be 0 to 20, shows that the length of the linker from 0 to 20, is interchangeable and has comparable activity.
Allowable Subject Matter
Claims 18-22, and 25 are free of the prior art.
Closest Prior Art
The closest prior art is Jian (Jin Jian et al., “HETEROBIFUNCTIONAL COMPOUNDS AS DEGRADERS OF EEF1A2”, WO 2022159650 A1, Pub. Date: 2022-07-28), in view of Harki (Daniel Harki et al., “Compounds that Degrade Kinases and Uses Thereof”, WO 2020247537 A1, Pub. Date: 2020-12-10).
The teachings of Jian discussed above are incorporated herein.
Regarding Formula (IV) in instant Claim 18, bottom left, Formula 1 disclosed in Jian (Pg. 4), bottom right, overlaps.
Jian does not teach the linker attached to the eEF1A2 ligand, at the same attachment point as in instant Formula (IV), Jian does not teach R1 substituents as unsubstituted 6 membered cycloalkyl groups, and Jian does not teach a linker that is in the instant Claims.
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Harki discloses compound 1, see above, with the same protein of interest disclosed in Jian, and the linker disclosed in Harki, is the same linker in instant Claim 1.
There is no motivation known in the art, to take compound 103 disclosed in Jian, remove the -OH substituent on the 6 membered cycloalkyl, and substitute with a linker attached to the E3 ligase, while also substituting the linker, with the linker disclosed in Harki to arrive at a compound of instant Formula (IV), because more than three modifications to a single compound is not obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIERRA M ROCHELLE whose telephone number is (571)272-9962. The examiner can normally be reached Mon-Fri 8:00-5:00 EST.
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/C.M.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
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