Office Action 1: Notice of Allowance (2025-03-12)

CLAIMS:
CLAIMS

What is Claimed is:

Attorney Docket No. 44GC-320421-US2

1\. A genetically modified Herpes Simplex Virus Type 1 (HSV-1), comprising a polynucleotide encoding a Fab of an anti-PD-1 antibody,
wherein the anti-PD-1 antibody comprises a heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 regions, and a light chain variable region comprising light chain CDR1, CDR2, and CDR3 regions, and
wherein the heavy chain CDR1, CDR2, and CDR3 regions and the light chain CDR1, CDR2, and CDR3 regions comprise amino acid sequences set forth in SEQ ID NOs: 1, 2, 3, 34, 35, and 36, respectively.

2\. The genetically modified HSV-1 of claim 1, wherein the heavy chain and the light chain variable regions comprise amino acid sequences having at least 80%, 85%, 90%, 95%, 98% 99% or 100% identity to SEQ ID NOs: 67 and 80, respectively.

3\. The genetically modified HSV-1 of claim 1, wherein the anti-PD-1 antibody comprises a heavy chain constant region having an amino acid sequence having at least 80%, 85%, 90%, 95%, 98% 99% or 100% identity to SEQ ID NOs: 97, 99 or 129, and/or a light chain constant region having an amino acid sequence having at least 80%, 85%, 90%, 95%, 98% 99% or 100% identity to SEQ ID NOs: 98 or 130.

4\. The genetically modified HSV-1 of claim 1, wherein the Fab of an anti-PD-1 antibody comprises a mouse heavy chain variable domain, a human IgG1 CH1 constant domain, a mouse light chain variable domain, and a human kappa light chain constant domain, having sequences set forth in SEQ ID NOs: 67, 99, 80, and 98, respectively.

5\. The genetically modified HSV-1 of claim 1, further comprising a human IL-12 gene.

6\. The genetically modified HSV-1 of claim 1, wherein an inverted repeat region is removed.

7\. The genetically modified HSV-1 of claim 6, wherein the inverted repeat region is replaced by a human IL-12 gene.

8\. The genetically modified HSV-1 of claim 1, wherein the polynucleotide encoding the Fab is inserted between UL3 and UL4.57

OFFICE ACTION:
DETAILED ACTION
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 .
Claim Status
Claims 1-8 are under consideration in this office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has no complied with one or more conditions for receiving benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA  35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62/657,927, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA  35 U.S.C. 112, first paragraph for one or more claims of this application. The virus claimed is not included in the priority document. Accordingly, claims 1-8 are not entitled to the benefit of the prior application. Claims 1-8 are given an earliest effective filing date of April 12, 2019, the filing date of PCT/US2019/027115.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 10, 2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the examiner.
Terminal Disclaimer
The terminal disclaimer filed on February 27, 2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US patent 12,037,395 has been reviewed and is accepted.  The terminal disclaimer has been recorded.
REASONS FOR ALLOWANCE
The following is an examiner’s statement of reasons for allowance: the prior art fails to teach a modified HSV-1 comprising a polynucleotide encoding the Fab of an anti-PD-1 antibody comprised of HCDR1-3 and LCDR 1-3 of SEQ ID NOs: 1, 2, 3, 34, 35, and 36, respectively. The claimed modified virus expresses therapeutic anti-PD-1 antibody for the effective treatment of cancer. It is noted that methods related to generating the HSV-1 virus encoding an anti-PD-1 antibody are well described in the existing art (see US 20190083555, instant PTO-892), and the invention is fully enabled.
The closest prior art is WO-2017058115, published April 6, 2017 (see IDS form 4/10/2024), which teaches anti-PD-1 antibodies (pg 5, ln 15-31). However, it has been determined that the prior art does not teach the amino acid sequences of the anti-PD-1 antibody of the instant claims. The claimed invention is, therefore, free of the prior art.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee.  Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Claims 1-8 are allowed.



