DETAILED ACTION
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 .
Claim Status
Claims 1-15 and 34-51 are pending.
Claims 42-44 have been amended.
Claims 45-51 are newly added.
Election/Restriction
Applicant’s election without traverse of Group II (claims 34-44) and new claims 45-51 in the reply filed on 5/5/2026 is acknowledged.
Claims 1-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/5/2026.
Applicant’s election without traverse of i) 2-hydroxy-4’-(2-hydroxyethoxy)-2-methylpropiophenone (photoinitiator) ii) oxidized methacrylate alginate (natural polymer macromer) and iii) BMP-2 (growth factor) in the reply filed on 5/5/2026 is acknowledged.
Claims 34-51 are under consideration to the extent that the photoinitiator is 2-hydroxy-4’-(2-hydroxyethoxy)-2-methylpropiophenone, the natural polymer macromer is oxidized methacrylate alginate, and the growth factor is BMP-2, i.e. applicant’s elected species.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/12/2023 have been received. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 34 is objected to in reciting “the crosslinkable bioactive agent coupling polymer macromer” (line 5), which should be amended to “the crosslinkable bioactive agent coupling polymer macromers”, consistent with line 4.
Claim 38 is objected to in reciting “… acrylated and/or methacrylated, natural polymer macromers…” (line 2), which appears to have an aberrant comma. This should be amended to “… acrylated and/or methacrylated natural polymer macromers…” consistent with claim 37 in order to rectify this issue.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 38, 39, 40, 43, and 46 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 38-39 are rejected as being indefinite in reciting "acrylated and /or methacrylated, natural polymer macromers" in claim 38 (first senetence). There is insufficient antecedent basis for this limitation in the claim. As claim 34, which 38 depends on, does not recite any acrylated and/or methacrylated natural polymer macromers. Claim 37 recites “acrylated and/or methacrylated natural polymer macromers.” If Applicant intended to refer to the macromers as recited in claim 37, correction to claim 38 is advised to correct the lack of antecedent basis stemming from the lack of reference to “acrylated and/or methacrylated natural polymer macromers” in claim 34.
Claims 40, 43, and 46 recite the limitation "the bioactive agent" in each claim. There is insufficient antecedent basis for this limitation in the claim. Base claim 34 recites “at least one bioactive agent” which encompasses multiple bioactive agents. Thus, it is unclear whether “the bioactive agent” is referring to just one, more than one, or all of the “at least one bioactive agent[s].” Amending claims 40, 43, and 46 to recite “the at least one bioactive agent” would overcome this rejection.
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.
Claims 34-38 and 41-51 is/are rejected under 35 U.S.C. 103 as being unpatentable over Alsberg (US20160008475A1, published 1/14/2016).
Claim Interpretation – it is noted that claim 34-38 and 41-51 are directed to a composition for creating a hydrogel (i.e. development of monomers and precursors to the hydrogel prior to crosslinking). Claims 49 -51is interpreted as the hydrogel after crosslinking.
Alsberg teaches a composition that includes a plurality of coacervate micro and/or nanodroplets of oxidized alginate and a methacrylated gelatin as a crosslinkable base polymer to be used as a precursor to a hydrogel. These micro/nanodroplets are further functionalized into a hydrogel with desirable properties. These components “can provide localized, sustained, and/or controlled release of bioactive agents…” (paragraph [0003]). This composition that is intended as a precursor to a hydrogel is made up of functionalized naturally occurring polysaccharide monomers, said monomers being oxidized alginate (i.e. crosslinkable macromers). Alsberg teaches the composition of the hydrogel, and teaches that “the hydrogel matrix can include cross-linked oxidized methacrylated alginate” (paragraph [0005]). Alginate in and of itself is a natural polymer macromer that is further classified as a polysaccharide, based on its chemical structure. It is negatively charged as well, as it features negatively charged carboxylic acid groups.
This hydrogel matrix can further include a sufficient amount of a bioactive agent to produce a therapeutically beneficial result, and Alsberg reports that said bioactive agent is, in some embodiments, BMP-2 (paragraph [0054]). In other embodiments, the bioactive agent could be heparin, or heparin-binding domains (paragraph [0052]). In this case, methacrylated heparin was used to incorporate the heparin into the hydrogel (paragraph [0086]). This approach could be used for other bioactive agents (i.e. a crosslinkable bioactive agent). The bioactive agent may be incorporated into the hydrogel in such a way that the “hydrogel… could be utilized for the regulated spatiotemporal presentation…” of the bioactive agent (paragraph [0102]).
