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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06 Jan 2026 has been entered.
Response to Amendment
Status of the Claims
Receipt of Applicant’s response, filed 06 Jan 2026 has been entered.
Claims 1-7, 10-18, 21 and 22 remain pending in the application.
Claims 1, 13 and 14, and 22 are amended.
Claims 8, 9, 19 and 20 are cancelled.
Claims 2, 11, and 15 are withdrawn from further consideration by the examiner, pursuant to 37 CFR 1.142(b), as being drawn to a non-elected species.
Claims 1, 3-7, 10, 12-14, 16-18, 21 and 22 are under consideration to the extent that the first reactive group comprises an azide group, the second reactive group comprises an alkyne group, and the species of hydrophilic polymer and crosslinking agent comprise branched polymers.
Objections Withdrawn
Objections to the Claims
The claim objections set forth in the Final Office Action mailed 07 Oct 2025 are hereby withdrawn in light of applicant’s amendments of the claims.
Rejections Withdrawn
Rejections Pursuant to 35 USC § 112
The rejections of the claims pursuant to 35 U.S.C. 112(b) set forth in the Final Office Action mailed 07 Oct 2025 are hereby withdrawn in light of applicant’s amendment of the claims.
The rejections of the claims regarding the “non-hydrogel microbeads” pursuant to 35 U.S.C. 112(a) set forth in the Final Office Action mailed 07 Oct 2025 are hereby withdrawn in light of applicant’s amendment of the claims.
Rejections Pursuant to 35 USC § 103
The rejection of claims 1, 3-7, 10, 12-14, 16-18, 21 and 22 under 35 U.S.C. 103 as being unpatentable over Schwarz et al. (US 2003/0215519, published 20 Nov 2003) in view of Jiang et al. (Soft Matter, 2015, 11, 6029—6036) as evidenced by Agard et al. (J. AM. CHEM. SOC. 2004, 126, 15046-15047) and Yao (US2005/0271727, published 08 Dec 2005) as evidenced by the instant specification is withdrawn in favor of the new grounds of rejection set forth below.
Rejections Maintained
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.
Claims 1, 3-7, 10, 12, 14, 16-18, 21 and 22 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.
The amendment filed 23 Jun 2025 has introduced new matter into the claims. Amended claim 1 recites that the “the embolic hydrogel crosslinks a first portion of the bio-compatible microbeads to other bio-compatible microbeads or crosslinks portions of the embolization coil with other portions of the embolization coil to form a hydrogel incorporating microbeads or an embolization coil.” Amended claim 14 recites that the “the embolic hydrogel crosslinks a first portion of the bio-compatible microbeads to a second portion of the bio-compatible microbeads so as to form a hydrogel incorporating microbeads.” The response filed 23 Jun 2025 indicates that support for amended claim 1 can be found at pages 7, 9, 11 and 12 of the specification. This has been fully considered but is not found persuasive. The originally filed disclosure does not disclose that only a portion of the microbeads or embolization coil are embolized with other microbeads or other portions of the coil. Instant claims 1 and 14 now recite limitations, which were not clearly disclosed in the specification as filed, and now change the scope of the instant disclosure as filed. Such limitations recited in newly amended claim 1 and 14, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C 112. Applicant is required to provide sufficient written support for the limitations recited in present claim 1 and 14 in the specification or claims, as-filed, or remove these limitations from the claims in response to this Office Action.
Response to Arguments
Applicant's arguments filed 06 Jan 2026 have been fully considered. The examiner notes that the applicant did not address the 112(a) rejection for new matter regarding the limitation of a embolizing a portion of microbeads as detailed above.
New Grounds of Rejection
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.
Claim 1, 3-7, 10, 12, 14, 16-18, 21 and 22 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.
The amendment filed 23 Jun 2025 has introduced new matter into the claims. Claims 1 and 14 recite the “bio-compatible microbeads.” The response filed 23 Jun 2025 indicates that support for amended claim 1 can be found at pages 7, 9, 11 and 12 of the specification. This has been fully considered but is not found persuasive. The originally filed disclosure does not disclose bio-compatible microbeads. Instant claims 1 and 14 now recite limitations, which were not clearly disclosed in the specification as filed, and now change the scope of the instant disclosure as filed. Such limitations recited in newly amended claim 1 and 14, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C 112. Applicant is required to provide sufficient written support for the limitations recited in present claim 1 and 14 in the specification or claims, as-filed, or remove these limitations from the claims in response to this Office Action.
