DETAILED ACTION-
An Office Action was mailed 10/16/2025. Applicant filed a Response, amended claims 1-2 and 4-5, and added claims 6-14 on 04/09/2026.
Claims 1-2 and 4-14 are pending.
Claims 1-2, 4-12 and 14 are rejected.
Claim 13 is withdrawn from consideration.
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
Newly submitted claim 13 is directed to an invention that lacks unity with the invention originally claimed for the following reasons:
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), an international application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in an international application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Processes, Products, and/or Apparatuses:
Products, processes of manufacture, processes of use, and apparatuses are different categories of invention. When an application includes claims to more than one product, process, or apparatus, the first invention of the category first mentioned in the claims of the application and the first recited invention of each of the other categories related thereto will be considered as the “main invention” in the claims. In the case of non-compliance with unity of invention and where no additional fees are timely paid, the international search and/or international preliminary examination, as appropriate, will be based on the main invention in the claims. See PCT Article 17(3)(a), 37 CFR 1.475(d), 37 CFR 1.476(c) and 37 CFR 1.488(b)(3).
As provided in 37 CFR 1.475(b), an international application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475(c).
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
Group I, claims 1-2, 4-12 and 14, drawn to a composition.
Group II, claim 13, drawn to a method.
Groups I and II lack unity of invention because even though the inventions of these groups require the technical feature of a photo-melting composition, comprising: a cross-linked body of a hydrophilic polymer comprising a cross-linkable functional group, wherein the hydrophilic polymer comprises carboxymethyl cellulose; and a photo-radical generating agent, wherein the cross-linked body is a hydrophilic polymer cross-linked through a disulfide bond, and wherein the photo-melting composition is configured to melt by irradiation with light, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Carlson et al, US 2013/0142763 A1 (Carlson).
Carlson teaches a crosslinked cellulosic polymer that is the product of a reaction between one or more cellulosic polymers and a crosslinking agent, wherein cellulosic polymers include hydroxyethyl cellulose (HEC) and carboxymethyl cellulose (CMC), i.e., a hydrophilic polymer comprising a cross-linkable functional group, wherein the hydrophilic polymer may be carboxymethyl cellulose (Carlson; [0002] and [0038]). The crosslinking agent may be provided with reactable functional groups, and include thiodiacids and disulfides (Carlson; [0002] and [0017]).
Fig. 2 shows the formation of a crosslinked cellulosic polymer crosslinked through a disulfide bond as claimed (Carlson; Fig. 2 and [0123]):
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Carlson discloses that the composition may further include a photo-initiator (i.e., a photo-radical generating agent), wherein initiators include phenones and hydrogen peroxide (a photo-radical generating agent with water solubility of claim 7) (Carlson; [0077]).
Example 1 demonstrates the Synthesis of 3-(2-carboxy-ethyldisulfanyl)-propionic acid (CSP) crosslinked HEC hydrogel (Fig. 3) (Carlson; Fig 3 and [0125]). Natrosol LR 250 Pharm, which is pharmaceutical grade HEC, is reacted in the presence of 1-ethyl-3-(3-dimethylamino)propylcarbodiimide (EDC) to form a crosslinked hydrogel (Carlson; Fig. 3 and [0124-0126]).
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Example 2 demonstrates the Synthesis of the Functionalized, Crosslinkable HEC of Fig 4. Natrosol LR 250 Pharm (i.e., HEC ) is reacted in the presence of EDC and then CSP is added (Carlson; Fig. 4 and [0127]). As explained in above, CSP is a condensation agent (instant spec at ¶ [0036]). CSP conjugated HEC was treated with dithiothreitol (DTT) to form thio-functionalized HEC (HEC-SH) (Carlson; Fig. 4 and [0127]).
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To form a crosslinked hydrogel of HEC-SC, a small amount of hydrogen peroxide can be added to catalyze the reaction (Carlson; [0128]). Carlson teaches that the composition may further include a photo-initiator (i.e., a photo-radical generating agent), wherein initiators include hydrogen peroxide (Carlson; [0077]).
Although Carlson exemplifies using the cellulose polymer HEC, it would have been obvious to one of ordinary skill in the art to substitute the exemplified HEC with CMC as claimed (i.e., the hydrophilic polymer carboxymethyl cellulose comprising a carboxy crosslinkable functional group as claimed) because Carlson teaches the equivalence between using HEC and CMC as the cellulose polymer to form the cross-linked polymers, and thereby arrive at the claimed invention.
