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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 October 22, 2025 has been entered.
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant’s amendment filed October 22, 2025 is acknowledged. Claims 1 and 5-6 are amended. Claims 1-7 are pending in this application. Election was made without traverse in the reply filed on December 16, 2024.
4. Claims 1-7 are under examination with respect to a lysine (K) at position 159 of SEQ ID NO: 24 or 51 substituted by an alanine (A), Serine (S) or Leucine (L) and dementia/vascular dementia/Alzheimer’s disease in this office action.
5. Applicant’s arguments filed on October 22, 2025 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Claim Rejections/Objections Maintained
In view of the amendment filed on October 22, 2025, the following rejections are maintained.
Claim Rejections - 35 USC § 112
6. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-7 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for activating GPr124/Reck/Fz/LRP-mediated signaling by Wnt7a (SEQ ID NO: 24/51), Wnt7a-aa1-278, Wnt7a-K190A and other variants of Wnt7a including a single mutation shown in Figure 7C, or triggering GPR124/RECK-dependent brain angiogenesis and restoring blood brain barrier based on GLUT1 expression in Wnt7aa-/-mutant zebrafish by Wnt7a-aa1-278 or Wnt7a-K190A or reducing stroke volume in an animal model of stroke that is induced by transient middle cerebral artery occlusion (tMCAO) by intravenous injection to the animal model of stroke a viral vector encoding mouse Wnt7aK190A (AAV-PHP-eB-CAG-mWnt7aK190A-p2A-EGFP), does not reasonably provide enablement for a method for restoring a blood brain barrier in a subject having all forms conditions or all forms of neovascular disorders or CNS disorders recited in claims 5-7 by administering to the subject a Wnt7 polypeptide comprising SEQ ID NO:51 with an amino acid substitution recited in claim 1 as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 1-7 as amended are drawn to a method of restoring a blood brain barrier in a subject in need thereof including a subject with disorder or a CNS disorder comprising neovascular dysfunction in a subject in need thereof, comprising administering to the subject a nucleic acid encoding a Wnt7a polypeptide or fragment thereof, wherein the Wnt7 polypeptide or fragment thereof comprises SEQ ID NO:51 with an amino acid substitution recited in independent claim 1.
The claims encompass restoring a BBB in all possible conditions and all forms of neovascular disorders or CNS disorders by the claimed nucleic acid encoding the claimed Wnt7 polypeptide or fragment thereof comprising SEQ ID NO: 51 with an amino acid substitution recited in independent claim 1 in view of paragraphs [0365]-[0367] of the published application.
Response to Arguments
On p. 6-7 of the response, Applicant argues that the rejection has been overcome in view of amendment to claim 1 by reciting restoring the BBB and the specification provides support for the enablement of the claimed method and cites paragraphs [0365]-[0366] and the recited CNS and neurovascular diseases in paragraphs [0005]-[0006]; [0076]; [0368] and [0374]-[0375].
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2164, MPEP §§2164.01-2164.06(b) & 2164.08, the specification provides insufficient guidance to enable a skilled artisan to practice the full scope of the claimed invention without undue experimentation because:
i. There is no well-established structural and functional relationship or correlation between triggering angiogenesis in the brain and the GLUT1 expression in the BBB of Wnt7aa-/-mutant ebrafish after expression of expression of mouse Wnt7a-aa1-278 or Wnt7a-K190A in the Wnt7aa-/-mutant zebrafish and pathogenesis or pathologies of all forms of neovascular disorders or CNS disorders caused by all possible mechanisms including CNS neurodegenerative diseases including dementia/vascular dementia/AD. There is also no well-established structural and functional relationship or correlation between the GLUT1 expression in Wnt7aa-/-mutant ebrafish after expression of expression of mouse Wnt7a-aa1-278 or Wnt7a-K190A in the Wnt7aa-/-mutant zebrafish and restoring the BBB in these diseases by the claimed Wnt7 polypeptide or fragment thereof comprises SEQ ID NO:51 with an amino acid substitution recited in independent claim 1.
ii. The specification provides no well-established structural and functional relationship or correlation between reducing stroke volume in a mouse model of stroke or triggering angiogenesis in the brain of by the Wnt7a-K190A and the pathogenesis or pathologies of other forms of neovascular disorders or CNS disorders caused by all possible mechanisms including CNS neurodegenerative diseases including dementia/vascular dementia/AD by the claimed Wnt7 polypeptide or fragment thereof comprises SEQ ID NO:51 with an amino acid substitution recited in independent claim 1.
iii. Each type of animal models of CNS neurological diseases or CNS neurodegenerative diseases or each type of animal models of AD only reflects part of pathogenesis of the disease as taught by Tayebati (see p. 106, 1st col, 2nd paragraph, Tayebati, Mech. Ageing Dev. 2006. 127: 100-8, cited previously) and Sarter (see p. 645, abstract, Sarter, Neurosci. and Biobehav. Rev. 2004. 28: 645-650, cited previously).
