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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 4/13/2026 is acknowledged.
Claims 4, 9-11, 14-15,22,23,35-42,50 and 52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 4/13/2026. Claims 4 and 9-11, 14-15 are withdrawn as they fail to relate to the elected SEQ ID NO:34.
Applicant elected SEQ ID NO:34 and amended the claims to recite SEQ ID NO:36. Because the art of record (WO2021259508; Sapreme) taught SEQ ID NO:34 and the additional anti- CTLA-4 sequence that is part of SEQ ID NO:36, it is deemed to present no undue burden, the restriction requirement between these two species, SEQ ID NO:34 and 36, is withdrawn.
Claim Interpretation
The claims are drawn to an “armed” Seneca Valley virus comprising a Seneca Valley Viruse and a nucleic acid encoding a therapeutic protein. Given the definition of “armed Seneca Valley Virus” at para 78, the claims are interpreted as a SVV with the nucleic acid encoding a therapeutic protein inserted within the SVV genome.
[0078] As used herein, the phrases "armed Seneca Valley Virus" or "armed SVV" encompass a "Seneca Valley Virus" or "SVV" as defined above, that has been modified to express an agent that is useful for treating cancer. An armed SVV encodes an agent useful for treating cancer. An armed SVV has been engineered to express therapeutic genes
Claim Rejections - 35 USC § 112
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.
The rejection of claims 8,12,20 and 21 under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement is withdrawn in light of the amendments to the claims as the claims are no longer directed to variants of SEQ ID NO:34. However, similar grounds of rejection are set forth below with regard to SEQ ID NO:36.
Claims 1,5-6,8,12,,17-21 and 43 are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The specification has described the nucleotide sequences set forth by SEQ ID NO:35, encoding SEQ ID NO:36. The specification, however, has not described any variant sequences of those nucleotide sequences that are within the genus of variants that include sequences having at least 85% identity to the nucleic acid sequence of SEQ ID NO:35 or encoding a protein having an amino acid sequence set forth by SEQ ID NO:36and have ability to bind PDL-1 and CTLA-4.
In the instant case the PD-L1+CTLA-4 nanobody variants encompassed by the claims lack a written description. The specification fails to describe what amino acid sequences fall into this genus and it was unknown as of Applicants’ effective filing date that any of these proteins would have the same structural and functional properties as the protein whose sequence is set forth by SEQ ID NO:36. There is no evidence on the record of a relationship between the structure anti-PD-L1+CTLA-4 nanobody variants and the amino acid sequence set forth by SEQ ID NO:36 that would provide any reliable information about the structure of proteins within the genus that have the same effect.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the only factor present in the claims is a reference to structure in the form of a recitation of partial structural similarity, “fragment”, or vague structural resemblance. There is not even identification of any particular portion of the structure that must be conserved. The specification does not provide a complete structure of those nucleotide sequences that are fragments and variants of SEQ ID NO:35 or amino acid sequences that are fragments or variants of SEQ ID NO:36, and fails to provide a representative number of species for the encompassed genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the recited genus.
The skilled artisan cannot envision the detailed chemical structure of all of the fragments, derivatives or variants, that are encompassed by the claims, and therefore, conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method. Adequate written description requires more than a mere statement that it is part of the invention, and a reference to a potential method of isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Cir. 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991).
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481, 1483. In Fiddes, claims directed to mammalian FGFs were found to be unpatentable due to lack of written description for that broad class. The specification only provided the bovine sequence.
Applicant is reminded that Vas-Cath makes clear that the written description of 35 U.S.C. 112 is severable from its enablement provision [see p. 1115].
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.
The previous rejection of claims 19-21 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in light of the amendments to the claims.
Claims 1,5-8,12,17-21 and 48 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention
Claim 5 requires the nucleic acid encoding the SVV comprise the nucleic acid encoding the nanobody. This infers that the nucleic acids could be separate and multiple nucleic acids are, therefore, present in the SVV of claim 1. This is unclear as SVV is a non-segmented virus, meaning its genome is a single nucleic acid molecule (see Hawko, Vet. Sci. 2022, 9, 495. https://doi.org/10.3390/vetsci9090495 , specifically page 3). Thus, claims 1 and 5 are unclear as are dependent claims 6-8,12,17-21 and 48.
