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
The instant application, filed on 22 December, 2023, is a 371 of PCT/EP2022/066989 filed on 22 June, 2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06, August, 2024 has been considered by the examiner.
The information disclosure statement (IDS) submitted on 17, April, 2024 has been considered by the examiner.
Status of Application, Amendments, and/or Claims
The response filed on 22 December, 2023 has been entered in full. These are the amended claims of the original claim set received on 22 December, 2023. In the amendment, claims 1-15 are cancelled, and claim 16-35 are new. Therefore, claims 16-35 are pending and are the subject of this Office Action.
Claim Rejections - 35 USC § 112
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.
Claim 21 recites the limitation "the mass ratio". A mass ratio is not introduced in the claim ort in claim 16 from which it depends therefore, there is insufficient antecedent basis for this limitation in the claim.
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 16, 17, 19, 20, 22, 24, 27, 26, 29-32, 34, and 35 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Altman et al. (WO2020/132331, of record IDS 04/17/2024).
In regards to claims 16, 26, 27, and 31 Altman anticipates a biocompatible tissue filler comprising a portion of the silk fibroin fragments (moieties) crosslinked to a polysaccharide wherein the cross linking is zero-length cross linking wherein the solvent is water. (pg.21, line 22-pg.22 line 7). Altman defines zero-length cross linking as “cross-linking between two groups on either polymer strands, or the same polymer strand, where the groups react directly with each other, and no additional cross-linking moiety is inserted between them,” and further provides an example of zero-length cross-linking as “cross-linking between a carboxylic acid group and an amine or alcohol, where one of the groups is activated by an activating agent” (pg.80, lines 15-21). Further Altman anticipates a purification step of the tissue filler to remove cross linking agents and unreacted polymers (pg.158, lines 30-31).
In regards to claims 17 and 35 Altman anticipates the silk fibroin fragments have an average weight average molecular weight from about 5 kDA to about 150 kDa and (pg.21, lines 24-25).
In regards to claim 19 Altman anticipates the polysaccharide being hyaluronic acid (pg.22, lines 4-5).
In regards to claim 20 Altman anticipates the hyaluronic acid (polysaccharide) having a molecular weight between 5 kDa to about 5 MDa (pg.62, lines 22- pg.63, line 1).
In regards to claim 21 Altman anticipate various fibroin moieties (A) to polysaccharide moieties (B) mass ratios which fall within the range of 5:1 to 1:20 (A:B) and further list their viscoelastic properties (pg.303, Tables 29 and 30).
In regards to claim 22 Altman anticipates the zero length cross linking can be facilitated by activating agents including carbodiimides, such as 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) (pg.158, lines 11-16).
In regards to claim 24 Altman anticipates that carbodiimide-mediated coupling between carboxylates and alcohol or amine function groups (steps (i) and (ii)) proceeds readily at ambient temperature in aqueous conditions (pg.158, lines 19-21), and further using dialysis for the purification step (pg.158, lines 30-31).
In regards to claim 29 Altman anticipates the filler can be a viscous fluid for injection (pg.231, lines 13-14/ pg.266, lines 23-27).
In regards to claims 30 and 34 Altman anticipates using the filler to treat a condition or other tissue deficiencies, including a thin lip (lip augmentation), facial augmentation, and skin imperfections (pg.253 line 27 – pg.254, line 31).
In regards to claim 32 Altman anticipates that the zero-length cross-linking mediated with carbodiimide-mediated in aqueous solution (typically water) can be used to mediate esterification allows for amidation between lysine side chains of proteins with the carboxylate groups of hyaluronic acids allows for the formation of HA-protein crosslinked hydrogels (pg.158, lines 19-29).
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.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Altman et al. as applied to claim 16 above, and further in view of DeAngelis et al. (WO 2013/149161).
Altman teaches that the biocompatible tissue filler can comprise a glycosaminoglycan selected from a group containing hyaluronic acid, carboxymethyl cellulose, and chondroitin-4-sulfate, or chondroitin-6-sulfate.
Altman fails to teach the heparosan of the claim, however, DeAngelis teaches heparosan is very similar to hyaluronic acid and heparin, but show greater stability in the body due to the lack of degradation enzymes or binding protein in the body to inhibit function (pg.2, lines 25-28).
Thus, Altman discloses a method of making a cross-linked material comprising silk fibroin and an activating agent such as EDC to react the carboxylic acid residues of a polysaccharide with the amino residues of a fibroin and further teaches the polysaccharides can be hyaluronic acid, carboxymethyl cellulose, and chondroitin-4-sulfate, or chondroitin-6-sulfate, and DeAngelis teaches heparosan is an agent very similar to hyaluronic acid with better stability for use in biomaterials for reconstructive and cosmetic procedures. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious try to combine the teachings of Altman and DeAngelis to incorporate heparosan into a mixture of one or more polysaccharides with a reasonable expectation of success to improve the stability of the biomaterial in the body and improve procedure outcomes.
Claims 23, 25, 28, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over Altman et al. as applied to claims 16 and 26 above, and further in view of D’Este et al. (2014) A systematic analysis of DMTMM vs EDC/NHS for ligation of amines to Hyaluronan in water Carbohydrate Polymers 108; 239-246.
Altman fails to teach the activating agent being 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) of claim 23, the activating agent being tirazine based of claim 25(i)(C), the cross-linked materials not comprising (a)-(d) of claim 28, and the activating agent being selected from a list of option in claim 33.
D’Este however in regards to claim 23, 25, and 33 teaches that when compared to EDC/NHS (the standard method of amine ligation to HA and a very well established method for bioconjugation (pg.239, col 2, lines 3-8)) DMTMM (a tirazine based activating agent, and among the list of agent recited in claim 33) was superior to grafting HA in water in an array of moieties, with benefits such as improved yields to equivalent substrate/HA stoichiometric ratios compared to EDC/NHS, reduced quantity of the coupling agent, and no need for buffering (pg.245, col 2, lines 32-41).
In regards to claim 28, D’Este teaches activation of HA with DMTMM does not introduce any of (a)-(d) of the instant application, and further does not use any linkers to introduce one (scheme 1).
Thus, Altman discloses a method of making a cross-linked material comprising silk fibroin and an activating agent such as EDC to react the carboxylic acid residues of a polysaccharide with the amino residues of a fibroin, and D’Este teaches the use of the activating agent DMTMM (a tirazine based agent) is superior to the standard method EDC/NHS in an array of moieties. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious try to combine the teachings of Altman and D’Este to simply substitute the activating agent EDC with DMTMM with a reasonable expectation of success to improve the yield of cross-crosslinked material without having to use more activating agent.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DASIA A ALDARONDO whose telephone number is (571)272-1977. The examiner can normally be reached on Monday-Thursday from 8am to 6pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at telephone number (571)272-2911. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
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/D.A.A/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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