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.
Claim 1, 3-7, 10, 12, 14, 16-18, 21 and 22 is rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al. (Soft Matter, 2015, 11, 6029—6036) in view of Yao (US2005/0271727, published 08 Dec 2005), Reb (WO 2017/143277, published 24 Aug 2017) and Madani et al. (Biomaterials 28 (2007) 1198–1208).
Jiang teaches an injectable and fast-degradable poly(ethylene glycol) hydrogel fabricated via bioorthogonal strain-promoted azide-alkyne cycloaddition click chemistry (title, abstract). Jiang teaches that poly(ethylene glycol) (PEG) is widely used in the biomedical field because of its good biocompatibility and hydrophlicity and that PEG-based hydrogels cross-linked by a biorthogonal SPAAC click reaction would be very promising for biomedical uses (page 6030 col 1 lines 22-27). Jiang teaches the hydrogels may be useful as biomaterials such as embolic agents for intraventional therapy (abstract, page 6030 col. 2 lines 1-3). Jiang teaches an example where PEG was attached to an azide group (2,2-bis(azidomethyl) propane-1,3-diol) and PEG was attached to an alkyne group (monofluoro-substituted cyclooctyne) and the two PEG groups were reacted to form a hydrogel (see page 6031 col. 1, Figure 1, Scheme 1), thereby rendering obvious the active groups of the embolic hydrogel of the instant claims. Jiang teaches that the hydrogel is biodegradable and that the fast-degradable injectable PEG-based hydrogel is promising for use as a temporary embolic agent (page 6030 lower left and top right).
Jiang teaches that the hydrogel was formed by simply mixing the azide and cyclooctyne modified PEGs (page 6033 Formation and characterization of the hydrogel) and the two gel precursors were injected and the hydrogel formed in vivo (page 6032 left column first paragraph, page 6034 left column) rendering obvious the administration of the reactive groups separately and their binding in vivo to form the hydrogel. Regarding the limitation of a strained alkyne of claims 5 and 17, Jiang teaches that to avoid the toxicity of exogenous metal catalysts, the cross-linking process is based on the inherent ring strain of monofluoro-substituted cyclooctyne (MFCO), which could effectively trigger the click reaction with azide groups on the PEG chains (page 6032 Design of the hydrogel). Regarding the limitation of the formation of a tri-azole ring upon reacting of claims 7 and 18, as evidenced by Agard, the strain promoted reaction of the azide group and the cyclooctyne group would necessarily form a tri-azole ring upon reacting (see Figure 1(B)). Regarding the limitation of a covalent bond between the reactive groups as recited in claim 6, it is noted that the reaction of the azide and the cyclooctyne groups would necessarily form covalent bonds. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). Regarding the limitation “at least two reactive groups” as recited in claim 12, Jiang teaches that the polymer of the invention may comprise multiple reactive groups. See Figure 1 where the PEG polymers comprise multiple cyclooctyne groups and multiple azide groups. Regarding claims 21 and 22, Jiang varied the precursor concentration and teaches that the ratio of the PEG-azide and PEG-MFCO groups were varied from 1:1.5 to 1:5 and that ratios too low or too high led to failure in hydrogel formation (page 6033 left column, Table 1). Thus, it is obvious that the hydrogel will form when the concentrations are high enough to form a crosslinked network and that one group may be in excess to the other group administered.
Jiang does not teach the use of a branched polymer (the elected species of polymer) or retaining the polymer on microbeads. These deficiencies are made up for in the teachings of Yao, Reb and Madani.