There is no well-established correlation between reducing stroke volume in the mouse model of stroke by the Wnt7a-K190A and treatment of other forms of neovascular disorders or CNS disorders caused by all possible mechanisms including CNS neurodegenerative diseases including dementia/vascular dementia/AD by the claimed Wnt7 polypeptide or fragment thereof comprises SEQ ID NO:51 with an amino acid substitution recited in independent claim 1.
There is also no well-established correlation between triggering angiogenesis in the brain and the GLUT1 expression in the BBB of Wnt7aa-/-mutant zebrafish and the treatment of other forms of neovascular disorders or CNS disorders caused by all possible mechanisms including CNS neurodegenerative diseases including dementia/vascular dementia/AD by the claimed Wnt7 polypeptide or fragment thereof comprises SEQ ID NO:51 with an amino acid substitution recited in independent claim 1.
iii. The specification provides insufficient guidance or evidence to demonstrate that Applicant can restore the BBB in a subject with all possible conditions or all forms of neovascular disorders or CNS disorders caused by all possible mechanisms including CNS neurodegenerative diseases including dementia/vascular dementia/AD by the claimed Wnt7a mutants as instantly claimed. Thus, it is unpredictable whether administration of the claimed Wnt7a mutants can treat or prevent all forms of neovascular disorders or CNS disorders caused by all possible mechanisms including CNS neurodegenerative diseases including dementia/vascular dementia/AD, indicating undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
Note that the scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without such guidance, it is unpredictable whether the BBB of all possible conditions or all forms of neovascular disorders or CNS disorders caused by all possible mechanisms including CNS neurodegenerative diseases including dementia/vascular dementia/AD can be restored by all of the claimed Wnt7a mutants; and thus the experimentation left to those skilled in the art is extensive and undue. See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Int. 1986). Thus, the skilled artisan cannot readily know how to use the claimed invention as currently claimed without further undue experimentation. In re Marzocchi, 439 F.2d 220, 223-24, 169 USPQ 367, 369-70 (CCPA 1971)” See MPEP § 2164.03.
Therefore, in view of the breadth of the claims, the lack of guidance in the specification, limited working examples, the unpredictability of inventions, and the current status of the art, undue experimentation would be required by a skilled artisan to perform in order to practice the claimed invention as it pertains to a method for treating including preventing all forms of neovascular disorders or CNS disorders caused by all possible mechanisms including CNS neurodegenerative diseases including dementia/vascular dementia/AD by administration of the claimed Wnt7a mutants.
Accordingly, the rejection of claims 1-7 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, lack of scope of enablement is maintained.
New Grounds of Rejection Necessitated by the Amendment
The following rejections are new grounds of rejections necessitated by the amendment filed on October 22, 2025.
Double Patenting
7. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-18 and 20-21 of copending Application No. 19/488303. Although the claims at issue are not identical, they are not patentably distinct from each other because the method recited in claims 16-18 and 20-21 of Application No. 19/488303 (the ‘303 Application) recite the same method steps and the same material, and appears to be directed to achieving the same goal, restoring the BBB.
Claims 1-7 of the instant Application claim a method of restoring the BBB in a subject in need thereof comprising administering to the subject a nucleic acid encoding a Wnt7 polypeptide or a fragment thereof capable of activating GPR124/RECK/Frizzled/LRP-mediated Wnt signaling, wherein the Wnt7 polypetide or fragment thereof comprises SEQ ID NO:51 with an amino acid substitution at different position including position 318 in SEQ ID NO:51.
Claims 16-18 and 20-21 of the ‘303 Application claim a method comprising administering to an individual in need thereof a mutant Wnt7 comprising an amino acid addition at its C-terminal end, having a length of 1-8 amino acids, and acting as an agonist in Gpr124 and Reck-dependent Wnt/b-catenin pathway for a gene therapy, a RNA therapy, for treatment of a neurovascular disorder, neuroinflammation disorder, or a CNS disorder including neurovascular dysfunction, glioblastoma, retinopathy that is a retinal vascular disease or disorder.
The nucleic acid encoding the mutant Wnt7 comprising an amino acid addition at its C-terminal end, having a length of 1-8 amino acids used in the method recited in the claims of the ‘303 Application meets the nucleic acid encoding the Wnt7 polypeptide or a fragment thereof recited in instant claims. The patients and the active steps and subjects with different diseases recited in the method of the ‘303 Application also meest the subject recited in instant claims. Thus, claims 1-7 of the instant Application are not patentably distinct from claims16-18 and 20-21 of the ‘303 Application because claims 1-7 of the instant Application are anticipated by claims 16-18 and 20-21 of the ‘303 Application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
April 3, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675