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.
The rejection of claim 16 under 35 U.S.C. 112(d) is rendered moot by the cancelation of the claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The rejection of claim(s) 1-3,5,13,16-18,43-45 rejected under 35 U.S.C. 102a1 and a2 as being anticipated by US 2020/0197457 (Transgene) is withdrawn as Transgene did not teach the now-recited SEQ ID NO:36.
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 previous rejection of claim(s) 1, and 5-8 under 35 U.S.C. 103 as being unpatentable over US 2020/0197457 (Transgene) in view of WO2021259508 (Sapreme) is withdrawn as the claims are no longer drawn to SEQ ID NO:34, anti-PDL1 nanobody.
Claim(s) 1, 5-8,13,17-18 and 43 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0197457 (Transgene) and Chae (Journal for ImmunoTherapy of Cancer (2018) 6:39 https://doi.org/10.1186/s40425-018-0349-3) in view of WO2021259508 (Sapreme).
Claim 1 is drawn to an armed Seneca Valley Virus comprising a Seneca Valley Virus and a nucleic acid encoding anti-PD-L1+CTLA-4 nanobody and SEQ ID NO:36.
Transgene teaches a Seneca Valley Virus (para 42,44) encoding a dAb (nanobody, para 74,79) directed against PD-L1 and CTLA-4 (para 16 and 91).
Paragraph 16 states, “In one embodiment, the encoded one or more immune checkpoint modulator(s) is an antagonist molecule that antagonizes the activity of PD-1, PD-L1 or CTLA4 with a specific preference for an anti PD-1 antibody and/or an anti CTLA4 antibody.”
Paragraph 91 states, “The present invention encompasses an oncolytic virus encoding more than one immune checkpoint modulator. A preferred example includes without limitation expression of an anti-CTLA-4 antibody and an anti-PD-1 antibody.”
Transgene taught cloning of oncolytic viruses into a plasmid vector (para 27,169-170; claims 17-18). Transgene teaches the vector is NTX-010, which is SVV-001 (claim 13). Transgene teaches that virus can be a pharmaceutical composition comprising a pharmaceutically acceptable vehicle (para. 1, claim 43).
Additionally, Chae provides a detailed review of numerous clinical trials that combine various anti-CTLA-4 and anti_PDL1 treatments.
While Transgene teaches a Seneca Valley Virus encoding a PD-L1+CTLA-4 nanobody, it does not teach the nucleic acid sequence encoding the nanobody or the amino acid sequence of the nanobody.
Claims 1 and 6-8, now limits the nucleic acid sequence encoding an anti-PDL-1+CTLA-4 nanobody to that encoding SEQ ID NO:36 (and up to 10% variants thereof for claims 1,5 and 8) and claim 6 limits the nucleic acid sequence to the sequence set forth by SEQ ID NO:35. Claim 8 limits the nucleic to encoding a protein at least 85% identical to SEQ ID NO:34.
Sapreme teaches the sequence set forth in SEQ ID NO:24 and 32 that are identical to the CTLA-4 and PDL-1 nanobody sequences set forth in the claimed SEQ ID NO:36. Sapreme teaches the PD-L1 sdAb B1 and the CTLA-4 sdAb NB16. Sapreme teaches CTLA-4 and PD-L1 as proteins present on tumor cells and are targets for nanobody (sdAb) therapy. Sapreme provides SEQ ID NO:23 as the nucleic acid encoding SEQ ID NO:24 (which is the anti-CTLA-4 part of SEQ ID NO:36 of the instant invention). Sapreme provides SEQ ID NO:29 as the nucleic acid encoding SEQ ID NO:3o (which is the CTLA-4 portion of SEQ ID NO:36 of the instant invention).