In terms of producing the hydrogel itself, Alsberg discloses that UV light may be used in the presence of a photoinitiator, and gives examples of said photoinitiatiors, one of which is 2-hydroxy-4’-(2-hydroxyethoxy)-2-methylpropiophenone (paragraph [0050]) in order to crosslink the monomers and form the final composition. Alsberg continues with stating that the hydrogel can also be cytocompatible, and the hydrogel may further comprise at least one cell embedded in it, but can be a plurality of cells (paragraph [0060]). When referring to cells, Alsberg lists any kind of progenitor cell as an example, including but not limited to totipotent, pluripotent, and multiponent stem cells. In fact, Alsberg states that progenitor cells and stem cells are used interchangeably (paragraph [0024]).
The specific combination of features claimed is disclosed within the broad generic teachings as taught by Alsberg, but such “picking and choosing” within several variables does not necessarily give rise to anticipation (Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989)). That being said, however, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious” (KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 U.S.C. 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ” (KSR at 1741). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton” (Id. at 1742).. Consistent with this reasoning, 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 apply the teachings of Alsberg and arrive at the instant invention as the raw materials that comprise the monomers, as well as the hydrogel, are identical. The teachings describe a composition to form a bioactive agent within a hydrogel developed from natural polysaccharide monomers (i.e. methacrylated alginate). Further, the hydrogel may comprise a photoinitiator (specifically 2-hydroxy-4’-(2-hydroxyethoxy)-2-methylpropiophenone) to begin the polymerization of the hydrogel in the presence of external stimulus, the stimulus being UV light. The hydrogel may also comprise at least one stem cell, as well as bioactive material that can by methacrylated to incorporate into the polymer. The bioactive material may be various potential actives, but of note from the teachings is BMP-2 and heparin. These teachings align with the instant invention. In light of Alsberg’s teachings, claims 34-38 and 41-51 are prima facie obvious.
Claims 39-40 are rejected under 35 U.S.C. 103 as being unpatentable over Alsberg (US20160008475A1, published 1/14/2016) as applied to claims 34-38 and 41-51 above, and further in view of Samorezov (Dual Ionic and Photo-Crosslinked Alginate Hydrogels for Micropatterned Spatial Control of Material Properties and Cell Behavior, published 4/9/2015).
Alsberg has been described supra.
However, Alsberg is silent regarding ionic crosslinking of the monomers (i.e. claim 39), and other non-covalent coupling techniques to incorporate the bioactive agent (i.e. claim 40).
This deficiency is made up for by the teachings of Samorezov.
Samorezov teaches hydrogels comprising methacrylated alginate, wherein ionic and UV light crosslinking techniques were used to polymerize the monomers of alginate (abstract). Samorezov uses calcium ions to crosslink the hydrogel between chains via the monomer’s negatively charged carboxylic acid groups (figure 1 demonstrates the ionic crosslinking). This technique may also be used for bioactive materials, as they can be functionalized with acrylate or methacrylate groups and incorporated into the crosslinked framework of the hydrogel both via non-covalent ionic crosslinking as well as covalent (discussion paragraph 5).
It would have been prima facie obvious before the effective filing date of the instant application to apply the dual crosslinking technique as taught by Samorezov to the hydrogel as taught by Alsberg. One skilled in the art would be motivated to do so as Samorezov reports that this technique stiffens regions of the hydrogel at different time points, allowing greater manipulation of the hydrogel as a whole (discussion paragraph 6). There would be a reasonable expectation of success in doing so as both Alsberg and Samorezov use the same methacrylated alginate monomers for their hydrogels, so the hydrogels are fundamentally and chemically identical in property. Therefore, inclusion of the calcium ionic crosslinking in terms of the hydrogel network and in terms of the bioactive material would have been obvious to one skilled in the art, and claims 39-40 are prima facie obvious.
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.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATTHEW RYAN BURKE whose telephone number is (571)272-8949. The examiner can normally be reached Mon-Fri. 8am-5pm.
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/MATTHEW RYAN BURKE/Examiner, Art Unit 1619
/DAVID J BLANCHARD/Supervisory Patent Examiner, Art Unit 1619
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