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 .
Priority
Acknowledgments are made that this application claims the priority to the following:
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Information Disclosure Statement
Filed information disclosure statements (IDS) comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, they have been placed in the application file and the information therein has been considered as to the merits.
Response to Restriction
Applicant's response to restriction requirement and election of group I corresponding to claims 1-26, in the reply filed on 06/18/2026 is acknowledged.
The examiner also acknowledges applicants response to election of species and providing the following species for the claimed conjugate:
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, which falling under the general formula Z-Y1-X-X-Y1-Z (formula V). Claims 1, 13-14, 21 and 23-26 read on the elected species.
Claims 2-12, 15-20, 22 and 27-33 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
The claims 1, 13-14, 21 and 23-26 are examined, in light of elected speices, on merits in this office action.
Claim Objections/Sequence Compliance
Claim 24 and specification are objected to because of the following informalities: 37 CFR 1.821(d) states that where the claims and/or specification recite a sequence with at least 4 amino acids, the sequence identifier (SEQ ID NO) must be included. The applicants need to provide a sequence listing and their corresponding sequence identifiers. 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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 13-14, 21 and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Low (WO2019/232280A1) in view of MacDonald (US7723295B2), Feng (BioMol Concepts, 2016, 7(3), 179-187) and Sela (The FASEB Journal, May 1997, vol.11, 449-456), Guo (Mol Imaging Biol. 2012 December, 14(6), 743-752) and Hoyer (Bellstein J. Org., 2012, 8, 1788-1797).
For claims 1 and 13-14:
Low teaches a compound of formula X-Y-Z, wherein in X is at least one agent that improves bone density, mechanical strength, bone deposition, or quality; Z is at least one bone-targeting molecule; and Y is a linker that joins and/or links X and Z [see 0007].
Low further exemplified compound of formula X-Y-Z, wherein X can be Bone Morphogenic Protein(s) (BMP); Z is 10 aspartic acid residues; and Y is PEG, ranges from 2-8 [see pages 4-5].
Low further teaches that Z, which is 10 Asp residues, which can be attached at N- or C-terminus [see 0148], which has an affinity for bone and helps to direct the conjugate to bone and binds to hydroxyapatite and/or raw bone [see 0007, 0140-0141] and its advantages [see Example 1].
Differences between Low and instant claim(s) are as follows:
(i) Low is silent on applicants X, which has thrombopoietic activity or sirtuin activity;
(ii) Low silent on D-amino acids for 10 Asp residues;
(iii) Low is silent on dimeric form of their compound, X-Y-Z.
With regard to (i) of above, Low suggests that X is at least one agent that improves bone density, mechanical strength, bone deposition, or quality etc., and further suggests that it can be Bone Morphogenic Protein(s) (BMP), Insulin Like Growth Factors (IGF), fibroblast growth factors, peptide, hormones, hormone releasing agents, lactoferrin, Ghrelin, c-Jun N-terminal kinase 3 agonists (FNK3 agonists), vasoactive peptide(s), any growth factor, and any active portion of any growth factor etc. This implied that X is a variable and can be substituted with other divergent proteins or peptides.
In addition to above, MacDonald teaches the following dimeric form of peptide compound, which binds to and activate the thrombopoietin receptor or otherwise act as TPO agonist:
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, wherein X10 is sarcosine or beta-alanine [see col. 4].
The above dimeric form is identical to applicants X-X in the elected species.
In light of above, Low teaches monomeric form, X-Y-Z and advantages of 10D in targeted delivery of active agent (X), whereas MacDonalds teaches applicants claimed active agent, and so, a skilled person in the art would be motivated to incorporate ‘molecule having thrombopoietic activity’ for variable X in X-Y-Z and arrive at applicants monomeric form claimed dimeric conjugate.
With regard to (ii) of above, the following art teaches advantages of D-amino acids:
Feng teaches that D-amino acids enhance biostability of peptides [see sections D-amino acids enhancing biostability and Outlook].
Sela teaches that D-amino acids show high specificity towards immune response play dominant role, and states that D-amino acids may be an advantage in terms of both specificity and efficacy, the later because longer persistence, in an undigested form because they resist enzymatic degradation [see abstract].
Therefore, one would be motivated to replace L-amino acids with D-amino acids.
With regard to (iii) of above, advantages of dimeric peptides over their corresponding monomers are well known in the art, as evidenced from the following art:
Guo teach that the pharmacokinetics of both monomeric and dimeric RGD peptide tracers were compared, and the RGD dimers showed significantly higher binding affinity than monomeric analogs [see abstract].
Hoyer teach that conjugation of a functionalized cymantrene with (sC18)2 leads to significant reduction of its IC50 value in tumor cells compared to the respective sC18 conjugate, proving that dimerization is a useful method to increase the drug-delivery potential of a cell-penetrating peptide [see abstract].
Therefore, a skilled person in the art would be motivated to make the dimeric form in light of its advantages.
For claims 21-23:
Low teaches that Y is PEG, ranges from 2-8 [see pages 4-5].
For claims 24-25:
See For claims 1 and 13-14 above.
For claim 26:
Low teaches pharmaceutical composition of X-Y-Z and differences are explained under For claims 1 and 13-14 above.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants individual components, viz., monomeric form, molecule having thrombopoietic activity, advantages of D-amino acids and dimeric forms etc., were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to combine the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed conjugate of formula (V) with a reasonable expectation of success.
A combination of prior art references is only proper if a person of ordinary skill in the art (POSA) at the time of the invention, faced with the same problem, would have been motivated to combine their teachings with a reasonable expectation of success. See KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007). Here, the technical fields and problems addressed by the references are not distinct from that of the present invention.
The strongest rationale for combining references is a recognition, expressly or impliedly in the prior art or drawn from a convincing line of reasoning based on established scientific principles or legal precedent, that some advantage or expected beneficial result would have been produced by their combination. In re Sernaker, 702 F.2d 989, 994-95, 217 USPQ 1, 5-6 (Fed. Cir. 1983).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
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