DETAILED ACTION
Claims 1, 4-10, 12-16 are currently pending. Claims 1 and 15-16 are currently under examination.
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 .
Withdrawn Rejections
The prior rejection of claim 15 under 112(b) is withdrawn in light of based on Applicant amended claim 15 to be one linear ordered collagen scaffold.
Examiner’s Note
Applicant's amendments and arguments filed 04/22/2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. In the Applicant’s response, filed 04/22/2026, it is noted that claim 16 has been amended and no new matter or claims have been added.
New Rejection:
The following rejection is newly applied based on Applicant’s cancelation of claim 3.
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.
Claim 16 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 16 depends from canceled claim 3. Dependence on a canceled claim leads to unclear metes and bounds of the claim as the scope of the claim cannot be determined. For examination purposes claim 16 will be examined as dependent on claim 1.
Claim 16 recites the limitation "the cross-linking agent" in first line. There is insufficient antecedent basis for this limitation in the claim. Clam 1 is directed to crosslinked biodegradable material, but does not contain reference to a crosslinking agent and thus does not have antecedent basis.
Maintained Rejections:
The following rejection are maintained.
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(s) 1 and 15-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2013/0230573 (previously applied) in view of Vega (Applicant provided IDS dated 12/04/2024) and CN 101979106 (Applicant provided IDS dated 12/04/2024).
Regarding claim 1, the limitation of a tissue engineering material for nerve injury repair, wherein the tissue engineering material for nerve injury repair is cadherin crosslinked biodegradable material, the biodegradable material is a collagen is met by the ‘573 publication teaching collagen structure comprising applying onto a surface solution of liquid crystalline collagen and a crosslinker to form a layered structure (abstract). The crosslinking groups are covalently crosslinked to the collagen [0020]. Crosslinkers are taught to include glutaraldehyde [0037]. The scaffold can be incorporated with therapeutic compounds or agents that modify cellular activity. The therapeutic compounds can be attached to the scaffold and include cadherin ([0089], [0090], [0177]). The scaffold can be administered to subjects in need thereof for the regeneration of tissue such as connective tissue and nerve ([0099]-[0102]). The limitation of wherein the biodegradable material is collagen is met by the ‘573 publication teaching collagen which is crosslinked (abstract, [0020], [0037]).
The ‘573 publication does not specifically teach N-cadherin (claim 1).
Vega teaches three-dimensional conjugation of recombinant N-cadherin to hydrogel for neural growth (title). Hydrogel matrix three dimensionally functionalized with a controlled number of Fe-tagged recombinant N-cadherins (N-Cad-Fe). Cadherins were immobilized and oriented to the gel by anti-Fe-antibodies chemically coupled to gels. Functionalized gels generated a large fraction of neurons that are functional by increased intracellular calcium ion concentrations (abstract). Cadherins mediate intercellular adhesions and regulate different morphogenesis (page 6803, second column, first paragraph). Studies was the biological impact of a 3D hydrogel matrix functionalized with a controlled number of recombinant cadherin in regulating the activities of neurons towards 3D neural network formation. Coupling Fe-tagged cadherin to chemically conjugated Fe antibodies in a hydrogel would improve cadherin bioactivity in a 3D matrix (page 6804, first column). Chemical conjugation of the N-Cad-Fe to the alginate hydrogel was taught (page 6804, second column, last paragraph). The N-Cad was taught a chemically linked to the gel or using an Fe antibody as a linker (6805, second column).
The combination of references does not specifically teach linear ordered collagen scaffold (claim 1).
The ‘106 publication teaches biological material for rehabilitating spinal cord injury comprising crosslinking ordered collagen material to form an ordered collagen material crosslinked with 151 IgG and incubating with neurotrophic factor. The biological material can promote nerve regeneration and eliminate the inhibited factor of nerve growth regeneration (abstract). The scaffold can be a bridge for the growth of axis cylinder and plays the effect of guiding axon growth (page 2, middle page). Chemical crosslinking using suflosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboyxlate (Sulfo-SMCC) and 2-iminothiolanel_ICL (Trauts’s Reagent) is taught. Linear ordered collagen scaffolds are taught as used to form the material (page 4), reading on claims 16.
Regarding claim 15, the ‘106 publication teaches collagen-based materials having a length of 6mm and a diameter of 4mm: 151IgG of 2-6 ug to form a repair preparation material (claims 1-5). The ‘573 publication teaches the cross-sectional diameter in the range of about 2 microns to 70 microns of collagen fibers [0145]. Vega teaches hydrogels with biochemical conjugation of N-Cad-FC. Increased neuronal extension into the microchannel greater N-Cad densities, due to the enhanced mass transfer of the GC antibody and N-Cad-FC. Orchestrated control of N-CAD binding and the microstructure of the gel created a gel matrix to promote adhesion and growth of neuronal cells. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Vega teaches the amount of N-CAD to the matrix material is optimizable parameter, and the ‘573 publication teaches the diameter of the collagen fibers to be an optimizable parameter by teaching a range.