CITED REFERENCE SUMMARIES: Ref US20190083555A1: [content unavailable]
Ref US2019027115: Claims:
1. An isolated monoclonal antibody, or an antigen-binding portion thereof, binding to PD-l, comprising a heavy chain variable region comprising a CDR1 region, a CDR2 region and a CDR3 region, wherein the CDR1 region, the CDR2 region and the CDR3 region comprise amino acid sequences set forth in (1) SEQ ID NOs: 1, 2 and 3, respectively; (2) SEQ ID NOs: 4, 5 and 6, respectively; (3) SEQ ID NOs: 7, 8 and 9, respectively; (4) SEQ ID NOs: 10, 11 and 12, respectively; (5) SEQ ID NOs: 13, 14 and 15, respectively; (6) SEQ ID NOs: 16, 17 and 18, respectively; (7) SEQ ID NOs: 19, 20 and 21, respectively; (8) SEQ ID NOs: 22, 23 and 24, respectively; (9) SEQ ID NOs: 25, 26 and 27, respectively; (10) SEQ ID NOs: 28, 29 and 30, respectively; or (11) SEQ ID NOs: 31, 32 and 33, respectively, wherein the antibody or antigen-binding fragment thereof binds PD-l.
2. The antibody, or the antigen-binding portion thereof, of claim 1, comprising a heavy chain variable region comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 98% 99% or 100% identity to SEQ ID NOs: 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78 or 79.
3. The antibody, or the antigen-binding portion thereof, of claim 1, further comprising a light chain variable region comprising a CDR1 region, a CDR2 region and a CDR3 region, wherein the CDR1 region, the CDR2 region and the CDR3 region comprise amino acid sequences of (1) SEQ ID NOs: 34, 35 and 36, respectively; (2) SEQ ID NOs: 37, 38 and 39, respectively; (3) SEQ ID NOs: 40, 41 and 42, respectively; (4) SEQ ID NOs: 43, 44 and 45, respectively; (5) SEQ ID NOs: 46, 47 and 48, respectively; (6) SEQ ID NOs: 49, 50 and 51, respectively; (7) SEQ ID NOs: 52, 53 and 54, respectively; (8) SEQ ID NOs: 55, 56 and 57, respectively; (9) SEQ ID NOs: 58, 59 and 60, respectively; (10) SEQ ID NOs: 61, 62 and 63, respectively; or (11) SEQ ID NOs: 64, 65 and 66, respectively.
4. The antibody, or the antigen-binding portion thereof, of claim 1, further comprising a light chain variable region comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 98% 99% or 100% identity to SEQ ID NO: 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95 or 96.
5. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain and the light chain variable regions comprise amino acid sequences having at least 80%, 85%, 90%, 95%, 98% 99% or 100% identity to (1) SEQ ID NOs: 67 and 80, respectively; (2) SEQ ID NOs: 68 and 81, respectively; (3) SEQ ID NOs: 69 and 81, respectively; (4) SEQ ID NOs: 68 and 82, respectively; (5) SEQ ID NOs: 68 and 83, respectively; (6) SEQ ID NOs: 68 and 84, respectively; (7) SEQ ID NOs: 68 and 85, respectively; (8) SEQ ID NOs: 68 and 86, respectively; (9) SEQ ID NOs: 69 and 86, respectively; (10) SEQ ID NOs: 70 and 87 respectively; (11) SEQ ID NOs: 71 and 88, respectively; (12) SEQ ID NOs: 72 and 89, respectively; (13) SEQ ID NOs: 73 and 90, respectively; (14) SEQ ID NOs: 74 and 91, respectively; (15) SEQ ID NOs: 75 and 92, respectively; (16) SEQ ID NOs: 76 and 93, respectively; (17) SEQ ID NOs: 77 and 94, respectively; (18) SEQ ID NOs: 78 and 95, respectively; or (19) SEQ ID NOs: 79 and 96, respectively.
6. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1, comprising a heavy chain constant region having an amino acid sequence having at least 80%, 85%, 90%, 95%, 98% 99% or 100% identity to SEQ ID NOs: 97, 99 or 129, and/or a light chain constant region having an amino acid sequence having at least 80%, 85%, 90%, 95%, 98% 99% or 100% identity to SEQ ID NOs: 98 or 130.
7. The antibody, or the antigen-binding portion thereof, of claim 1, which (a) binds to human PD-l; (b) binds to monkey PD-l; (c) inhibits binding of PD-L1 to PD-l; (d) increases T cell proliferation; (e) stimulates an immune response; and/or (f) stimulates an antigen-specific T cell response.
