DETAILED ACTION
This Office Action is in response to Applicant’s Amendment and Remarks filed on 03 May 2026 in which claim 13 was amended to change the scope and breadth of the claims, and 17-20 were newly added.
Claims 1-20 are pending in the current application. Claims 1-12 and 16 remain withdrawn as being drawn to a non-elected invention. Claims 13-15 and 17-20 are examined on the merits herein.
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 .
New & Modified Rejections
The following are new ground(s) or modified rejections necessitated by Applicant's amendment, filed on 03 May 2026, where the limitations in pending claim 13 as amended now have been changed and claims 17-20 have been newly added. Therefore, rejections from the previous Office Action, dated 02 February 2026, have been modified and are listed below.
Claim Rejections - 35 USC § 112(b)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 18 and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 18 depends from claim 13 (not claim 14), and recites a compound of formula IIIB and formula IIA, however, the structure of these compounds are not recited in either claim 18 or claim 13.
According to MPEP 2173.05(s), claims are to be complete themselves and only in exceptional circumstances can incorporation-by-reference be made to a specific figure or table. "Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant's convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”.
The recitation “The kit of claim 13, used in the preparation of an injectable gel…” in claim 19, renders the claim herein indefinite. The claim appears to be directed to multiple categories of invention. The claim could be interpreted to be a kit, for use in the preparation of an injectable gel. The claim could also be interpreted to be a method of using the kit. Alternatively, the claim could be interpreted to be an injectable gel composition comprising a polymer prepared from mixing the first and second HA chains of claim 13.
For purposes of examination, the claim is interpreted as being directed to a kit, for preparing an injectable gel. However, the claim does not require an injectable gel.
Response to Arguments
Applicant's arguments filed 03 May 2026 have been fully considered but they are not persuasive.
Applicant contends Desai et al. teaches only 5% crosslinked gel provides optimal balance between strength and volumetric swelling, and that one of ordinary skill in the art would not have been motivated to prepare a hydrogel from polymers having less than 5% degree of modification, because it would have resulted in reduced mechanical strength and increased swelling.
The above arguments are not found persuasive, because Desai et al. teach the crosslinked hydrogels can be used for a variety of purposes including: use as a dermal filler, drug delivery device, wound dressing, postsurgical adhesion prevention, tissue engineering, etc. One of ordinary skill in the art would expect these end products may need to have different desirable mechanical strength and swelling properties. Furthermore, Desai et al. expressly teach the degree of substitution may vary widely, and products having low and high DS can be prepared.
As discussed in the modified grounds of rejection below, the skilled artisan would have been motivated to modify the degree of substitution of tetrazine and/or norbornene along the polymer, because it directly affects the maximum crosslinking density of the desired hydrogel, which in turn affects the swelling capacity of the hydrogel. While Desai et al. exemplify hydrogels prepared from polymers having a 5% degree of substitution (modification), Desai et al. expressly teach this value may be modified to obtain hydrogels having different gelation kinetics. Furthermore, Desai et al. teach broad ranges of substitution, and teaches preparing hydrogels having a low degree of substitution and a high degree of substitution. The ordinary artisan would have been motivated to start at a 5% degree of substitution, and prepare hydrogels from polymers having a higher and lower degree of substitution.
Applicant contends the current application demonstrates unexpected strength and rheological behavior of gels despite their low content. Applicant contends new claim 19 is directed to an injectable gel with superior rheological properties.
The above arguments are not found persuasive. Claim 19 is interpreted as being directed to a kit, which can be used to prepare an injectable gel. Furthermore, Applicant has not discussed how the rheological properties claimed compare with the closest prior art. See MPEP 716.02(e), “An affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness.”.
Applicant has pointed to Table 2 of the present Specification to show the LVR of an injectable gel obtained from mixing the polymers in the kit is unexpectedly superior at low degrees of crosslinking compared to commercially available hydrogels prepared from higher degrees of crosslinking.
The data has been considered, but it is not commensurate in scope with the present claims. The data in the table is directed to an injectable gel having a specific crosslinking ratio, and prepared from specific HA-tetrazine and HA-norbornene derivatives. Furthermore, the degree of crosslinking is limited to 0.6%-1%, while the present claims allow for a degree of crosslinking to range from 0.2 to 4% when the two polymers are crosslinked from a variety of tetrazine and norbornene derivatives. However, the claims are not directed to a crosslinked polymer.
The present claims are directed to a kit comprising the reagents, and not the hydrogel as argued by Applicant.
Applicant contends Desai et al. teach the use of various polymers, with no specific guidance towards hyaluronic acid. Applicant has pointed to Moulonguet et al. for teaching alginate-based gels have been removed from the market due to the occurrence of firm inflammatory modules.
The above argument is not found persuasive, since Desai et al. lists hyaluronic acid as one of ten possible polymers.
With respect to Hammonds, Applicant argues the reference describes a kit having reagents based on alkyne-containing electrophilic reagents and azide-containing, and not two reactive polymers.
