DETAILED ACTION
Claims 1, 3-10, 12-16 are currently pending. Claims 1, 3 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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/19/2025 has been entered.
Examiner’s Note
Applicant's amendments and arguments filed 09/19/2025 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 09/19/2025, it is noted that claims 1 and 15 have been amended and no new matter or claims have been added.
New Rejections:
The following rejections are newly applied based on Applicant’s claim amendments.
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 15 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 15 recites “per unit” of the linear ordered collagen scaffold. It is unclear what “unit” is limited to. The limitation of “unit” has unclear metes and bounds as it is a relative term which is not defined by the instant specification or claims. For examination purposes the limitation will be interpreted to be directed to one section collagen scaffold of the diameter and length claimed having a concentration of 1-6 ug.
Claim Rejections - 35 USC § 112 (d)
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.
Claim 3 is 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 3 is directed to the N-cadherin is covalently crosslinked with the linear ordered collagen scaffold. Instant claim 1, from which it depends is directed to the N-cadherin covalently crosslinked biodegradable material wherein the biodegradable material is linear ordered collagen scaffold. Thus instant claim 3 does not further limit instant claim 1 which contains N-cadherin covalently crosslinked linear ordered collagen. 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.
Modified Rejection:
The following rejections are modified based on Applicant’s claim amendments.
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, 3 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]. Bega 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. Further Applicant is referred to the 112(b) rejection above regarding claim 15.
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.
Applicant argues Bega’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).
Applicant argues impermissible hindsight. The ‘106 publication teaches using Trauts reagent and Sulfo-SMCC to link a completely different protein, 151 IgG, an antibody to a collagen scaffold. The functional structure is vastly different from N-cadherin.
In response, 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.
Applicant argues unexpected results. Contrary to the expectation from Vega, the claimed material demonstrates superior in vivo biological function, including efficient migration of endogenous neural stem cells, promotion of their differentiation into neurons and recovery of motor functions. The covalent crosslinking of N-cadherin to the linear ordered collagen scaffold results in a significant and unexpected improvement in the material’s mechanical properties. The specification demonstrates that compared to an unmodified LOCS, the claimed LOCS-Ncad has remarkably improved tensile modulus and maintains a stable linear state when immersed in saline. A person having ordinary skill in the art as of priority date of the present application, reading Vega would have expected covalent linking to impair biological function, they would have not expected it to simultaneously improve mechanical properties while also yielding superior in vivo biological outcomes.
In response, it appears the examples present finding comprising the covalently bonded N-cadherin to linear collagen as compared to crosslinked linear collagen comprising BSA. Vera teaches cell-cell adhesion controlled by intercellular cadherin junction plays an important role in the quality of the resulting engineering tissues. The use of N-Cad was taught to increase intracellular calcium ion concentration, increase glial to neuron ratio and regulate phenotypic activities of tissue forming cells (abstract). Vera teaches microchannel alginate gels modified with N-CAD had a great effect in stimulating cell adhesion, neural activity and overall neural network formation (page 6809, second column, last paragraph). Thus the positive benefits of adding N-cadherin to regulate cellular emergent behavior involved in tissue/organ development, wound healing and pathology (page 6810, first column) are not unexpected.
Conclusion
No claims are allowed.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613