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 the papers filed June 4, 2026.
Election/Restrictions
Applicant’s reply filed 06/04/2026 to the Requirement for Restriction/Election mailed 02/04/2026 is acknowledged.
Applicant elected without traverse:
Group 1, drawn to a method of retargeting a recombinant herpes simplex vims (HSV) to a tumor cell, and a method of treating cancer thereby;
a GCN4 transcription factor, as the heterologous peptide; and
TMEFF2, as the tumor-associated antigen.
Rejoinder: After further consideration, the restriction requirement among alternative tumor-associated antigens is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 13, 15-16, 18-19, 43-44, 73-75, 79 and 82 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/04/2026.
Claim Listing
The instant claim listing was filed on 06/04/2026.
Claims 3-7, 9, 12, 14, 17, 21-39, 41-42, 45-72, 76-78, 80-81, 83-84 have been cancelled.
Claims 1-2, 8, 10-11, 13, 15-16, 18-20, 40, 43-44, 73-75, 79 and 82 are pending.
Claims 13, 15-16, 18-19, 43-44, 73-75, 79 and 82 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1-2, 8, 10-11, 20 and 40 are under examination.
Priority
The instant application 18/558,859 was filed on 11/03/2023. This application is a national stage of international application PCT/IB2022/054111 filed 05/04/2022, claiming priority based on U.S. Provisional Patent Application 63/184,283 filed 05/05/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/03/2024 and 10/24/2025 have been considered.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, or by applicant in an information disclosure statement (IDS), they have not been considered.
Claim Objections
Claim 1 is objected to because of the following informalities:
In claim 1, line 2, the phrase “TAA” should be “tumor associated antigen (TAA)” instead, such that the acronym is spelled out in the first instance of the claims.
Appropriate action is required.
Claim Rejections - 35 USC § 112
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 11 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 recites an anti-GCN4 scFv comprising (i) a heavy chain variable region (VH) comprised of HCDR1 (SEQ ID NO: 16), HCDR2 (SEQ ID NO: 17), and HCDR3 (SEQ ID NO: 18) and/or a light chain variable region (VL) comprised of LCDR1 (SEQ ID NO: 19), LCDR2 (SEQ ID NO: 20), and LCDR3 (SEQ ID NO: 21). The recitation is indefinite because it is unclear whether the sequence identifiers (SEQ ID NOs) are required by the claim or merely exemplary. See, MPEP 2173.05(d).
For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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.
Claims 1, 20 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0140491 A1 to Kyratsous et al.
Kyratsous discloses methods for retargeting recombinant viral vectors in vivo by use of a multispecific binding molecule, e.g., a bispecific antibody, that specifically binds to a heterologous epitope displayed by a viral capsid protein and an antigen expressed on the surface of a cell of interest. The recombinant viral capsid exhibits reduced to abolished natural tropism, which is restored and redirected upon combination with the multispecific/bispecific binding molecule, thereby retargeting the viral vector to the cell of interest. See, e.g., Abstract; par. 15-16.
Kyratsous discloses the multispecific/bispecific binding molecule targets a tumor-associated antigen (TAA). See, par. 41-42, 134-136. Kyratsous further provides pharmaceutical compositions comprising the recombinant virus and the multispecific binding molecule, and administration to a subject having cancer. See, e.g., par. 169-172, 184.
Claim 1 further recites that the virus is a herpes simplex virus (HSV). Kyratsous discloses that the recombinant virus may be an adenovirus (Ad) or adeno-associated virus (AAV). See, e.g., par. 67. Kyratsous does not expressly teach applying the disclosed retargeting approach to an HSV, as instantly claimed in claim 1.
However, Kyratsous discloses that other viral retargeting approaches known in the art have been previously applied to HSV, including an approach utilizing an adaptor which recognizes both a wildtype virus surface protein and a target cell. See, par. 4, 10-11, 13. Kyratsous’s approach, by inserting a heterologous epitope into the viral capsid, advantageously reduces or abolishes the virus’s natural tropism and, via an adaptor molecule, redirects the virus to the target cells. See, par. 14-15.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to apply Kyratsous’s retargeting approach to HSV with a reasonable expectation of success because other retargeting approaches have been previously applied to HSV, including an approach utilizing an adaptor which recognizes both a wildtype virus surface protein and a target cell, and Kyratsous’s retargeting approach advantageously reduces or abolishes the virus’s natural tropism and redirects the virus to the target cells.