The above argument is not found persuasive. Hammond et al. was cited for teaching a kit comprising two reagents that will be reacted together via click chemistry, like the reactive polymers of Desai et al. and the present claims.
The rejection is hereby maintained.
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.
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.
Claim(s) 13-15, 17, 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Desai et al. (US 2017/0189581, cited in previous Office Action).
Desai et al. describe providing a biorthogonal pair of functional groups that react via click chemistry to form crosslinkers that can be used to form biocompatible hydrogels (para [0004]). Desai et al. teach providing a first polymer comprising a tetrazine moiety, and a second polymer comprising at least one norbornene moiety (para [0075]). The first polymer and second polymer comprises a polysaccharide (claim 8). Exemplary polymers include hyaluronic acid (para [0137]; and claim 7).
Desai et al. teach contacting the second polymer with the first polymer forms a cross-linked polymer (para [0077]). In para [0076], Desai et al. show tetrazole moieties covalently bound to a polysaccharide via an amide or ester bond, and norbornene moieties covalently bound to a polysaccharide via an amide or ester bond. The ratio of the second polymer to the first polymer varies, and includes about 1:3, 1:2, 1:1, 2:1 and 3:1 (para [0080]). Desai et al. teach
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as an exemplary tetrazine moiety, and modifying a polysaccharide with it to give a polysaccharide-tetrazine derivative (para [0146]). And Desai et al. teach modifying a polysaccharide with norbornene-5-methanamine:
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, to give a polysaccharide norbornene derivative (i.e. formula IIG; see example 2).
Desai et al. teach crosslinking polymers having a 5% degree of substitution (examples 2 and 3). Gelation kinetics can be tuned by varying the temperature or initial degree of substitution of the click polymers (para [0162]). Desai et al. teach encapsulating cells in hydrogels prepared from a tetrazine-polymer and norbornene-polymer that had low versus high degrees of substitution (para [0169]). For example, each polymer may be substituted with 1-500 norbornene moieties or 1-500 tetrazine moieties (para [0080]). The crosslinking capacity of the polymers has a maximum limit based on the degree of substitution (para [0083]). A higher theoretical crosslinking DS (determined by the DS or ratio of the first polymer:the second polymer) results in a stiffer or more highly crosslinked network of polymers in the hydrogel. They found the cells were viable (minimal cell death) in the click crosslinked gels 4 hours and 3 days after encapsulation (para [0170]).The cells were significantly more viable in the click polymer hydrogels immediately after encapsulation and after 3 days of culture.
Desai et al. teach mixing the polysaccharide-norbornene derivative with the polysaccharide-tetrazine derivative at different ratios to modify the mechanical properties of the hydrogel, for a given polymer concentration between 2 and 4% w/v (para [0163]). They found Young’s modulus increased with increasing polymer concentration, and decreased as the ratio between the polymers deviated from the stoichiometrically balanced norbornene:tetrazine (N:T) ratio of 1. Thus, they teach changing the ratio of the two polymers provides hydrogels of varying stiffness (also see para [0083]). They also found that while the N:T ratio has a significant effect on the swelling ratio, the polymer concentration does not. This indicates that the swelling ratio of the crosslinked polysaccharide is determined by the crosslink density more than the polymer concentration (para [0164]). Desai et al. teach using an 18 G needle (i.e. an injecting device), (example 6). Desai et al. teach the crosslinked polymer can be used as a dermal filler, drug delivery device, wound dressing, postsurgical adhesion prevention, tissue engineering, etc. (para [0148]).
Desai et al. teach preparing a hydrogel comprising a first polymer and a second polymer, wherein the first polymer is connected to the second polymer by linkers of formula (A):
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wherein R1 is a Co-C6 alkyl-NR2N; R2 is a aryl; R3 is -Co-C6 alkyl-NR2N-, -C0-C6 alkyl-O-, -C0-C3 alkyl-C(O); and R4 is heteroaryl (claim 1). Desai et al. disclose formula (I) and (III) as exemplary linkers:
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and
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(claim 1).
The recitation “instructions for mixing the first HA chain and the second HA chain” in claim 13 is broadly and reasonably interpreted to include where Desai et al. teach the steps of mixing a first polysaccharide-tetrazine chain with a second polysaccharide-norbornene chain to produce a polymer having a linker. Thus, the teaching of Desai et al. on preparing the polymer reads on “instructions”.
The recitation “kit” in claim 13 is broadly and reasonably interpreted to include a composition.
Hyaluronic acid is described as one of the preferred polysaccharides. The norbornene derivative of formula IIG is exemplified and a polysaccharide is prepared with it. Similarly, the tetrazine derivative of formula IIIB is an exemplified tetrazine moiety.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide a composition comprising about a 1:1 ratio of a HA-tetrazine with an HA-norbornene, wherein the tetrazine and norbornene have the structure shown above, because Desai et al. teach mixing together a polysaccharide-tetrazine derivative with a polysaccharide-norbornene derivative. Mixing the two functionalized polysaccharide derivatives allows for crosslinking to occur via click chemistry, which is a well-known chemical method to conjugate to molecules together. In this case, the obtained polymer forms a desired crosslinked hydrogel.
