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
This action is in response to papers filed May 12, 2026. Applicant’s reply to the restriction/election requirement of March 27, 2026 has been entered. Claims 5 and 22 have been amended, and claims 7, 8, 14, 15, 23-32, and 35-38 have been canceled. Claims 1-6, 9-13, 16-22, 33, and 34 are pending in the application.
Priority
Applicant’s claim for the benefit of a prior-filed WIPO International Application No. PCT/US2022/077140, filed September 28, 2022 under 35 U.S.C. 365(c), which claims the benefit of prior-filed U.S. Provisional Patent Application No. 63/249,353, filed September 28, 2021 under 35 U.S.C. 119(e), is acknowledged.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-6 and 9-11, is hereby acknowledged. Applicant’s elections of i) “augmented hydrogel matrix” as the species of luminal matrix, ii) “tyrosine-derived” as the species of biodegradable polymer group, iii) “collagen” as the species of polymer, iv) “growth factor” as the species of additional constituent in the augmented hydrogel matrix, v) “fibroblasts” as the species of system further constituent, vi) “3D printed microdevice” as the species of means of seeding fibroblasts, and vii) “the resorbable fibers are loaded into the lumen, then a suspension of Schwann cells is added to the lumen, and the resorbable fibers are cultured with Schwann cells within the lumen” as the species of order of culturing and loading of resorbable fibers and Schwann cells are all also acknowledged. The Examiner has determined that claims 1-6 and 9-11 read on the elected subject matter.
The traversal is on the ground(s) that “the Restriction Requirement is in error to the extent it concludes that the asserted common special technical feature is disclosed in the cited prior art”; that one aspect of the common special technical feature is “fibroblasts on the exterior surface of the conduit”; and that “Chen…does not disclose the claimed architecture of fibroblasts seeded on the exterior surface” and “Olausson…does not disclose the claimed electrospun biodegradable polymer conduit having Applicant’s recited cellular organization”.
These grounds for traversal are not found persuasive for the following reasons:
1. The restriction/election requirement mailed March 27, 2026 is based on the claim set filed March 28, 2024, not on the current claim set amended after the fact.
2. The special technical feature common to all of Groups I-V is “a nerve regeneration graft comprising an electrospun, biodegradable polymer conduit having an exterior surface and a lumen, and a hydrogel matrix and Schwann cells that fills the lumen”. The limitation of “fibroblasts on the exterior surface of the conduit” was not a special technical feature common to all of Groups I-V. For example, Groups IV and V did not require this feature.
Accordingly, claims 12, 13, 16-22, 33, and 34 are hereby withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected subject matter, there being no allowable generic or linking claim. The restriction/election requirement is still deemed proper, maintained, and is therefore made FINAL.
Applicant timely traversed the restriction (election) requirement in the reply filed on May 12, 2026. Claims 1-6 and 9-11 are under examination.
Claim Objections
Claims 4-6, 9, and 10 are objected to because the term “claim” in the preamble should not be capitalized.
Claim 9 is further objected to for improper Markush format, including the extraneous colon between “consisting of” and “RADA-16”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-6 and 9-11 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.
Claim 1 stipulates that the “system” comprises “a hydrogel matrix or augmented hydrogel matrix and Schwann cells”, which renders the claim indefinite for the following reasons:
1. First, due to poor sentence structure and punctuation, one of ordinary skill in the art cannot definitively ascertain if the two alternatives are “hydrogel matrix” or “augmented hydrogel matrix and Schwann cells”, or rather are “hydrogel matrix and Schwann cells” or “augmented hydrogel matrix and Schwann cells”.
2. The term “augmented” is not defined by the claim, is rather arbitrary and subjective; and one of ordinary skill in the art cannot definitively ascertain the requisite difference between “a hydrogel matrix” and “an augmented hydrogel matrix”, and what elements not in “a hydrogel matrix” are necessarily in “an augmented hydrogel matrix”, and/or what elements that are in an “augmented hydrogel matrix” are necessarily excluded from “a hydrogel matrix”. One of ordinary skill in the art thus cannot make heads or tails out of the metes and bounds of the claimed subject matter.
Claim 4 stipulates in a wherein clause that “the electrospun biodegradable polymer is a tyrosine-derived or tyrosol-derived polymer”. One of ordinary skill in the art cannot definitively ascertain the metes and bounds of “tyrosine-derived” polymer and “tyrosol-derived” polymer. Indeed, it would seem that just about any polymer could be “derived” from tyrosine or tyrosol. One of ordinary skill in the art cannot definitively ascertain whether “tyrosine-derived” polymers necessarily include or necessarily exclude tyrosine? In the former case, do “tyrosine-derived” polymers include at least one tyrosine residue, or do they include only tyrosine resides?
Claim 6 stipulates in a wherein clause that the Schwann cells are “substantially” evenly distributed in the matrix. The term “substantially” is not defined by the claim, and is rather arbitrary and subjective. One of ordinary skill in the art cannot definitively ascertain whether “substantially evenly” necessarily includes or excludes “evenly”, and how “uneven” can the distribution get and still be “substantially even”.
Claim 9 is indefinite for the following reasons:
1. Claim 9, which depends from claim 1, stipulates in a wherein clause the requisite constituents of “the augmented hydrogel matrix”, which is the alternative to the “hydrogel matrix” in claim 1. One of ordinary skill in the art cannot definitively ascertain if these recited requisite elements, or some fraction thereof, of the “augmented hydrogel matrix” are also necessarily excluded from the “hydrogel matrix” alternative.
2. Claim 9 contains the acronym “RADA” which is not defined by the claim. Claims must stand alone to define the invention, and should not rely on the specification, drawings, or extraneous materials.