Yao teaches polymeric biocompatible hydrogels based on the mixtures of poly(vinyl alcohol) (PVA) and poly(ethylene glycol) (PEG) macromers (abstract, [0021]). Yao teaches that the hydrogels may be used for embolic therapies (abstract). Yao teaches that the PEG or PVA hydrogels may be formed by crosslinking the PEG or PVA polymers using crosslinking groups that form a biodegradable covalent bond ([0030]-[0035]). Yao teaches that any of the forms of the hydrophilic PEG are suitable for forming the hydrogels, including branched PEG ([0069], [0074]).
Reb teaches microspheres containing therapeutic agents that may be used for therapeutic embolization ([0002], [0003]). Reb teaches that the microsphere may comprise a biocompatible polymeric material ([0025]-[0027]). Reb teaches an embodiment where the microsphere may include an alkyne functional group that reacts with an azide-containing cyclodextrin derivative via click chemistry to form a triazole adduct ([0073]).
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Reb teaches that the microspheres may be biodegradable ([0062]) and the composition may be in the form of a hydrogel ([0081]), may be injected ([0088]) and may be used for treating tumors and/or other cancers ([0085]). Reb teaches that the microspheres may be used in passive or active embolization therapies, which include using the microspheres to occlude or block a vessel such as a blood vessel ([0086]).
Madani teaches PEGylation of microspheres for therapeutic embolization (title). Madani teaches that the microspheres were spherical semi-rigid microbeads (page 1199 2.1 Preparation and purification of microspheres). Madani teaches that there are several methods for adding PEG or PEG containing copolymers to the surface of micro or nano particles and that the PEGylation of therapeutic particles is a widely used method to mask or camouflage particles from the mononuclear phagocytic system. The hydrophilic protective PEG layer around the particles is able to inhibit the adsorption of opsonin proteins via steric repulsion forces, thereby blocking and delaying the first step in the phagocytic process and resulting in an increase in blood circulation half-life of the particles by several orders of magnitude (page 1199 col 1 lines 9-21). Madani teaches that the PEG layer on the microspheres should reduce inflammation and improve the biocompatibility of the material for embolization (page 1199 col 1 lines 22-35).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have substituted the hydrophilic PEG in the hydrogel as taught by Jiang with a branched PEG as taught by Yao and to have coupled either the PEG-azide or PEG-alkyne polymer made obvious by Jiang with microspheres and to form a hydrogel in vivo, linking the microspheres together for purposes of embolization. Branched PEG is a suitable hydrophilic polymer for forming embolic hydrogels as taught by Yao. Thus, one of ordinary skill would have a reasonable expectation of successfully forming an embolic hydrogel via an azide-alkyne click chemistry reaction using branched PEG as this merely represents a simple substitution of one known element for another for use in a similar purpose, namely as an embolic hydrogel. Microspheres are known for embolization therapies as taught by Reb and Madani and polymers may be attached to microspheres and undergo click chemistry azide-alkyne reactions as taught by Reb. Similar azide-alkyne hydrogels are taught by Jiang and it would be obvious to combine the hydrogel components taught by Jiang with a microsphere as taught by Reb for the beneficial embolization properties of the microsphere and as an alternative to the embolic hydrogel alone taught by Jiang. Microspheres for embolization may have increased biocompatibility with decreased inflammation through PEG coatings on the microspheres as taught by Madani. Thus, one of ordinary skill in the art would have a reasonable expectation of successfully utilizing microspheres for improved embolic therapies by coating with the PEG-azide/alkyne which may then undergo the click chemistry hydrogel formation.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Response to Arguments
Applicant's arguments filed 06 Jan 2026 have been fully considered. The examiner notes that the previous rejection utilizing the teachings of Schwarz has been withdrawn in favor the rejection detailed above. Regarding the teachings of Jiang and Yao, the applicant argues that there is no teaching in Jiang or Yao of crosslinking microbeads or embolic coils and retaining the reactive groups on the bead/coil. The examiner notes that this deficienciy is made up for in the teachings of Reb where reactive groups are attached to embolic microspheres. As detailed above, the combined teachings of Jiang, Yao, Reb and Madani render obvious the attachment of polymers with the specific azide/alkyne hydrogel forming reactive groups to microspheres and the formation of the hydrogel in vivo.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EDWIN C MITCHELL whose telephone number is (571)272-7007. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/E.C.M./Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600