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 .
Status of the Claims
Claims 1 – 56 were pending. Claims 1 – 29, 31, 33 – 36, 40, 46 – 56 have been canceled; claims 30, 32, 37 – 39, and 41 – 45 have been amended; and claims 57 – 58 have been newly added. Claims 30, 32, 37 – 39, 41 – 45, and 57 – 58 are currently pending and are the subject of this Office Action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/01/2025 in compliance with the provisions of 37 CFR 1.97 and has been considered by the examiner.
Claim Objections
Previous objection, withdrawn: claims 8 – 29, 36 – 39, 42 – 56 were objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim.
In view of the claim amendments in the reply 10/01/2025, this objection is withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Previous rejection, withdrawn: claims 1 – 7, 30 – 35, and 40 – 41 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
In view of the claim amendments in the reply 10/01/2025, this rejection is withdrawn.
New rejection, necessitated by amendments: claims 30, 32, 37 – 39, 41 – 45, and 57 – 58 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 30 recites “covalently linking a biomolecule to a cryogel, thereby making the modified cryogel; wherein the covalently linking comprises a cycloaddition reaction”. However, the “cycloaddition” reaction is not supported by the present specification.
On page 5, first paragraph, of the reply of 10/01/2025, Applicant states that “[s]upport for the claim amendments and new claims can be found throughout the specification and claims as originally filed. For example, amendments to claim 30 can be found in previous claim 31, Examples 5 and 6, and Figure 6.” However, “cycloaddition” specifically is not adequately described in the specification as filed. New or amended claims which introduce elements or limitations that are not supported by the as-filed disclosure violate the written description requirement. See, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971) (subgenus range was not supported by generic disclosure and specific example within the subgenus range); In re Smith, 458 F.2d 1389, 1395, 173 USPQ 679, 683 (CCPA 1972) (an adequate description of a genus may not support claims to a subgenus or species within the genus). See MPEP 2163(I)(B). Previous claim 31, Examples 5 and 6, and Figure 6 recite broad procedures or broad descriptions that do not define the specific chemical reaction of cycloaddition.
Claims 32, 37 – 39, 41 – 45, and 57 – 58 depend from claim 30, either directly or indirectly, and thus inherit the deficiencies of claim 30.
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.
Previous rejection, withdrawn: claims 7, 34, and 35 were 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.
In view of the cancelation of claims 7 and 34 – 35 in the reply of 10/01/2025, this rejection is withdrawn.
Claim Rejections - 35 USC § 102
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 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.
Previous rejection, withdrawn: claims 1 – 7, 30 – 33, and 40 – 41 were rejected under 35 U.S.C. 102(a)(1)/(2) as being anticipated by MOONEY (WO 2018/026884 A1, published 02/08/2018; see PTO-892: Notice of References Cited of 07/01/2025).
In view of the claim amendments in the reply of 10/01/2025, this rejection is withdrawn.
New rejection, necessitated by claim amendments: Claims 30, 32, 37 – 39, 41 – 45, and 57 – 58 are rejected under 35 U.S.C. 103 as being unpatentable over MOONEY in view of HARBURY (US 2015/0209753 A1, published 07/30/2015; see PTO-892 submitted with this Office Action).
The present application is directed to a method of making a modified cryogel, comprising: covalently linking a biomolecule to a cryogel, thereby making the modified cryogel; wherein the covalently linking comprises a cycloaddition reaction; and the cryogel comprises a polysaccharide and a co-monomer selected from glycidyl methacrylate and N-(2-hydroxypropyl) methacrylamide (HPMA).
MOONEY is directed to a device comprising (a) a delivery vehicle comprising a scaffold composition, and (b) (i) polyethylenimine (PEI); (ii) free PEI; (iii) PEI and an antigen (biomolecule); or (iv) PEI attached to an antigen [biomolecule]. and that the scaffold composition comprises a hydrogel or a cryogel. See claims 1 and 13. MOONEY teaches that the scaffold composition comprises a polymer or co-polymer of a natural or synthetic polysaccharide. See p. 23, lines 12 – 16.
MOONEY teaches aspects of the present subject matter relate to click-hydrogels and click-cryogels, like click alginate. A click hydrogel or cryogel is a gel in which cross-linking between hydrogel or cryogel polymers is facilitated by click reactions between the polymers. Each polymer may contain one of more functional groups useful in a click reaction. Given the high level of specificity of the functional group pairs in a click reaction, active compounds can be added to the preformed device prior to or contemporaneously with formation of the hydrogel device by click chemistry. Non-limiting examples of click reactions that may be used to form click-hydrogels include Copper I catalyzed azide-alkyne cycloaddition. See paragraph bridging pp. 100-101 and 2nd paragraph on p.101.