8. The antibody, or the antigen-binding portion thereof, of claim 1, which is a mouse, human, chimeric or humanized antibody.
9. The antibody, or the antigen-binding portion thereof, of claim 1, which is an IgGl, IgG2 or IgG4 isotype.
10. A pharmaceutical composition comprising the antibody, or antigen-binding portion thereof, of claim 1, and a pharmaceutically acceptable carrier.
11. The pharmaceutical composition of claim 10, further comprising an anti -tumor agent.
12. A method for inhibiting tumor growth in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 10.
13. The method of claim 12, wherein the tumor is a solid or non-solid tumor.
14. The method of claim 12, wherein the tumor is selected from the group consisting of lymphoma, leukemia, multiple myeloma, melanoma, colon adenocarcinoma, pancreas cancer, colon cancer, gastric intestine cancer, prostate cancer, bladder cancer, kidney cancer, ovary cancer, cervix cancer, breast cancer, lung cancer, renal-cell cancer and nasopharynx cancer.
Ref US12037395: Claims:
1. An isolated monoclonal antibody, or an antigen-binding portion thereof, binding to PD-1, comprising a heavy chain variable region comprising a heavy chain CDR1 region, a heavy chain CDR2 region and a heavy chain CDR3 region, and a light chain variable region comprising a light chain CDR1 region, a light chain CDR2 region and a light chain CDR3 region, wherein the heavy chain CDR1 region, the heavy chain CDR2 region, the heavy chain CDR3 region, the light chain CDR1 region, the light chain CDR2 region and the light chain CDR3 region comprise the amino acid sequences set forth in
(i) SEQ ID NOs: 1, 2, 3, 34, 35, and 36, respectively;
(ii) SEQ ID NOs: 4, 5, 6, 37, 38, and 39, respectively;
(iii) SEQ ID NOs: 7, 8, 9, 40, 41, and 42, respectively;
(iv) SEQ ID NOs: 10, 11, 12, 43, 44, and 45, respectively;
(v) SEQ ID NOs: 13, 14, 15, 46, 47, and 48, respectively;
(vi) SEQ ID NOs: 16, 17, 18, 49, 50, and 51, respectively;
(vii) SEQ ID NOs: 19, 20, 21, 52, 53, and 54, respectively;
(viii) SEQ ID NOs: 22, 23, 24, 55, 56, and 57, respectively;
(ix) SEQ ID NOs: 25, 26, 27, 58, 59, and 60, respectively;
(x) SEQ ID NOs: 28, 29, 30, 61, 62, and 63, respectively; or
(xi) SEQ ID NOs: 31, 32, 33, 64, 65, and 66, respectively.
2. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1, wherein the heavy chain and the light chain variable regions comprise amino acid sequences having at least 80%, 85%, 90%, 95%, 98% 99% or 100% identity to (i) SEQ ID NOs: 67 and 80, respectively; (ii) SEQ ID NOs: 68 and 81, respectively; (iii) SEQ ID NOs: 69 and 81, respectively; (iv) SEQ ID NOs: 68 and 82, respectively; (v) SEQ ID NOs: 68 and 83, respectively; (vi) SEQ ID NOs: 68 and 84, respectively; (vii) SEQ ID NOs: 68 and 85, respectively; (viii) SEQ ID NOs: 68 and 86, respectively; (ix) SEQ ID NOs: 69 and 86, respectively; (x) SEQ ID NOs: 70 and 87 respectively; (xi) SEQ ID NOs: 71 and 88, respectively; (xii) SEQ ID NOs: 72 and 89, respectively; (xiii) SEQ ID NOs: 73 and 90, respectively; (xiv) SEQ ID NOs: 74 and 91, respectively; (xv) SEQ ID NOs: 75 and 92, respectively; (xvi) SEQ ID NOs: 76 and 93, respectively; (xvii) SEQ ID NOs: 77 and 94, respectively; (xviii) SEQ ID NOs: 78 and 95, respectively; or (xix) SEQ ID NOs: 79 and 96, respectively.
3. The isolated monoclonal antibody, or an antigen-binding portion thereof, of claim 1, wherein the heavy chain constant region comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98% 99% or 100% identity to SEQ ID NOs: 97, 99 or 129, and/or the light chain constant region comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 98% 99% or 100% identity to SEQ ID NOs: 98 or 130.
