DETAILED ACTION
The present application is a domestic application filed 11 February 2024, which is a continuation of US Application No. 17/256,182 (now US Patent No. 11,939,409), filed 25 December 2020, which is a national stage entry of PCT/IL2019/050663, filed 11 June 2019 and claims priority to US Provisional Application No. 62/691,035, filed 28 June 2018.
The preliminary amendment filed 29 December 2025 is acknowledged. Claims 1-16 are pending in the current application. Claims 1-12 and 16 are withdrawn as being drawn to a non-elected invention, see below. Claims 13-15 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 .
Election/Restrictions
Applicant’s election of Group II in the reply filed on 29 December 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
While Applicant has stated newly added claim 16 is part of Group II, claim 16 depends from claim 6, and claim 6 is part of Group I. Thus, claim 16 is not part of Group II.
Thus, claims 1-12 and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election of the compound of formula IIA
PNG
media_image1.png
64
192
media_image1.png
Greyscale
as the second species of norbornene moiety, and the compound of formula IIIB
PNG
media_image2.png
74
244
media_image2.png
Greyscale
as the third species of tetrazine moiety in the reply filed on 29 December 2025 is acknowledged. The compound of formula IIA was searched.
Meyer et al. (Bioconjugate Chemistry, 2015, vol. 27, pp. 47-53; and Supporting Info, cited in PTO-892) teach preparing a compound of formula IIA (see p.11, Supporting info). A carboxyfluorescein derivative of the compound of formula II is then prepared (Norb-CF). Meyer et al. teach using click chemistry to conjugate Norb-CF with tetrazine modified Fab.
While norbornene derivatives of formula IIA were known before the effective filing date of the claimed invention, there is no teaching, suggestion or motivation to use them to prepare crosslinked hyaluronic acid hydrogels. There is no teaching, suggestion or motivation to modify the teachings of Desai et al. (US2017/0189581, cited below) to prepare crosslinked polysaccharide-based hydrogels.
MPEP 803.02 states that if the examiner determines that the elected species is allowable, the examination of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the Markush-type claim with respect to the nonelected species, the Markush-type claim shall be rejected and claims to the nonelected species held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
The species of norbornene moiety has been expanded to include IIG, norbornene methanamine:
PNG
media_image3.png
62
122
media_image3.png
Greyscale
.
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 are rejected under 35 U.S.C. 103 as being unpatentable over Desai et al. (US 2017/0189581, cited in IDS submitted 13 February 2024).
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
PNG
media_image4.png
274
78
media_image4.png
Greyscale
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:
PNG
media_image5.png
210
264
media_image5.png
Greyscale
, to give a polysaccharide norbornene derivative (i.e. formula IIG; see example 2).
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 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):
PNG
media_image6.png
213
221
media_image6.png
Greyscale
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:
PNG
media_image7.png
196
149
media_image7.png
Greyscale
and
PNG
media_image8.png
178
164
media_image8.png
Greyscale
(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 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 are rejected under 35 U.S.C. 103 as being unpatentable over Desai et al. as applied to claims 13-15 above, and further in view of Hammond et al. (US Patent Application Publication No. 2012/0130045, cited in PTO-892).
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 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:
PNG
media_image9.png
312
270
media_image9.png
Greyscale
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.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
Prosecution Insights