HARBURY is directed to monoliths with attached recognition compounds which selectively bind ligands [biomolecules], methods of preparing such monoliths, arrays thereof and uses thereof. See abstract. HARBURY teaches that the monolith is a cryogel monolith (see paragraph 0105) and that cycloaddition of complementary functional groups (e.g., azide and acetylene; diene and electron deficient olefin) or click chemistry may be used to attach the recognition compound to the monolith (see paragraph 0074). Furthermore, HARBURY teaches that “polymer” includes copolymer, that the term “monomer” includes co-monomer, that polymers include polysaccharides (see paragraph 0058), and that glycidyl methacrylate may be used as a monomer (see paragraphs 0036, 0081 and paragraph 0082, fifth structure from top).
Because MOONEY and HARBURY each teach a modified cryogel linked to a biomolecule (such as an antigen or a ligand which HARBURY teaches may be covalently attached via cycloaddition) comprising a polysaccharide and a co-monomer (which HARBURY teaches may be glycidyl methacrylate), it would have been obvious to one having ordinary skill in the art to modify MOONEY’s cryogel by linking the biomolecule via cycloaddition and use a glycidyl methacrylate as a co-monomer as HARBURY teaches to arrive to the invention of present claims 30 and 37. There would have been a reasonable expectation of success considering that modified cryogels are known to be used in biomaterial-based scaffolds as evidenced by the applied prior art.
Regarding claim 32, MOONEY discloses that the scaffold composition comprises a polymer or a copolymer of a natural or synthetic polysaccharide (see p. 23, lines 12 – 16) and that the polymer or copolymer is methacrylated (see p. 23, line 28).
Regarding claims 38 – 39, MOONEY discloses that in an exemplary synthesis process, (i) Alginate (a naturally occurring, biocompatible polysaccharide) is chemically modified to allow radical polymerization, (ii) Methacrylated (MA)-alginate is added to ammonium persulfate (APS)/ tetramethylethylenediamine (TEMED) initiator system before incubation at -20 °C to allow ice crystal formation. See p. 43, lines 14 – 18.
Regarding claims 41 – 42, MOONEY discloses linking via functional groups that may be used in the method of covalently coupling peptides/proteins to polymers. See p. 114, lines 12 – 15 (table). MOONEY’s table on p. 114 discloses the carboxyl linking group ( -COOH, fifth from the top).
Regarding claim 43, according to the present specification, azido-propylamine is an azido-terminal molecule (p. 13, lines). An azido group is an -N3 group or an azide group and is a residue derived from azido-propylamine. MOONEY teaches that a bioorthogonal functional group and the target recognition molecule [biomolecule] comprise a complementary functional group, where the bioorthogonal functional group is capable of chemically reacting with the complementary functional group to form a covalent bond. See p. 117, lines 18 – 20. MOONEY teaches that that biorthogonal functional group may be an azide. See p. 118, table. Thus, it would have been obvious to use a compound such as azido-propylamine to provide an azido functional group as a linking group, thereby arriving to the invention of claim 43.
Regarding claim 44, HARBURY teaches that a “linker” is any molecule or substance which performs the function of linking the monolith to the recognition compound, which can be PEG. See paragraph 40.
Regarding claim 45, MOONEY teaches a bioorthogonal functional group comprises dibenzocyclooctyne (DBCO). See p. 117, lines 27 – 28. Because MOONEY teaches that a bioorthogonal functional group and the target recognition molecule [biomolecule] comprise a complementary functional group, where the bioorthogonal functional group is capable of chemically reacting with the complementary functional group to form a covalent bond and that DBCO is a biorthogonal functional group, it would have been obvious to use a residue of DBCO as the linking group to arrive to the invention of claim 45.
Regarding claim 57, MOONEY teaches that the disclosed device further comprises (a) an immunostimulatory compound; (b) a compound that attracts an immune cell to or into the delivery vehicle; (c) a compound that induces immunogenic cell death of a tumor cell; (d) a compound that inhibits T-cell or dendritic cell suppression; (e) a compound that inhibits an immune-inhibitory protein, or any combination thereof, which may be heparin. See p. 28, lines 1 – 11.
Regarding claim 58, according to the present specification, the cryogels include T cell-activating biomolecules (aCD3/aCD28Ab) (Example 7, p. 18). MOONEY teaches that the cryogel further comprises an immunostimulatory compound, which may be an immunostimulatory antibody. See claim 18 and p. 86, lines 4 – 6. Although MOONEY does not expressly teach that the biomolecule of the present invention is a CD3 or CD28 antibody, because a CD3/CD28 antibody is immunostimulatory, it would have been obvious to modify MOONEY’s cryogel to include a CD3 or CD28 antibody.
Response to Arguments
On page 6, second paragraph, of the reply of 10/01/2025, Applicant argues that “Mooney fails to teach or suggest covalently linking a biomolecule via a cycloaddition reaction to a cryogel, wherein the cryogel comprises a polysaccharide and a co- monomer selected from glycidyl methacrylate and N-(2-hydroxypropyl) methacrylamide (HPMA), as instantly claimed. Accordingly, claims 30-32 and 41, as amended, are not anticipated by Mooney.”
