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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 22, 2025 has been entered.
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant’s amendment filed May 22, 2025 is acknowledged. Claims 1-11 and 17-18 are canceled. Claims 12, 14, 16 and 25 are amended. Claims 12-16 and 19-25 are pending in this application and under examination in this office action.
4. Applicant’s arguments filed on May 22, 2025 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Claim Rejections/Objections Withdrawn
5. The rejection of claims 12-16 and 19-25 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in response to Applicant’s amendment to the claims and cancellation
New Grounds of Rejection Necessitated by the Amendment
The following rejections are new grounds of rejections necessitated by the amendment filed on May 22, 2025.
Claim Rejections - 35 USC § 112
6. 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 12-16 and 19-25 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 pre-AIA the applicant regards as the invention.
Claims 12-16 and 19-25 are indefinite because:
i. The limitation “such that an area where neuroblasts are present is linked to the affected area” recited in independent claims 12, 14 and 25 is unclear. It is unclear what the limitation means and what Applicant intended to include within the scope of the claims. It is unclear whether the limitation means that “neuroblasts in the ventricular-subventricular zone (V-SVZ) are recruited to the affected area” or “neuroblasts from any area in the body traffic to an area via specific migration patterns and paths, and such specific migration and paths are linked to the affected area”. For examination purposes, the limitation is interpreted as “such that neuroblasts in the ventricular-subventricular zone (V-SVZ) are recruited to the affected area”.
Claim Rejections - 35 USC § 103
7. 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 12-16 and 19-25 are rejected under 35 U.S.C. 103 as being unpatentable over Ellis-Behnke et al. (US2005/0287186; issued as US7846891, cited previously) in view of Reiner et al. (Cell Stem Cell; 2018, 22; 128-137, cited previously), Yu et al. (Biomaterials, 2010; 31:5287-5296, cited previously), Vega et al. (J. Mater. Chem, 2016; 4:6803, cited previously) and Shapiro et al. (Cold Spring Harb. Perspect. Biol.2009;1:a003053, cited previously) and evidentiary references: Klinigener et al. (J. Neurosci. 2014; 34:9590-9606) and Ajoka et al. (Tissue Eng. 2015; 21:193-201).
Claims 12-16 and 19-25 are drawn to methods for treatment of a neonatal brain injury selected from the group consisting of hypoxic encephalopathy, hypoxic ischemic encephalopathy, ischemic brain injury and brain injury due to physical damage, comprising promoting a migration of neuron cells to an affected area by transplanting into the brain a material comprising N-cadherin-Fc-carrier such that an area where neuroblasts are present is linked to the affected area; wherein N-cadherin-Fc-carrier contains a protein having all of EC1, EC2, EC3, EC4 and EC5 domains of N-cadherin. Claims 13 and 15 are drawn to the similar methods above and also include transplanting neuronal cells derived from pluripotent stem cells together with the material in the method of independent claims 12 and 14. Dependent claims are directed to wherein the N-cadherin-Fc-carrier has a homophilic binding capacity to N-cadherin (claim 16), wherein the carrier is a porous body (claim 19), a biomaterial or biocompatible polymer carrier (clams 20-21), wherein the biomaterial is a protein, a polysaccharide, collagen (claims 22-23)
Ellis-Behnke (US2005/0287186) teaches a method of enhancing neural regeneration or repair to treat brain injury by introducing a biocompatible scaffold/material/composition at the site of injury in a patient with brain injury, wherein the biocompatible scaffold comprises a nanoscale structured material (i.e. a carrier) comprising self-assembling peptides including RADA16-I and incorporating additional regeneration promoting factors including N-cadherin encapsulated in polymeric nanoparticles or microparticles which are incorporated into the scaffold/material/composition (see abstract; paragraphs [0006]-[0012]; [0047]-[0049], [0062]-[0063]; [0067]- [0101]-[0105]; [0111], in particular). Ellis-Behnke also teaches using the biocompatible scaffold/material/composition together with cells to produce molecules that promote regeneration or create environment permissive for regeneration, wherein the cells include Schwann cells, CNS glial cells, macrophages, and olfactory ensheathing cells, and different progenitor cells including neural progenitor cells, glial progenitor cells, and/or stem cells, as in claims 13 and 15 (see paragraphs [0116]-[0118]). Ellis-Behnke also teaches that the carrier is a porous body as in claim 19 (see paragraph [0067]), a biomaterial or biocompatible polymer carrier as in clams 20-21, or a protein/polysaccharide biomaterial including collagen as in claims 22-23 (see paragraphs [0130]-[0133], in particular).