For these reasons, claim 1 would have been prima facie obvious over the prior art.
Regarding claim 20, Kyratsous discloses that the TAA is PSMA. See, par. 42, 136.
Regarding claim 40, the claim further recites that the method is performed for treating a cancer in a subject in need thereof. Kyratsous provides pharmaceutical compositions comprising the recombinant virus and the multispecific binding molecule, and administration to a subject having cancer. See, e.g., par. 169-172, 184.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0140491 A1 to Kyratsous et al., as applied to claims 1, 20 and 40 above; in further view of Goins et al. (2016) “Retargeting of herpes simplex virus (HSV) vectors” Current opinion in virology, 21, 93-101.
Kyratsous does not teach that heterologous peptide is inserted into or replaces a portion of the wildtype glycoprotein D (gD), as claimed in claim 2.
Goins is relevant prior art for disclosing retargeting of HSV by use of an adaptor which recognizes both a wildtype virus surface protein and a target cell. The adapter protein consists of a portion that binds to an HSV glycoprotein, such as gD, and a second component that binds to a target receptor, such as a receptor on a tumor cell. See, Abstract; pg. 96, col. 2; fig. 3d. The glycoprotein D (gD) is essential for viral entry and retargeting. See, fig. 1-2.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to further modify the invention of Kyratsous by selecting glycoprotein D (gD) as the insertion site for the heterologous peptide, in view of Goins, with a reasonable expectation of success because gD is essential for viral entry and retargeting, and gD has been previously used as a binding site for adapter molecules for retargeting HSV.
For these reasons, claim 2 would have been prima facie obvious over the prior art.
Claims 2, 8, 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0140491 A1 to Kyratsous et al., as applied to claims 1, 20 and 40 above; in further view of Leoni et al. (2017) “A strategy for cultivation of retargeted oncolytic herpes simplex viruses in non-cancer cells” Journal of virology, 91(10), 13 pages.
Kyratsous does not teach that the heterologous peptide is GCN4 or a fragment thereof, as claimed in claims 8 and 10.
Leoni is relevant prior art for disclosing a modified HSV expressing a modified glycoprotein H (gH) containing a GCN4 fragment that can be selectively propagated in Vero cells which express an artificial GCN4-scFv receptor (GCN4R) on its surface, facilitating viral entry and replication. The production of clinical-grade viruses for human therapy should avoid the use of cancer cells, and the Vero-GCN4R cell line provides an efficient system for cultivation of retargeted, oncolytic HSVs in non-cancer cells. Leoni further teaches that modification of both gH and gD is suitable for double retargeting approaches, e.g., where one of the glycoproteins is used for retargeting to cancer cells in vivo and the other glycoprotein is used for retargeting to an in vitro production cell line. See, Abstract; pg. 1-3.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the invention of Kyratsous by selecting GCN4 or a fragment thereof as the heterologous peptide, in view of Leoni, with a reasonable expectation of success because incorporating GCN4 or a fragment as the heterologous peptide would permit the in vitro production of the recombinant viruses in the Vero-GCN4R cell line without the use of cancer cells, which should be avoided in the production of clinical-grade viruses for human therapy.
For these reasons, claims 8 and 10 would have been prima facie obvious over the prior art.
Regarding claim 2, Leoni teaches that modification gH or gD is suitable for retargeting HSV. See, Abstract; pg. 1-3.
Regarding claim 11, Kyratsous discloses that the first binding domain of the bispecific adaptor protein, which targets the heterologous peptide, is a scFv and comprises a complementarity determining region (CDR) that specifically recognizes the heterologous peptide, e.g., a CDR3 region of a heavy and/or light chain variable domain. See, e.g., par. 40, 118.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James D Schultz can be reached at (571)272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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