4. The antibody, or the antigen-binding portion thereof, of claim 1, which (a) binds to human PD-1; (b) binds to monkey PD-1; (c) inhibits binding of PD-L1 to PD-1; (d) increases T cell proliferation; (e) stimulates an immune response; and/or (f) stimulates an antigen-specific T cell response.
5. The antibody, or the antigen-binding portion thereof, of claim 1, which is a mouse, chimeric or humanized antibody.
6. The antibody, or the antigen-binding portion thereof, of claim 1, which is an IgG4 IgG1, IgG2 or IgG4 isotype.
7. A pharmaceutical composition comprising the antibody, or antigen-binding portion thereof, of claim 1, and a pharmaceutically acceptable carrier.
8. A method for inhibiting tumor growth in a subject, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 7.
9. The method of claim 8, wherein the tumor is a solid or non-solid tumor.
10. The method of claim 8, wherein the tumor is selected from the group consisting of lymphoma, leukemia, multiple myeloma, melanoma, colon adenocarcinoma, pancreas cancer, colon cancer, gastric intestine cancer, prostate cancer, bladder cancer, kidney cancer, ovary cancer, cervix cancer, breast cancer, lung cancer, renal-cell cancer and nasopharynx cancer.
Ref US20190083555: Claims:
1. A modified Herpes Simplex Virus type 1 (HSV-1) capable of acting as a vector of cellular and or viral genes comprising a modified HSV-1 genome wherein the modification comprises a deletion between the promoter of UL56 gene and the promoter of US1 gene of a wild-type HSV-1 genome such that (i) one copy of all double-copy genes is absent and (ii) sequences required for expression of all existing open reading frames (ORFs) in the viral DNA after the deletion are intact.
2. The modified HSV-1 according to claim 1, wherein the double-copy genes comprise genes encoding ICP0, ICP4, ICP34.5, ORF P and ORF O and duplicated non-coding sequences interspaced between the deleted region.
3. The modified HSV-1 according to claim 1, wherein the HSV-1 has a genome isomer of prototype (P).
4. The modified HSV-1 according to claim 1, wherein the HSV-1 is selected from strains any existing HSV isolate including strains F, KOS, and 17.
5. The modified HSV-1 according to claim 3, wherein the deletion causes excision of nucleotide positions 117005 to 132096 in the genome of F strain.
6. A recombinant oncolytic Herpes Simplex Virus type 1 (HSV-1) comprising a modified HSV-1 virus capable of acting as a vector of cellular and or viral genes wherein the modification comprises a deletion between the promoter of UL56 and the promoter of US1 of a wild-type HSV-1 genome such that (i) one copy of all double-copy genes is absent and (ii) sequences required for expression of all existing open reading frames (ORFs) in the viral DNA after the deletion are intact; and
a heterologous nucleic acid sequence encoding an immunostimulatory and/or immunotherapeutic agent, wherein the heterologous nucleic acid sequence is stably incorporated into at least the deleted region of the modified HSV-1 genome.
7. The recombinant oncolytic HSV-1 according to claim 6, wherein the immunostimulatory agent is selected from GM-CSF, IL 2, IL 5, IL 12, IL 15, IL 24 and IL 27.
8. The recombinant oncolytic HSV-1 according to claim 6, wherein the immunotherapeutic agent is selected from an anti-PD-1 agent and an anti-CTLA-4 agent.
9. The recombinant oncolytic HSV-1 according to claim 6, wherein the recombinant oncolytic HSV-1 comprises a heterologous nucleic acid sequence encoding IL-12, an anti-PD-1 agent and/or an anti-CTLA-4 agent.
10. (canceled)
11. (canceled)
12. The recombinant oncolytic HSV-1 according to claim 6, wherein the recombinant oncolytic HSV-1 comprises a first heterologous nucleic acid sequence encoding IL-12 and a second heterologous nucleic acid sequence encoding an anti-PD agent or an anti-CTLA-4 agent.
13. (canceled)