The introduction of the biocompatible scaffold/material/composition comprising RADA16-I and incorporating N-cadherin encapsulated in polymeric nanoparticles or microparticles that are incorporated into the scaffold/material/composition at the site of injury in a patient with brain injury disclosed by Ellis-Behnke inherently promotes migration of neuroblasts or neuron cells to an affected area as evidenced by Klinigener et al. (see p.9590, abstract; J. Neurosci. 2014; 34:9590-9606) and Ajoka et al. (see p. 193, abstract; Tissue Eng. 2015; 21:193-201).
But Ellis-Behnke does not teach neonatal brain injury, N-cadherin-Fc-carrier, wherein the N-Cadherein-Fc-carrier containing a protein having all EC1-EC5 domains of N-Cadherin recited in clams 12, 14, 16, and 25, or gelatin as a carrier in clams 23-24.
Reiner et al. teaches that N-cadherin gelatin sponges promote V-SVZ-derived neuronal or neuroblast migration after neonatal brain injury to treat neonatal brain injury as in claims 12, 14, 16 and 23-25 (see p. 3, 3rd col.; p. 4, figure 1, in particular).
Yue et al. teach that a N-Cadherin-Fc fusion protein comprising the entire extracellular domain of N-cadherin fused to IgG-Fc (N-Cad-Fc) as in independent claims 12, 14 and 25 can stably adsorb to hydrophobic surface and that P19 embryonal carcinoma cells or MEB5 neural stem cells cultured on N-Cad-Fc-coated surface differentiated into neural cells (see p. 5287, abstract; p.5288, material and methods-2.1~2.4; p. 5289-5296).
Vega et al. teach that N-Cad-Fc immobilized on a 3D hydrogel matrix provides better environments for neuronal growth, wherein the 3D hydrogel matrix is conjugated with a controlled number of N-Cad-Fc as in independent claims 12, 14 and 25 (see p. 6803, abstract; p. 6804; p. 6805-6810, scheme 1, figures 1-2).
Shapiro et al. teach that EC1 domain in the extracellular domain of N-cadherin is responsible for adhesive binding to partners of N-cadherin and EC1-EC5 domains are required for Ca2+ binding for cell adhesion as in independent claims 12, 14 and 25 (p. 2, col. 2, figure 1; p. 4-5).
A person of ordinary skill in the art would have recognized that selecting and applying the known N-Cad-Fc-carrier containing a protein having all EC1-EC5 domains of N-Cadherin and wherein the carrier includes a gelatin sponge or collagen, a polymeric carrier or a protein or polysaccharide biomaterial and the known technique disclosed by Reiner, Yue, Vega and Shapiro to the Ellis-Behnke’s method would have yielded the predictable result of promoting neuronal migration neonatal brain injury or treating neonatal brain injury, and resulted in an improved method of treating neonatal brain injury.
Using the known N-Cad-Fc-carrier containing a protein having all EC1-EC5 domains of N-Cadherin and a carrier including a gelatin sponge or collagen, a polymeric carrier or a protein or polysaccharide biomaterial in the Ellis-Behnke’s method would promote neuronal or neuroblast migration in neonatal brain injury or treat neonatal brain injury, and expand application of the Ellis-Behnke’s method, and would increase patient’s satisfaction with treatment of neonatal brain injury using N-Cad-Fc-carrier because Ellis-Behnke and Reiner teach using N-cadherin gelatin sponges to promote V-SVZ-derived neuronal migration after neonatal brain injury to treat neonatal brain injury, and Reiner, Yue, Vega and Shapiro teach N-cad-Fc fusion protein immobilized on a carrier including a gelatin sponge or collagen, a polymeric carrier or a protein or polysaccharide biomaterial and their benefits of providing better environments for neuronal growth and neuronal differentiation.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known N-Cad-Fc-carrier containing a protein having all EC1-EC5 domains of N-Cadherin and wherein the carrier includes a gelatin sponge or collagen, a polymeric carrier or a protein or polysaccharide biomaterial and the known technique disclosed by Reiner, Yue, Vega and Shapiro to the Ellis-Behnke’s method o treat neonatal brain injury or promote neuronal or neuroblast migration, and yield the predictable result of treating neonatal brain injury and promoting neuronal or neuroblast migration neonatal brain injury. See KSR International Co. V. Teleflex Inc. 82 USPQ2d 1385 (2007) In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980); In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992), Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) and In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) and also see MPEP § 2143. 01-I, MPEP § 2144.06 and MPEP §2144.07.
Conclusion
8. NO CLAIM IS ALLOWED.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached on Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
February 7, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675