In addition to teaching that the compositions may comprise photoinitiators (Carlson; [0077]), Carlson teaches that cellulosic polymer molecules are linked to coupling agents that are capable of coupling together for crosslinking cellulosic polymer molecules either intermolecularly or intramolecularly. Some crosslinkable coupling agents permit reversible crosslinking, such as crosslinkers that include disulfide groups that can be broken into separate thiol groups, i.e., crosslinking agents that are capable of forming disulfide linkages are both crosslinkable and reversible (i.e., meltable). Thiol coupling agents may also be crosslinking agents as they can form crosslinkers having disulfides (Carlson; [0044]).
The instant specification teaches the term “melting” means that the disulfide bond is (cut by light irridation), and the molecular weight of the compound having the disulfide bond is lowered so that the composition is melted (paragraph [0052] of the specification). Therefore, Carlson’s teaching of reversible disulfide linkages is equivalent to the claimed “melting”.
Although Carlson does not explicitly disclose that the crosslinked polymer compositions and hydrogels are photo-melting as presently claimed (emphasis added), given that the crosslinked polymer compositions of Carlson are substantially identical to the claimed compositions in that they comprise the claimed carboxymethyl cellulose crosslinked through disulfide bonds and a photoinitiator (photo-radical generating agent), wherein crosslinking is reversible, it is clear that the crosslinked polymer compositions of Carlson would inherently be “photo-melting” and configured to melt by irradiation with light as presently claimed.
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 either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). See MPEP 2112.01 (I).
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, Group II, claim 13 is withdrawn from consideration as being directed to a nonelected invention. See 37 CFR 1.142(b) and MPEP § 821.03. To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
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 1-2 and 4-12 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 1 has been amended to recite that the hydrophilic polymer “comprises carboxymethyl cellulose.” This claim language suggests that the cross-linked body may comprise a hydrophilic polymer other than carboxymethyl cellulose. However, the specification as originally filed does not appear to provides basis for cross-linked bodies comprising more than one kind of hydrophilic polymer.
Applicant points to paragraph [0008] of the specification and original claim 3 for basis for this claim amendment. Paragraphs [0008] and [0024] state “The hydrophilic polymer (for example) may be carboxymethyl cellulose.” Original claim 3 claimed “wherein the hydrophilic polymer is carboxymethyl cellulose.”
Throughout the specification, the terms “a” and “the” (singular) are used to define the crosslinked body and the hydrophilic polymer (paragraphs [0002], [0004-0006], [0009-0011], [0017-0024], [0033-0034], [0052]). Mixtures thereof are never taught or suggested, i.e., that the hydrophilic polymer may comprise carboxymethyl cellulose and an additional hydrophilic polymer. All of the examples use a single polymer, i.e., CMC (paragraphs 0058-0077]).
Original claim 1 recited “a composition comprising a cross-linked body of a hydrophilic polymer.”
Amending claim 1 to read “wherein the hydrophilic polymer is carboxymethyl cellulose” can overcome this rejection.
Regarding dependent claims 2 and 4-13, these claims do not remedy the deficiencies of parent claim 1 noted above, and are rejected for the same rationale.
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.
Claim 2 is 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 2 is indefinite with regard to the term “at least one type.” The addition of the word "type" to an otherwise definite expression (e.g., Friedel-Crafts catalyst) extends the scope of the expression so as to render it indefinite. Ex parte Copenhaver, 109 USPQ 118 (Bd. Pat. App. & Inter. 1955). Likewise, the phrase "ZSM-5-type aluminosilicate zeolites" was held to be indefinite because it was unclear what "type" was intended to convey. Ex parte Attig, 7 USPQ2d 1092 (Bd. Pat. App. & Inter. 1986). See MPEP 2173.05(b).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2 and 5 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 recites “wherein the cross-linkable functional group comprises at least one type of group selected from the group consisting of a carboxy group and an amino group.” Claim 1, from which claim 2 depends, recites that the hydrophilic polymer comprising a cross-linkable functional group comprises carboxymethyl cellulose, i.e., a hydrophilic polymer having a carboxy group. Carboxymethyl cellulose does not have an amino group. Hydrophilic polymers wherein the cross-linkable functional group comprises at least one type of a carboxy group is broader in scope than carboxymethyl cellulose. Therefore claim 2 is broader in scope than claim 1 from which it depends.
