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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission of RCE on 7/1/26 and the amendment of claims has been entered.
Election/Restrictions
Applicant’s election without traverse of Group II, claimed in claims 11-16 and 21-23 in the reply filed on 6/6/25 was previously acknowledged. Election was made of XBIR3 and Penetratin1.
In the reply filed 1/22/26, Applicants canceled claims 1, 5-10, 12 and 21. Claims 11, 13, 14 and 22 were amended.
In the reply filed 7/1/26, Applicants amended claims 11 and 23. Claim 24 was added
Claims 11, 13-20 and 22-24 are pending.
Claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claim 11, 13-16 and 22-24 read on elected Group II and elected species and are under consideration.
Claim Objections-Withdrawn
The objection to claims 11 and 23 is withdrawn due to amendment of the claim
Claim Rejections - Withdrawn
The rejection of claims 11, 13-16 and 22-23 under 35 U.S.C. 103 as being unpatentable over Troy et al. (US 2015/0165061) is withdrawn due to Applicants arguments.
Claims 11, 13-16 and 22-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,857,609. Although the claims at issue are not identical, they are not patentably distinct from each other is withdrawn
The rejection of claims 11, 13-16 and 22-23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 12-15 and 17-25 of copending Application No. 18/258,796 (reference application) in view of Troy et al. is withdrawn.
Response to Arguments
Applicant’s arguments, filed 7/1/26 , with respect to the Troy et al. reference have been fully considered and are persuasive. The 103 rejection of Troy et al. has been withdrawn. New grounds of rejection are presented below.
Claim Rejections - 35 USC § 103-NEW
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 11, 13-16 and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Troy et al. (US 2015/0165061) in view of Chen et al. (Sci Rep. 2019 May 15; 9:7428) and Shiozaki et al. (Molecular Cell, Vol.11, Issue 2, Feb. 2003, pp. 519-527).
With respect to claim 11, Troy et al. teach and claim XBIR3 linked to Penetratin1 via a disulfide linkage ([0058,0116], claims 8-9), meeting the limitations of claim 11 (in part). Troy et al. teach the conjugates in pharmaceutically acceptable carriers, excipients or diluent [0081]. Troy et al. teach XBIR3 is a caspase 9 inhibitor and meets the limitations of claim 13. Penetratin 1 is a cell penetrating peptide and meets the limitations of claim 14. With respect to the limitation “a plurality…”, while not specifically disclosed as a “plurality” of conjugates, one of ordinary skill in the art would immediately recognize that the disclosed material is necessarily present as a plurality of conjugate molecules. Standard synthesis, purification and formulation yield compositions comprising many copies of a conjugate.
With respect to claim 15, Troy et al. teach and claim Penetratin1-XBir3 ([0058,0116]claims 8-9) via disulfide linkage.
With respect to claim 16, Troy et al. teach the conjugate is formulated for inhalation [0079].
Troy et al. does not teach the conjugate molecules have a concentration greater than 1 mM. However, Troy et al. is suggestive of the limitation.
With respect to the concentrations in claims 11 and 23-24, the concentration of an active agent in a formulation is a result-effective variable and the determination of the optimum or workable ranges of said variable maybe characterized by routine experimentation (Please see MPEP 2144 II-Optimization of Ranges). In the instant case, Troy et al. teach and claim the conjugates at a concentration of 0.01 μM to 1000 μM (claim 12). Troy et al. also teach the quantity of the caspase-9 signaling pathway inhibitor or membrane-permeable conjugates thereof that is administered to a cell, tissue, or subject should be an amount that is effective to inhibit the caspase-9 signaling pathway member within the tissue or subject. This amount is readily determined by the practitioner skilled in the art. The specific dosage employed in connection with any particular embodiment of the present invention will depend upon a number of factors, including the type inhibitor used, the caspase-9 signaling pathway member to be inhibited, and the cell type expressing the target. Quantities will be adjusted for the body weight of the subject, and the particular disease or condition being targeted. It would have been obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize the concentration, to arrive at the concentration of claims 11 and 23-24.
Troy et al. does not teach the conjugate molecules having no more than 40% caspase inhibitor dimers. However, the teachings of Chen et al. and Shiozaki et al. cure this deficiency.
Chen et al. teach the BIR3 domain of XIAP undergoes intermolecular disulfide mediated dimerization. Chen et al. teach that BIR3 contains a solve exposed Cys351 residue and oxidation of Cys351 results in a disulfide bond between two BIR3 molecules (p. 5 and Fig. 3). Chen et al. teach that BIR3 dimeric stated can be revered by treatment with DTT. Chen et al. teach that BIR3/CU(II) reaction mixture, after treatment with DTT exhibited an SEC elution time similar to that of free BIR3 (See Fig. 3). Thus, the amount of BIR3 dimer is a property known to be affected by the reducing agent treatment.
Shiozaki et al. teach the crystal structure of caspase-9 in an inhibitory complex with the BIR3 domain of XIAP and teach that the BIR3 domain forms a heterodimer with caspase-9 monomer. Shiozaki et al. further teach that the surface of caspase-9 interacts with BIR3 is the same surface that mediates caspase-9 homodimerization. Shiozaki et al. demonstrates that monomeric caspase-9 is catalytically inactive and concluded that XIAP sequesters caspase-9 in monomeric states, thereby preventing its catalytic activity (Abstract).
With respect to claims 14 and 22 and the limitations “has no more than 40% caspase inhibitor dimers” (claim 14) and “has no more than 10% caspase inhibitor dimers” (claim 22), it would have been obvious to one of ordinary skill in the art to treat the XBIR3 of Troy et al. with DTT in order to reduce the formation of intermolecular disulfide-linked XBIR3 dimerization because Shiozaki et al. teach that the BIR3 domain of XIAP performs its caspase-9 inhibitory function through direct interaction with caspase-9 at the caspase-9 dimerization interaction. There is a reasonable expectation of success given that Chen et al. demonstrated DTT treatment reverses intermolecular disulfide-linked BIR3 dimerization.
Importantly, the percentage of caspase inhibitor dimers is a result-effective variable and the determination of the optimum or workable ranges of said variable maybe characterized by routine experimentation (Please see MPEP 2144 II-Optimization of Ranges). In the instant case, Chen et al. teach that BIR3 dimer population is affected by reducing with DTT, thereby establishing it as a result driven variable. It would have been obvious and routine experimentation to a person of ordinary skill in the art with a reasonable expectation of success to optimize DTT treatment to reduce the dimer population to a desired level including nor more than 40% or 10%, meeting the limitations of claims 11 and 22.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TARA L MARTINEZ whose telephone number is (571)270-1470. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/TARA L MARTINEZ/Primary Examiner, Art Unit 1654
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