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 use N-cadherin attached to a crosslinked collagen scaffold as the ‘573 publication teaches crosslinked collagen scaffold which may contain cadherin attached to the scaffold and Vega specifically teaches N-Cad being attached to a hydrogel. One of ordinary skill in the art would be motivated to use N-Cadherin on the cross-linked collagen taught by the ‘573 publication because Vega teaches N-cadherin being used for neuronal growth and the ‘573 publication teaches the scaffold being used for nerve tissue. One of ordinary skill in the art before the effective filing date of the claimed invention would have a reasonable expectation of success as the ‘573 publication teaches attached cadherin to the scaffold and Vega teaches specifically N-Cadherin. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use known crosslinking agents such as Trauts reagent and Sulfo-SMCC as taught by the ‘106 publication for the crosslinking taught by the combination of the ‘573 publication and Vega as Vega teaches the desire for chemical conjugation of N-Cadherin to collagen and the ‘106 publication teaches the use of Sulfo-SMCC and Traut’s Reagan to cross-link to collagen material.
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 use the linear ordered collagen as taught by the ‘106 publication for the collagen scaffold as taught by the ’573 publication because the ‘106 publication teaches crosslinked collagen scaffolds use of axon growth and the ‘573 publication teaches the desire for a crosslinked collagen scaffold to be used for nerve regeneration. One of ordinary skill in the art would have a reasonable expectation of using the collagen scaffolds of the ‘106 publication for those of the ‘573 publication as both the ‘106 publication and the ‘573 publication are directed to collagen scaffolds used for nerve growth.
It would have been obvious to one of ordinary skill in the art to substitute a first crosslinked collagen scaffold as taught by the ‘573 publication with a second cross-linked linear collagen scaffold as taught by the ‘106 publication with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06.
Response to Arguments:
Applicant’s arguments have been fully considered and are not deemed to be persuasive.
103: the ‘573 publication in view of Vega and the ‘106 publication
Applicant argues the claims are not merely the combination of a collagen scaffold and a bioactive molecule, it is a N-cadherin covalently crosslinked biodegradable material, wherein the biodegradable material is a linear ordered collagen scaffold. Due to the covalently crosslinking, N-cadherin acts not only as a biological cue but also as a structural enhancer that physically alters the mechanical properties of the linear ordered collagen.
In response, the instant claim requires “N-cadherin covalently crosslinked biodegradable material”. This language allows for N-cadherin covalently crosslinked to the biodegradable material, N-cadherin and a covalently crosslinked biodegradable material or N-cadherin covalently crosslinking the biodegradable material. The structural relationship between the N-cadherin and the biodegradable material is not clearly claimed, thus all interpretations listed above read on the instant claims, and are not limited to the single interpretation argued by Applicant, wherein N-cadherin provides structural enhancement to the linear ordered collagen.
Applicant points to figures 1F and 1G wherein N-cadherin covalently crosslinked linear ordered collagen scaffold (LOCS-Ncad) of the present invention exhibits remarkably improved tensile modulus compared to unmodified linear of ordered collagen scaffold. None of the references cited teach or suggest covalently crosslinking N-cadherin to linear ordered collagen scaffold would result in such significant enhancement of the material mechanical properties.
In response, the data presented is for the specific structure wherein Traut’s Reagent is and Sulfo-SMCC is used to covalently link the N-cadherin to LOCS. As discussed above the instant claims do not clearly claim the structure tested and thus are not commensurate in scope with the provided data.
Applicant argues the ‘573 publication teaches crosslinking collagen fibers with agents like glutaraldehyde but does not teach covalently crosslinking a large protein like N-cadherin into the network to increase its tensile modulus.
In response, the ‘573 publication teaches crosslinked collagen with attached cadherin ([0020], [0089]). Applicant is referred to the above discussion regarding the breadth of the instant claims, wherein covalently crosslinked collagen and cadherin attached would meet the structure claimed.
Applicant argues Vega teaches conjugating N-cadherin to an alginate hydrogel which has different structure and does not teach improving the tensile strength. The ‘106 publication teaches crosslinking a linear ordered collagen scaffold with an antibody but does not teach such crosslinking dramatically improves tensile strength, nor does it suggest N-cadherin to achieve such an effect. Applicant argues unexpected results.
In response, the data presented is for the specific structure wherein Traut’s Reagent is and Sulfo-SMCC is used to covalently link the N-cadherin to LOCS. As discussed above the instant claims do not clearly claim the structure tested and thus are not commensurate in scope with the provided data.
Applicant argues Vega’s data and explicit conclusions would have discouraged a person of ordinary skill in the art as of the priority date of the present application from pursuing the covalent-linking path. Vega reports “cells cultured in the microchannels with chemically conjugated N-Cad-Fc aggregated. In contrast cells cultured in biochemically conjugated channels display neuronal extensions along microchannels”, “..neural cells cultured in the micro channels gel chemically bound with N-Cad-Fc developed few numbers of interconnected neurons with lower calcium signals and these results indicate that microchannel alginate gels biologically modified with N-Cad-Fc had greater effect in stimulating cell adhesion neuronal activity and overall neural network formation”. Vega does not merely express a preference but provides experimental evidence that the covalent approach is detrimental to the desired outcome.
In response, as Applicant confirms Vega teaches covalent attachment of N-cadherin to a hydrogel substrate. Additionally, the ‘573 publication teaches a collagen structure to which cadherin is attached (abstract, [0089], [0090], [0177]). Vega teaching a preference for biochemically bonding does not teach away from the non-covalent binding of cadherin to a substrate being taught, rather teaches a lesser affect, which is not a teaching away. “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).” (see MPEP 2123). Further, “the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).” (see MPEP 2141.02).
Conclusion
No claims are allowed.
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.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613
/BRIAN-YONG S KWON/Supervisory Patent Examiner, Art Unit 1613
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