Although the specification teaches that the hydrophilic polymers may have at least one of a carboxyl group and/or an amino group at paragraph [0018], the specification does not appear to teach that mixtures of hydrophilic polymers may be used (see pages 5-7 above).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 5 recites “wherein the cross-linked body is a condensation reaction product of a hydrophilic polymer comprising a carboxy group and a reactive compound comprising a disulfide bond and an amino group, or a condensation reaction product of a hydrophilic polymer comprising an amino group and a reactive compound comprising a disulfide bond and a carboxy group” (emphasis added).
Claim 1, from which claim 5 depends, recites that the hydrophilic polymer comprising a cross-linkable functional group comprises carboxymethyl cellulose, i.e., a hydrophilic polymer having a carboxy group. Carboxymethyl cellulose does not have an amino group. Further, “a hydrophilic polymer comprising a carboxy group” is broader in scope than carboxymethyl cellulose. Therefore, claim 5 is broader in scope than claim 1 from which it depends.
Examiner notes the specification does not appear to teach that mixtures of hydrophilic polymers may be used (see pages 5-7 above).
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.
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.
Claims 1-2, 4, 7, 10, 12 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Carlson et al, US 2013/0142763 A1 (Carlson).
Regarding claims 1-2, 4, 7, 10 and 14, Carlson teaches a crosslinked cellulosic polymer that is the product of a reaction between one or more cellulosic polymers and a crosslinking agent, wherein cellulosic polymers include hydroxyethyl cellulose (HEC) and carboxymethyl cellulose (CMC), i.e., a hydrophilic polymer comprising a cross-linkable functional group, wherein the hydrophilic polymer may be carboxymethyl cellulose (Carlson; [0002] and [0038]). The crosslinking agent may be provided with reactable functional groups, and include thiodiacids and disulfides (Carlson; [0002] and [0017]).
Fig. 2 shows the formation of a crosslinked cellulosic polymer crosslinked through a disulfide bond as claimed (Carlson; Fig. 2 and [0123]):
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Carlson discloses that the composition may further include a photo-initiator (i.e., a photo-radical generating agent), wherein initiators include phenones and hydrogen peroxide (a photo-radical generating agent with water solubility of claim 7) (Carlson; [0077]).
Example 1 demonstrates the Synthesis of 3-(2-carboxy-ethyldisulfanyl)-propionic acid (CSP) crosslinked HEC hydrogel (Fig. 3) (Carlson; Fig 3 and [0125]). Natrosol LR 250 Pharm, which is pharmaceutical grade HEC, is reacted in the presence of 1-ethyl-3-(3-dimethylamino)propylcarbodiimide (EDC) to form a crosslinked hydrogel (Carlson; Fig. 3 and [0124-0126]).
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The instant specification at ¶ [0036] teaches that EDC is a condensation agent. Therefore, Carlson teaches wherein the cross-linked body is a condensation reaction product of the hydrophilic polymer (HEC) and a reactive compound comprising a disulfide bond and a reactive group capable of forming a bond by a reaction with the cross-linkable functional group (CSP) as claimed (claim 4), for form a hydrogel composition (claim 10).
Example 2 demonstrates the Synthesis of the Functionalized, Crosslinkable HEC of Fig 4. Natrosol LR 250 Pharm (i.e., HEC ) is reacted in the presence of EDC and then CSP is added (Carlson; Fig. 4 and [0127]). As explained in above, CSP is a condensation agent (instant spec at ¶ [0036]). CSP conjugated HEC was treated with dithiothreitol (DTT) to form thio-functionalized HEC (HEC-SH) (Carlson; Fig. 4 and [0127]). HEC-SH has a carboxy cross-linkable functional group as claimed (claim 2).