3. Claim 9 is in improper Markush format and thus one of ordinary skill in the art cannot definitively ascertain the metes and bounds of the claimed subject matter. Applicant is advised that a proper Markush claim has the general format “selected from the group consisting of A, B, C, and D”, not “selected from the group consisting of: A, B, C, or D”.
4. Claim 9 recites the limitation “guidance cue”, which is not defined by the claim. One of ordinary skill in the art cannot definitively ascertain the metes and bounds of “guidance cue” and which chemical compounds fall within the purview of “guidance cue” and which do not, and at what concentrations.
5. Claim 9 recites the limitation “other chemical agent”, which is not defined by the claim. One of ordinary skill in the art cannot definitively ascertain what “other chemical agent” is necessarily included, and thus cannot definitively ascertain the metes and bounds of the claimed subject matter.
Claim 10 stipulates in a wherein clause that the “system further comprises fibroblasts, other supporting cells, or any combination thereof”, which renders the claim indefinite. The limitation “other supporting cells” is not defined by the claim, and appears to be entirely arbitrary and subjective. One of ordinary skill in the art cannot definitively ascertain what cells are “supporting cells” and what cells are not, and what “supporting cells” are necessarily included in the claim. Moreover, one of ordinary skill in the art cannot definitively ascertain whether “any combination” includes fibroblasts, or whether “any combination” can merely include a set of arbitrary and undefined “other supporting cells”.
Claims 2-6 and 9-11 are (also) indefinite for depending from an indefinite claim.
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 1-6, 9, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Zhu et al. (Tissue Engineering: Part C. 2011; 17: 705-715), in view of Wang et al. (Int J Biol Sci. 2017; 13: 1507-1519), and Nair et al. (Bioresearch Open Access. 2014; 3(5): 217-225).
Applicant Claims
Applicant’s elected subject matter is directed to a nerve regeneration conduit comprising i) an electrospun exterior surface comprising a first layer comprising aligned biopolymer fibers, and a second layer comprising unaligned (i.e. random) biopolymer fibers; ii) a layer of fibroblasts seeded to the exterior surface at a concentration of about 1.0 x 105 to about 1.0 x 106 cells/cm2; and iii) an interior lumen comprising collagen, Schwann cells, fibroblasts, and a growth factor.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Zhu et al. disclose a nerve regeneration conduit comprising an electrospun exterior surface comprising a first layer comprising aligned biopolymer fibers, and a second layer comprising unaligned (i.e. random) biopolymer fibers, and an interior lumen.
Wang et al. disclose that the development of nerve conduits with the optimal seeding cells in the lumen is a high priority in peripheral nerve regeneration, and that the co-transplantation of nerve fibroblasts and Schwann cells at a 1:2 ratio had a significantly positive effect on nerve regeneration and functional recovery; and that this effect is mediated in part by the increased presence of extracellular matrix components and growth factors like NGF and BDNF.
Nair et al. disclose that an electrospun biodegradable scaffold in which fibroblasts have been seeded on the surface at a density of 2 x 104 cells/cm2 better maintains its shape and dimension over time, exhibits greater physical strength and stability, and exhibits a higher tensile strength, which were shown to be dependent on the degree of fibroblast attachment, proliferation, and deposition of ECM protein.
Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Zhu et al. do not explicitly disclose that the nerve regeneration conduit comprises a layer of fibroblasts seeded to the exterior surface, and that the interior lumen comprises collagen, Schwann cells, fibroblasts, and a growth factor. These deficiencies are cured by the teachings of Wang et al. and Nair et al.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to combine the respective teachings of Zhu et al., Wang et al., and Nair et al., outlined supra, to devise Applicant’s claimed product.
Zhu et al. disclose a nerve regeneration conduit comprising an electrospun exterior surface comprising a first layer comprising aligned biopolymer fibers, and a second layer comprising unaligned (i.e. random) biopolymer fibers, and an interior lumen. Since Wang et al. disclose that the development of nerve conduits with the optimal seeding cells in the lumen is a high priority in peripheral nerve regeneration, and that the co-transplantation of nerve fibroblasts and Schwann cells at a 1:2 ratio had a significantly positive effect on nerve regeneration and functional recovery; and that this effect is mediated in part by the increased presence of extracellular matrix components and growth factors like NGF and BDNF; and since Nair et al. disclose that an electrospun biodegradable scaffold in which fibroblasts have been seeded on the surface at an initial density of e.g. 2 x 104 cells/cm2 better maintains its shape and dimension over time, exhibits greater physical strength and stability, and exhibits a higher tensile strength, which positive effects were shown to be dependent on the degree of fibroblast attachment, proliferation, and deposition of ECM protein; one of ordinary skill in the arty would thus be motivated to seed a layer of fibroblasts to the external surface of the Zhu et al. conduit; and to include the combination of fibroblasts and Schwann cells at a 1:2 ratio in the lumen, together with an ECM protein such as collagen and a growth factor, such as NGF, with the reasonable expectation that the resulting nerve regeneration conduit will maintain its shape and dimension over time, exhibit greater physical strength and stability, exhibit a higher tensile strength, and better promote a significantly positive effect on nerve regeneration and functional recovery.
From the teachings of Nair et al., one of ordinary skill in the art would understand that the density at which fibroblasts are seeded on the exterior surface of the conduit is a results-effective variable, as discussed supra, and thus would optimize the seeding density to arrive at a density of e.g. about 1.0 x 105 to about 1.0 x 106 cells/cm2.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Potentially Allowable Subject Matter
Claim 11 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID BROWE whose telephone number is (571)270-1320. The examiner can normally be reached Monday - Friday, 9:30 AM to 6 PM EST.
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/DAVID BROWE/Primary Examiner, Art Unit 1617
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