14. The recombinant oncolytic HSV-1 according to claim 6, wherein the recombinant oncolytic HSV-1 comprises a first heterologous nucleic acid sequence encoding an anti-PD-1 agent and a second heterologous nucleic acid sequence encoding an anti-CTLA-4 agent.
15. The recombinant oncolytic HSV-1 according to claim 6, wherein the recombinant oncolytic HSV-1 comprises a first heterologous nucleic acid sequence encoding IL-12, a second heterologous nucleic acid sequence encoding an anti-PD-1 agent, and a third heterologous nucleic acid sequence encoding an anti-CTLA-4 agent.
16. The recombinant oncolytic HSV-1 according to claim 6, wherein the recombinant oncolytic HSV-1 further comprises a promoter sequence operably linked to the heterologous nucleic acid sequence.
17. The recombinant oncolytic HSV-1 according to claim 12, wherein the first heterologous nucleic acid sequence is inserted into the deleted region of the modified HSV-1 genome, and the second heterologous nucleic acid sequence is inserted between UL3 to UL4 genes in the UL component of the modified HSV-1 genome.
18. (canceled)
19. The recombinant oncolytic HSV-1 according to claim 14, wherein the first heterologous nucleic acid sequence is inserted into the deleted region of the modified HSV-1 genome, and the second heterologous nucleic acid sequence is inserted between UL3 to UL4 genes in the UL component of the modified HSV-1 genome.
20. The recombinant oncolytic HSV-1 according to claim 15, wherein the first heterologous nucleic acid sequence is inserted into the deleted region of the modified HSV-1 genome, the second heterologous nucleic acid sequence is inserted between UL3 to UL4 genes in the UL component of the modified HSV-1 genome, and the third heterologous nucleic acid sequence is inserted between UL37 to UL38 genes in the UL component of the modified HSV-1 genome.
21. The recombinant oncolytic HSV-1 according to claim 15, wherein the first heterologous nucleic acid sequence is inserted into the deleted region of the modified HSV-1 genome, the second heterologous nucleic acid sequence is inserted between UL37 to UL38 genes in the UL component of the modified HSV-1 genome, and the third heterologous nucleic acid sequence is inserted between UL3 to UL4 genes in the UL component of the modified HSV-1 genome.
18. The recombinant oncolytic HSV-1 according to claim 13, wherein the promoter sequence is a CMV promoter or an Egr promoter.
19. The recombinant oncolytic HSV-1 according to claim 6, wherein the immunostimulatory and/or immunotherapeutic agent is humanized.
20. The recombinant oncolytic HSV-1 according to claim 8, wherein the anti-PD-1 agent or anti-CTLA-4 agent contains an antibody variable region providing for specific binding to a PD-1 or CTLA-4 epitope, respectively.
25. The recombinant oncolytic HSV-1 according to claim 24, wherein the antibody variable region is a complete antibody, an antibody fragment or a recombinant derivative of an antibody or antibody fragment.
26. A pharmaceutical composition comprising an effective amount of the recombinant oncolytic HSV-1 of claim 1 and a pharmaceutically acceptable carrier.
27. The pharmaceutical composition according to claim 26, wherein the composition is formulated for intratumoral administration.
28. A method of treating or alleviating a cancer comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of claim 26.
29. The method according to claim 28, wherein a second therapy is administered to the subject before, at the same time, or after the pharmaceutical composition is administered.
30. The method according to claim 29, wherein the second therapy is selected from chemotherapeutic, radiotherapeutic, immunotherapeutic or surgery intervention.
31. The method according to claim 28, wherein the subject is a human being.
32. The method according to claim 28, wherein the cancer is selected from esophageal cancer, lung cancer, prostate cancer, and bladder cancer.
Ref APP62657927: [content unavailable]