The alignment of SEQ ID NO:31 of Sapreme and the amino acid sequence of the PD-L1 nanobody (SEQ ID NO:34) is set forth below:
PNG
media_image1.png
531
664
media_image1.png
Greyscale
The alignment of SEQ ID NO:23 of Sapreme and the amino acid sequence of the CTLA-4 nanobody (portion of SEQ ID NO:36) is set forth below:
PNG
media_image2.png
480
648
media_image2.png
Greyscale
It would have been obvious at the time of filing, when carrying out the invention of Transgene to combine treatments targeting PDL1 and CTLA4 as taught to be common in the clinical setting by Chae, to turn to Sapreme for the provision of the PD-L1+CTLA-4 nanobody amino acid sequences to generate a nucleic acid sequence that encodes PD-L1 for delivery to tumor cells. One would have been motivated to use the sequence of Sapreme as Sapreme discusses the use of the PD-L1 sdAb B1 in treating tumor cells. One would have had a reasonable expectation of success in combining the teachings as it was routine in the art to back translate protein sequences into nucleic acids to place them into a nucleic acid vector.
With regard to claim 6, while Sapreme teaches SEQ ID NO:31 as encoding SEQ ID NO:32, which is identical to SEQ ID NO:34 of the instant invention and the PDL-1 portion of now-claimed SEQ ID NO:36, Sapreme SEQ ID NO:31 is not identical to the sequence set forth by SEQ ID NO:33 of the instant invention (claim 6; 279/378 nucleotides match, 73.8%). However, SEQ ID NO:31 of Sapreme and SEQ ID NO:33 of the instant invention, encode the same protein and it would be a matter of design choice to use the degeneracy of the genetic code to obtain SEQ ID NO:33 given SEQ ID NO:31 of Sapreme. With regard to the CTLA-4 nanobody portion of SEQ ID NO:35 (encoding SEQ ID NO:36), Sapreme taught SEQ ID NO:23, encoding SEQ ID NO:24. While the nucleic acid sequences are not identical, they encode the same nanobody protein sequence and it would be a matter of design choice to use the degeneracy of the genetic code to obtain SEQ ID NO:35 given SEQ ID NO:23 and 31 of Sapreme.
The rejection of claim(s) 12,18-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0197457 (Transgene; IDS) in view of WO2021259506 (Sapreme) as applied to claims 1 and 5 above, and further in view of Poirer (2012, Journal of General Virology, Volume 93 Issue 12 e00576-19, 13 pages; IDS) is withdrawn.
Claim(s) 12,18-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0197457 (Transgene; IDS) and Chae (Journal for ImmunoTherapy of Cancer (2018) 6:39 https://doi.org/10.1186/s40425-018-0349-3) in view of WO2021259506 (Sapreme) as applied to claims 1, 5-8,13,17-18 and 43 above, and further in view of Poirer (2012, Journal of General Virology, Volume 93 Issue 12 e00576-19, 13 pages; IDS).
Claim 12 limits the virus of claim 5 to comprising a nucleic acid encoding SEQ ID NO:36, which is taught by Transgene and Sapreme (see above), wherein the nucleic acid encoding the therapeutic protein (SEQ ID NO:34) is inserted between the 2A and 2B gene. In teaching a SVV encoding a PD-L1+CTLA-4 nanobody, Transgene does not discuss where to insert the coding sequence within the SVV genome.
However, Poirer taught insertion of a GFP gene in the SVV-001 genome between the 2A and 2B genes in plasmid pNTX-09 to generate pNTX-11, which is the plasmid used in the instant invention (see para 216). Poirer taught how to insert an exogenous coding sequence while retaining native coding sequences of all SVV-001 proteins.
It would have been obvious at the time of filing to insert the nucleic acid encoding the nanobody in to the SVV genome as taught by Transgene between the 2A and 2B genes as taught by Poirer to arrive at the invention as claimed. One would have been motivated to use the insertion site taught by Poirer because the cloning site was provided and known to result in a replication competent virus that did not lose the insertion with passage. One would have had a reasonable expectation of success in making the combination as replacing a nucleic acid insertion in a vector was well with the skill of the ordinary artisan.
With regard to claims 19-21, SEQ ID NO:55 is a plasmid NTX-11 comprising SEQ ID NO:34 at site between the 2A and 2B genes. By inserting the cDNA encoding the anto-PDL1+CTLA-4 nanobody of Transgene and Sapreme in this site of NTX-11 as taught by Poirer, SEQ ID NO:55 is inherently derived.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VALARIE BERTOGLIO whose telephone number is (571)272-0725. The examiner can normally be reached M-F 6AM-2:30PM.
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, Peter Paras can be reached at 571-272-4517. 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.
VALARIE E. BERTOGLIO, Ph.D.
Examiner
Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
Prosecution Insights