Applicant’s argument has been fully considered but not found persuasive because MOONEY in view of HARBURY renders covalently linking a biomolecule via a cycloaddition reaction to a cryogel, wherein the cryogel comprises a polysaccharide and a co- monomer selected from glycidyl methacrylate obvious as discussed in the 103 rejection above.
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.
Previous rejection, maintained in modified form: claims 30, 32, 37 – 39, 41 – 45, and 57 – 58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 12 of U.S. Patent No. 8,529,897 in view of MOONEY and HARBURY.
Patented claim 1 recites a composition comprising: a hyaluronan matrix; and a monoclonal antibody directly conjugated to the hyaluronan matrix, wherein the antibody is selected from the group consisting of an anti-IL-1β, an anti-TNF-α, and combinations thereof.
The hyaluronan matrix is a polysaccharide matrix and the antibody is a biomolecule and thus reads on the present claims. The main difference between the present claims and the patented claims is that the present claims recite a method of making a making a polysaccharide cryogel with a glycidyl methacrylate co-monomer. However, MOONEY in view of HARBURY discloses this difference. The teachings of MOONEY and HARBURY, and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the patented claims recite a polysaccharide matrix (hyaluronan matrix) connected to a biomolecule (antibody) and MOONEY in view of HARBURY discloses a method of making a modified cryogel with the features of present claim 30, it would have been obvious to one having ordinary skill in the art to use MOONEY and HARBURY’s method in the making the patented-claims’ modified cryogel antibody to arrive to the present claims. There would have been a reasonable expectation of success given a modified cryogel with a biomolecule has been known to be useful as a pharmaceutical delivery vehicle or in assays, as evidenced by the applied prior art.
Response to Arguments
On p. 7, last paragraph, of the reply of 10/01/2025, Applicant argues that “[t]he claims of U.S. Patent No. 8,529,897 are directed to a method for treating wounds with a composition comprising a hyaluronan matrix and a conjugated monoclonal antibody. The claims of U.S. Patent No. 8,529,897 do not overlap with the presently claimed subject matter, which is directed to a method of making a modified cryogel. Therefore, the presently claimed subject matter is patentably distinct from the claims of U.S. Patent No. 8,529,897. ”
Applicant’s argument is not persuasive because the patented claims recite a hyaluronan [polysaccharide] matrix with an antibody [biomolecule] and MOONEY in view of HARBURY renders the claimed method of making the polysaccharide matrix, which may be a cryogel, with the structural limitations of the present claims obvious for the reasons discussed in the 103 rejection above.
Previous rejection, maintained in modified form: claims 30, 32, 37 – 39, 41 – 45, and 57 – 58 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 13 of U.S. Patent No. 11,850,325 in view of MOONEY and HARBURY.
Patented claim 5 recites a cryogel, comprising: a residue of a compound of claim 1; and
a hydrophilic bio-compatible polymer.
Patented claim 6 recites the cryogel of claim 5, wherein the residue of a compound of claim 3 is crosslinked to the hydrophilic bio-compatible polymer.
Patented claim 7 recites the cryogel of claim 5, wherein the hydrophilic bio-compatible polymer is selected from the group consisting of a gelatin-based bio-compatible polymer and a hyaluronic acid-based bio-compatible polymer.
The main difference between the present claims and the patented claims is that the present claims recite a method of making a modified cryogel with a biomolecule with the features of present claim 30. However, MOONEY in view of HARBURY discloses this difference. The teachings of MOONEY and HARBURY, and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the patented claims recite a modified cryogel and MOONEY in view of HARBURY discloses a method of making a modified cryogel with the features of claim 30, it would have been obvious to one having ordinary skill in the art to use MOONEY and HARBURY’s method in the making the patented-claims’ modified cryogel to arrive to the present claims. There would have been a reasonable expectation of success given a modified cryogel with a biomolecule has been known to be useful as a pharmaceutical delivery vehicle or in assays, as evidenced by the applied prior art.
Response to Arguments
On p. 8, second paragraph, of the reply of 10/01/2025, Applicant argues that “[t]he claims of U.S. Patent No. 11,850,325 do not overlap with the presently claimed subject matter, which is directed to a method of making a modified cryogel. Therefore, the presently claimed subject matter is patentably distinct from the claims of U.S. Patent No. 11,850,325.”
Applicant’s argument is not persuasive because the patented claims recite a modified cryogel and MOONEY in view of HARBURY renders the claimed method of making the modified cryogel with the structural limitations of the present claims obvious for the reasons discussed in the 103 rejection above.
Previous rejection, withdrawn: claims 1 – 7, 30 – 35, and 40 – 41 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 36, 59, 70, and 71 of copending Application No. 17/600,198 in view of MOONEY.
In view of the abandonment of Application No. 17/600,198, this rejection is withdrawn.
Conclusion
Claims 30, 32, 37 – 39, 41 – 45, and 57 – 58 are rejected.
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 ESTELLA M. GUSTILO whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:00 AM - 5:00 PM.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/PETER J REDDIG/Primary Examiner, Art Unit 1646
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