--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 .
Applicant’s response dated August 15, 2025 is acknowledged.
Priority
This application is a continuation of 16/341,726 filed on 04/12/2019, which is a 371 of PCT/IB2017/056342 filed on 10/13/2017, which claims benefit in provisional application 62/407,650 filed on 10/13/2016.
Claims Status
Claims 1-14 are pending. Claims 2-5 and 7-14 are withdrawn. Claims 1 and 6 are examined.
Election/Restriction
Applicant’s election with traverse of Group I (Claims 1-8 and 11-14), drawn to a hydrogel in the reply filed on August 15, 2025, is acknowledged. Applicant’s election of the hydrogel of claim 1, further comprising fibrinogen as a species of the invention of group I, is acknowledged. The elected species reads on claims 1 and 6.
The traversal is on the grounds that there is a lack of serious search burden and based on the scope of claims permitted in a pioneering invention.
Applicant’s arguments were fully considered, however they were found unpersuasive.
The restriction requirement is maintained because applicant did not persuasively argue that there would not be a serious search burden in examining all of the claims. Pages 4 and 6 of the restriction requirement explain in detail why there is a serious search burden in examining both groups of inventions and all claimed species. Applicant’s arguments based on pioneering invention in patented parent application are not persuasive because that is not the standard for restriction requirement.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 2-5 and 7-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being withdrawn to a non-elected invention, and non-elected species of the invention, there being no allowable generic or linking claims. Please note that after a final requirement for restriction, the Applicants, in addition to making any response due on the remainder of the action, may petition the Commissioner to review the requirement. Petition may be deferred until after final action on or allowance of claims to the invention elected, but must be filed not later than appeal. A petition will not be considered if reconsideration of the requirement was not requested. (See § 1.181.).
Response to the restriction requirement of June 24, 2025 was timely filed.
Claims 1 and 6 are examined on the merits.
Claim Rejections – 35 USC § 103
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.
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.
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.
Claims 1 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Altschuler (WO 2013/171736 A1, published November 21, 2013) and D’Este (Carbohydrate Polymers, 108 (2014) 239-246).
The claims encompass a hydrogel comprising collagen or collagen like peptide, wherein the collagen or CLP is crosslinked into a network using DMTMM as the crosslinker, and wherein CLP is not conjugated to PEG.
The teachings of Altschuler are related to biomatrix hydrogels and methods of their use (Title). In some embodiments, the hydrogel comprises crosslinked collagen, fibrinogen, among others, and a combination thereof (paragraphs 0032 and 0159). Formulations 5 and 6 describe hydrogels comprising collagen and fibrinogen (paragraph 00365 and 00367). Combinations with covalently crosslinked collagen gel are prepared using crosslinking agents such as EDC and NHS (paragraphs 00366 and 00367).
Altschuler does not teach using DMTMM to crosslink the collagen.
The teachings of D’Este are related to a systemic analysis of DMTMM vs. EDC/NHS for ligation of amines to hyaluronan in water (Title). The activation f carboxyl groups with EDC/NHS for amide formation is the standard method for amine ligation to HA, and a very well established wide-ranging bioconjugation method. The purpose of the analysis is to compare DMTMM to EDC/NHS activation chemistry for HA ligation using an array of substrates. For all the substrates tested DMTMM yields were superior a parity of feed ratios. DMTMM chemistry resulted in effective also in absence of pH control, which is essential for EDC/NHS conjugation. DMTMM-mediated ligation is a new promising chemical tool to synthesize HA derivatives for biomedical and pharmaceutical applications (Abstract). Scheme 1 shows the mechanism of activation of carboxylic acid group on HA followed by coupling to an amine containing compound R-NH2 where the coupling results in the formation of an amide linkage between the HA and the R. DMTMM is soluble and stable in water for an extended period of time. This feature is unique compared to EDC/NHS. DMTMM does not display degradation at room temperature in water, with 100% recovery after 3 hours. DMTMM does not require pH control, which is more practical because it reduces the quantity of chemicals to be used and disposed and simplifies the purification steps. These aspects are a clear advantage for lab and industrial scale production of HA derivatives (page 242 left column). Conclusion section in paragraph bridging pages 245-246 summarizes the benefits of using DMTMM relative to EDC/NHS.
The teachings of Altschuler and D’Este are related to methods of conjugating biopolymers via carboxylic acid group activation with EDC/NHS, and it would have been obvious to have combined them because they are in the same field of endeavor. It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have formed a hydrogel comprising fibrinogen and crosslinked collagen, with a reasonable expectation of success because Altschuler teaches a hydrogel comprising fibrinogen and crosslinked collagen. It would have been obvious to have crosslinked the collagen using EDC/NHS because Altschuler teaches that the crosslinked collagen is obtained by reacting collagen in the presence of EDC/NHS. It would have been obvious to have modified Alschuler’s collagen crosslinking method by replacing EDC/NHS with DMTMM, with a reasonable expectation of success because D’Este teaches that DMTMM is useful for conjugating biopolymers such as hyaluronic acid by activating the carboxylic acid group where the activated carboxylic acid group subsequently reacts with an amine containing compound to create an amide linkage thereby conjugating the amine compound to the hyaluronic acid. The skilled artisan would have understood that collagen crosslinking with EDC/NHS occurs by activation of carboxylic acid groups followed by reaction of activated carboxylic acid groups with amine groups on the collagen thereby forming a crosslinked collagen via amide linkages. One of skill in the art would have been motived to replace EDC/NHS with DMTMM teaches that DMTMM is superior to EDC/NHS and the main benefits include no need of pH shifting during the reaction, improved yields at equivalent stochiometric ratios, reduced quantity of coupling agent necessary, and no need for buffering the reaction mixture. Combining prior art references to yield predictable results supports obviousness. 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.
Conclusion
No claims are allowed.
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/ALMA PIPIC/Primary Examiner, Art Unit 1617