The skilled artisan would have been motivated to modify the degree of substitution of tetrazine and/or norbornene along the polymer, because it directly affects the maximum crosslinking density of the desired hydrogel, which in turn affects the swelling capacity of the hydrogel. While Desai et al. exemplify hydrogels prepared from polymers having a 5% degree of substitution (modification), Desai et al. expressly teach this value may be modified to obtain hydrogels having different gelation kinetics. Furthermore, Desai et al. teach a broad ranges of substitution, and teaches preparing hydrogels having a low degree of substitution and a high degree of substitution. The ordinary artisan would have been motivated to start at a 5% degree of substitution, and prepare hydrogels from polymers having a higher and lower degree of substitution.
The ordinary artisan would have been motivated to prepare hydrogel of varying stiffness depending on its intended use as a dermal filler, drug delivery device, wound dressing, postsurgical adhesion prevention, tissue engineering, etc.
The recitation “…thereby obtaining a polymer comprising…via one or more linkers...wherein said polymer is characterized by a crosslinking degree of 0.2 to 4%” in claim 13 necessarily occurs upon performing the instructions.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 13-15, 17, 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Desai et al. as applied to claims 13-15, 17, 19 and 20 above, and further in view of Hammond et al. (US Patent Application Publication No. 2012/0130045, cited in previous Office Action).
Desai et al. teach as discussed above.
Desai et al. do not expressly disclose “a kit” with “instructions” for mixing a first HA chain and a second HA chain (present claim 13).
Hammond et al. is concerned with methods for preparing biomolecule-polymer conjugates of formula I, wherein the biomolecule is a polysaccharide (claim 1). Desai et al. teach a kit for preparing the biomolecule-polymer conjugate, comprising an alkyne-containing electrophilic reagent in a first container, an azide-containing polymer of formula C in a second container, and instructions for use (claim 23). The method of preparing the conjugate relies on click chemistry (para [0098]-[0102]). The instructions include mixing the alkyne-modified biomolecule with an azide-containing polymer (steps 6 and 7 of para [0094]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to provide a kit comprising a HA-norbornene moiety and an HA-tetrazine moiety with instructions on how to prepare a polymer from them.
In the same field of endeavor of preparing a conjugate using click chemistry as Desai et al., Hammond et al. teach providing a kit comprising a container with one molecule modified with a functional group, a container with another molecule modified with a functional group and instructions for mixing the two molecules. Hammond et al. teach upon mixing, the molecules participate in click chemistry to form a bioconjugate. Accordingly, the ordinary artisan would have been motivated to provide a kit having HA-norbornene and HA-tetrazine, with instructions on mixing the two because Desai et al. expressly teach forming a polymer using click chemistry between the norbornene and tetrazine functional groups.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 13-15 and 17-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,939,409 in view of Desai et al., and Hammond et al. (cited above).
The claims of the reference Patent are directed towards a process for preparing the polymer of claim 1, the process comprising mixing a first HA chain comprising a norbornene moiety, with a second HA chain comprising a tetrazine moiety. Claim 5 is directed towards a linker represented by formula:
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The reference Patent do not expressly disclose the tetrazine of formula IIIB, or norbornene of formula IIA or IIG. The reference Patent do not expressly disclose a kit comprising the above.
Desai et al. teach as discussed above.
Hammond et al. teach as discussed above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to mix an HA-norbornene of formula IIG with an HA-tetrazine of formula IIIB, because Desai et al. expressly teach preparing a polymer from one polymer modified with a norbornene of formula IIG, and one polymer modified with a tetrazine of formula IIIB. The norbornene and tetrazine react to form a conjugate/crosslinked polymer via click chemistry.
One having ordinary skill in the art would have been motivated to mix hyaluronic acid modified with a norbornene of formula IIA with hyaluronic acid modified with a tetrazine of formula IIIB in order to arrive at the linker recited in claim 5 of the reference Patent, in accordance with the method described in claims 13-15 of the reference Patent.
In the same field of endeavor of preparing a conjugate using click chemistry as Desai et al., Hammond et al. teach a kit comprising a container with one molecule modified with a functional group, a container with another molecule modified with a functional group and instructions for mixing the two which participates in click chemistry to form a bioconjugate. The ordinary artisan would have similarly provided a kit having HA-norbornene and HA-tetrazine, with instructions on mixing the two because Desai et al. expressly teach forming a polymer using click chemistry between the norbornene and tetrazine functional groups. The claims of the reference Patent also describe a crosslinking reaction between HA-tetrazine and HA-norbornene to form a polymer hydrogel.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the claims of the reference Patent in view of Hammond et al.
Response to Arguments
Applicant's arguments filed 03 May 2026 have been fully considered but they are not persuasive.
Applicant has requested that the provisional rejections be held in abeyance until patentable subject matter is identified.
The obviousness double patenting rejection is hereby maintained.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAHAR A CRAIGO whose telephone number is (571)270-1326. The examiner can normally be reached M-F: Noon-8pm ET.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
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