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To form a crosslinked hydrogel of HEC-SC (i.e., the hydrogel of claim 10), a small amount of hydrogen peroxide can be added to catalyze the reaction (Carlson; [0128]). Carlson teaches that the composition may further include a photo-initiator (i.e., a photo-radical generating agent), wherein initiators include hydrogen peroxide (Carlson; [0077]). Carlson, therefore, teaches a composition comprising: HEC-SH (i.e., a cross-linked body of a hydrophilic polymer) comprising a carboxy group (i.e., the cross-linkable functional group of claim 2); and hydrogen peroxide (i.e., a photo-radical generating agent), wherein the cross-linked body is a crosslinked hydrogel (claim 10) based on HEC (i.e., a hydrophilic polymer cross-linked through a disulfide bond) (claim 1).
Although Carlson exemplifies using the cellulose polymer HEC, it would have been obvious to one of ordinary skill in the art to substitute the exemplified HEC with CMC as claimed (i.e., the hydrophilic polymer carboxymethyl cellulose comprising a carboxy crosslinkable functional group as claimed) because Carlson teaches the equivalence between using HEC and CMC as the cellulose polymer to form the cross-linked polymers, and thereby arrive at the claimed invention.
In addition to teaching that the compositions may comprise photoinitiators (Carlson; [0077]), Carlson teaches that cellulosic polymer molecules are linked to coupling agents that are capable of coupling together for crosslinking cellulosic polymer molecules either intermolecularly or intramolecularly. Some crosslinkable coupling agents permit reversible crosslinking, such as crosslinkers that include disulfide groups that can be broken into separate thiol groups, i.e., crosslinking agents that are capable of forming disulfide linkages are both crosslinkable and reversible (i.e., meltable). Thiol coupling agents may also be crosslinking agents as they can form crosslinkers having disulfides (Carlson; [0044]).
The instant specification teaches the term “melting” means that the disulfide bond is (cut by light irridation), and the molecular weight of the compound having the disulfide bond is lowered so that the composition is melted (paragraph [0052] of the specification). Therefore, Carlson’s teaching of reversible disulfide linkages is equivalent to the claimed “melting”.
Although Carlson does not explicitly disclose that the crosslinked polymer compositions and hydrogels are photo-melting as presently claimed (emphasis added), given that the crosslinked polymer compositions of Carlson are substantially identical to the claimed compositions in that they comprise the claimed carboxymethyl cellulose crosslinked through disulfide bonds and a photoinitiator (photo-radical generating agent), wherein crosslinking is reversible, it is clear that the crosslinked polymer compositions of Carlson would inherently be “photo-melting” and configured to melt by irradiation with light as presently claimed.
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 either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). See MPEP 2112.01 (I).
Regarding claim 12, Carlson is relied upon as teaching the limitations of claim 1 as discussed above. Carlson teaches that the crosslinked cellulose polymers may be a cell growth scaffold, or may be a hydrogel with pores sufficient for culturing one or more cells (i.e., a scaffold material for a cell culture) (Carlson; [0005] and [0042]).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Carlson as applied to claim 1 above, and further in view of Leichner et al, “Thiolated polymers: Bioinspired polymers utilizing one of the most important bridging structures in nature” (Leichner).
Regarding claim 5, Carlson is relied upon as teaching the limitations of claim 1 as discussed above, specifically hydrogels comprising a cross-linked body of carboxymethyl cellulose through disulfide bonds using a coupling agent, wherein the coupling agent may be disulfide (Carlson; [0002]). The crosslinked cellulose polymers may be a cell growth scaffold, or may be a hydrogel with pores sufficient for culturing one or more cells (Carlson; [0005] and [0042]).
Carlson does not explicitly teach wherein the reactive compound comprises a disulfide bond and an amino group as claimed.
With respect to the difference, Leichner teaches in the life science arena, thiolated polymers have attracted and inspired researchers from different disciplines by their versatile features (Leichner; page 192, para 1). Their capability to form disulfide bonds, the likely most versatile bridging structure in nature, with their own polymer chains through a crosslinking process render them unique among advanced materials (Leichner; page 192, para 2). Such advanced materials include, e.g., scaffolds for tissue engineering and injectable tissue-regenerative hydrogels (Leichner; page 192, para 3).
In Table 4 Leichner presents an “Overview of different types of thiomers, wherein XL=crosslinking (Leichner; page 202, lines 1-2). Leichner teaches that thiolation of carboxymethyl cellulose can be obtained by crosslinking with cysteine (i.e., a reactive compound comprises a disulfide bond and an amino group).
Leichner is analogous art as it teaches a cross-linked body of carboxymethyl cellulose and cysteine, i.e., a reactive compound comprises a disulfide bond and an amino group as claimed.
In light the teachings of Leichner that carboxymethyl cellulose can be thiolated with cysteine, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use cysteine as the crosslinking agent for the carboxymethyl cellulose polymers of Carlson in order to obtain a thiolated crosslinked carboxymethyl cellulose polymer with possible diverse applications such as scaffolds for tissue engineering and injectable tissue-regenerative hydrogels, and thereby arrive at the claimed invention.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Carlson as applied to claim 1 above, and further in view of Wang et al, “Redox-responsive blend hydrogel films based on carboxymethyl cellulose/chitosan microspheres as dual delivery carrier” (Wang).
Wang was cited in the IDS filed 06/27/2023.
Regarding claim 6, Carlson is relied upon as teaching the limitations of claim 1 as discussed above, specifically hydrogels comprising a cross-linked body of carboxymethyl cellulose through disulfide bonds using a coupling agent having thiol groups, wherein the disulfide bonds are reversible (Carlson; [0038] and [0044]). The crosslinked cellulose polymers may be a cell growth scaffold, or may be a hydrogel with pores sufficient for culturing one or more cells (Carlson; [0005] and [0042]).
Carlson does not explicitly teach wherein the cross-linked body is a condensation product carboxymethyl cellulose and cystamine or salts thereof claimed.
With respect to the difference, Wang teaches responsive hydrogels are attractive because of their adaptability, the structure being changeable to environmental stimuli such as oxidative conditions and light. Applications include drug delivery, tissue engineering, and cell scaffolding materials (Wang; page 413, para 1). Carboxymethyl cellulose (CMC) is an important polysaccharide owing to properties like water-solubility, biodegradability, nontoxicity, biocompatibility, high viscosity, and good film forming ability. Recently there are also reports about reduction sensitive cellulose hydrogels as drug delivery systems, and wherein the cross-linked disulfide bonds could be cleaved to rapid release drugs in the presence of redox triggers (Wang; page 413, para 2).
Wang teaches that such hydrogels can be formed by crosslinking carboxymethyl cellulose with cystamine in the presence of 1-(3-Dimethylaminopropyl)-3- ethylcarbodiimide hydrochloride and N-Hydroxysuccinimide (condensation agents and aids as disclosed in para [0036-0038] of Applicant’s specification) (i.e., wherein the crosslinked body is a condensation reaction product of carboxymethyl cellulose with cystamine) (Wang; page 414, para 2.1 “Materials” and para 2.3 “Preparation of 5-FU/CMC/THCS composite hydrogel films’).
The disulfide bond formed is reversible (i.e., meltable):
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(Wang; page 417).
Wang is analogous art as it teaches a cross-linked body that is a condensation product carboxymethyl cellulose and cystamine as claimed.
In light the teachings of Wang that carboxymethyl cellulose can be crosslinked with cystamine in order to form a crosslinked polymer with cleavable disulfide bonds, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use cystamine as the crosslinking agent for the carboxymethyl cellulose polymers of Carlson in order to obtain a crosslinked carboxymethyl cellulose polymer with cleavable disulfide bonds, thus having possible beneficial uses for drug delivery or cell scaffolding, and thereby arrive at the claimed invention.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Carlson as applied to claim 1 above, and further in view of Zeitels et al, US 2010/0055184A1 (Zeitels) taken in view of evidence by Advanced Biomatrix, Safety Data Sheet for Igracure 2959 (Adv BioMatrix).
Regarding claims 8-9, Carlson is relied upon as teaching the limitations of claim 1 as discussed above, wherein crosslinked cellulose polymer hydrogels may be used for cell growth scaffold (Carlson; [0004-0005]). Photoinitiators/catalysts may be used such as hydrogen peroxide and benzophenone (Carlson; [0077]).
Carlson does not explicitly teach the specific photoinitiators of claims 8 and 9, such as 2-Hydroxy-2-Methyl-1-Phenyl Propanone or 2-Hydroxy-4'-(2-Hydroxyethoxy)-2-Methyl Propiophenone).
With respect to the difference, Zeitels teaches hydrogels which may be used to provide a scaffold to introduce cells or other biologically active agents. In certain embodiments, the hydrogen may comprise a cross-linkable derivative of methyl cellulose (Zeitels; [0005]).
The polymer may be crosslinked using a photoinitiator, wherein photoinitiators include, e.g., hydrogen peroxide or benzophenone as taught by Carlson, or 2-hydroxy-2-methyl-1-phenyl-propanone as claimed. In certain embodiments, the photoinitiator is Igracure 2959 (Zeitels; [0052]).
As is evidenced by Adv BioMatrix, Igracure 2959 is 2-Hydroxy-4'-(2-Hydroxyethoxy)-2-Methyl Propiophenone) as claimed in claims 8 and 9 (Adv BioMatrix, “Section 3”).
Zeitels is analogous art as it teaches crosslinked methyl cellulose polymer hydrogels may be used as a scaffold to introduce cells, wherein photoinitiators such as 2-Hydroxy-4'-(2-Hydroxyethoxy)-2-Methyl Propiophenone) may be used for crosslinking.
In light of the disclosure of Zeitels of the equivalence and interchangeability of using photoinitiators such as hydrogen peroxide and benzophenone as disclosed in Carlson, with using 2-hydroxy-2-methyl-1-phenyl-propanone or 2-Hydroxy-4'-(2-Hydroxyethoxy)-2-Methyl Propiophenone (Igracure 2959) as presently claimed, with Igracure 2959 being a preferred embodiment , it would therefore have been obvious to one of ordinary skill in the art to use as presently claimed using 2-hydroxy-2-methyl-1-phenyl-propanone or 2-Hydroxy-4'-(2-Hydroxyethoxy)-2-Methyl Propiophenone as the photoinitiator in Carlson, in order to provide a crosslinked polymer hydrogel for use as a scaffold material for cell culture, and thereby arrive claimed invention.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Carlson as applied to claim 1 above, and further in view Zainal et al, “Preparation of cellulose-based hydrogel: a review” (Zainal).
Regarding claim 11, Carlson is relied upon as teaching the limitations of claim 1 as discussed above, specifically hydrogels comprising a cross-linked body of a cellulosic polymer through disulfide bonds using a coupling agent (Carlson; [0002]). The crosslinked cellulose polymers may be a tissue growth scaffold, or may be a hydrogel with pores sufficient for culturing one or more cells (Carlson; [0005], [0021] and [0042]). The cellulosic polymer may be, e.g., carboxymethyl cellulose (Carlson; [0002] and [0013]).
The hydrogels including the crosslinked cellulose polymer can include water and a buffering agent (Carlson; [0082]). Carlson exemplifies dissolving a crosslinked cellulose polymer in the buffer solution phosphate buffer saline (Carlson; [0125] and [0127]).
Carlson does not teach wherein the composition further comprises sodium hydroxide as claimed.
With respect to the difference, Zainal teaches that carboxymethyl cellulose (CMC) is a water-soluble cellulose derivative used in the biopolymer industry. CMC has properties of biocompatibility, solubility, and biodegradability. CMC-based hydrogels have potential uses in, e.g., wound-healing. CMC also has been used as a crosslinking agent, and it shows the improvement of toughness and self-healing. Since CMC can be diluted in water, the degree of substitution of CMC increases as NaOH concentration increases, improving the ability of CMC dissolution in water (Zainal; pages 941-942, “4.3 Carboxymethyl cellulose”).
Zainal teaches that CMC-based hydrogels result in a materials suitable for self-healing applications and also can be used as sealants and stomach mucosa renovation (Zainal; page 942, Section “5. Preparation of hydrogel,” paragraph 2).
Zainal is analogous art as it teaches CMC can be crosslinked for self-healing (i.e., cell growth), and teaches the dissolution of CMC in water and sodium hydroxide.
In light of the motivation provided by Zainal to use sodium hydroxide to improve the dissolution of CMC in water, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add sodium hydroxide to the aqueous, crosslinked CMC-based hydrogels of Carlson in order to improve the ability of the CMC polymer to dissolve in water for hydrogel formation, and thereby arrive at the claimed invention.
Response to Arguments
1) Examiner acknowledges Applicant’s Amendment to the title. The objection to the specification has been withdrawn.
2) Applicant’s arguments, see Remarks with Amendments filed 04/09/2026, with respect to the 35 U.S.C. §102(a)(1) rejection over Wu et al, "Photoconfigurable, Cell-Remodelable Disulfide Cross-linked Hyaluronic Acid Hydrogels," have been fully considered and are persuasive. The rejection has been withdrawn.
Specifically, Wu does not disclose crosslinked bodies of a hydrophilic polymer, wherein the hydrophilic polymer comprises carboxymethyl cellulose as presently claimed.
3) Applicant’s arguments, see Remarks with Amendments filed 04/09/2026, with respect to the 35 U.S.C. §102(a)(1) rejection over Carlson et al, US 2013/1042763A1 (Carlson) have been fully considered and are persuasive. The 35 USC 102 rejection has been withdrawn.
Specifically, Carlson does not anticipate crosslinked bodies of a hydrophilic polymer, wherein the hydrophilic polymer comprises carboxymethyl cellulose as presently claimed.
4) Regarding the 35 U.S.C. §103 rejection over Carlson, Applicant’s Remarks and Amendments filed 04/09/2026 have been fully considered, but are not deemed persuasive for the following reasons.
Applicant primarily argues:
“Carlson discloses that the composition may further include a photo-initiator (i.e., a photo-radical generating agent), wherein initiators include phenones and hydrogen peroxide (Carlson; [0077]).
However, the phenone and hydrogen peroxide described in Carlson are crosslinking initiators used for crosslinking cellulose polymers; that is, the phenone and hydrogen peroxide are used to form the crosslinked cellulose polymers. There is no disclosure that would suggest that, after formation of the crosslinked cellulose polymers, there is a composition comprising both the crosslinked cellulose polymers and phenone and/or hydrogen peroxide.”
Remarks, page 9.
Examiner respectfully disagrees for the following reasons. See, for example, Example 2 of Carlson wherein Natrosol LR 250 Pharm (i.e., HEC ) is mixed with EDC and CSP (condensation agent). CSP conjugated HEC was then treated with dithiothreitol (DTT) to form thio-functionalized HEC (HEC-SH) (Carlson; Fig. 4 and [0127]). To form a crosslinked hydrogel, a small amount of hydrogen peroxide is used to catalyze the reaction (Carlson; [0128]). As a catalyst, the hydrogen peroxide speeds up the reaction rather than being consumed by the reaction. There is no teaching or suggestion by Carlson that the hydrogen peroxide photo-initiator in fully consumed. Further, the claims do not require any specific amount of photo-radical generating agent.
The examples in the specification appear to comprise process steps similar to those of Carlson. The preparation method includes dissolving a condensation agent, reaction aid and hydrophilic polymer in an aqueous solution. Simultaneously, an aqueous solution of a photo-radical generating agent and reactive compound is prepared, followed by mixing the two solutions (specification at paragraph 0062]). The method does not require or recite that the photo-radical generating agent is added to a preformed, cross-linked body.
Therefore, Examiner maintains that the compositions of Carlson comprise a crosslinked body and photo-radical generating agent as presently claimed.
5) Applicant further argues:
“Moreover, there is no teaching or suggestion in Carlson et al. of a photo-melting composition that is configured to melt by irradiation with light, as recited in amended claim 1 and new claim 14.”
Remarks, page 9.
Although Carlson does not explicitly teach a photo-melting composition as presently claimed, Carlson does teach that disulfide bonds of the crosslinked polymer are reversible, i.e., meltable (Carlson; [0044]). Because the compositions of Carlson comprise the claimed components, and because there is no evidence of record to the contrary, the Examiner maintains that the compositions of Carlson would inherently meet the presently claimed “photo-melting” limitations.
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 either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). See MPEP 2112.01 (I).
Also note the new grounds of rejection under 35 USC 103 over Carlson in view of Leichner, over Carlson in view of Wang, over Carlson in view of Zeitels taken in view of evidence by Adv BioMatrix, and over Carlson in view of Zainal, due to Applicant’s claim amendments.
Therefore, Applicant’s Remarks have been fully considered, but are not deemed persuasive.
Conclusion
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.
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/CDL/ Examiner, Art Unit 1732
/CORIS FUNG/Supervisory Patent Examiner, Art Unit 1732
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