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 (claims 1-27) and species i) CD19 and CCL5, ii) position 117005 to 132096 in the P prototype genome of F strain, iii) IL-12, and iv) Kymriah® in the reply filed on 4/20/2026 is acknowledged.
Status of the Claims
Claims 28-29 have been withdraw as being directed to a non-elected invention. Claims 15, 19, 24, 26 and 27 have been withdrawn as being directed to a non-elected species. Claims 1-14, 16-18, 20-23 and 25 are under examination at this time.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See, for example, paragraph [0050]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of trademarks has been noted in this application. A trademark should be capitalized wherever it appears and be accompanied by the generic terminology.
Although the use of trademarks is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner, which might adversely affect their validity as trademarks.
Claim Objections
Claims 2-5, 11, 18, 21, 22, 23, and 25 are objected to because of the following informalities:
Claims 2, 3, 5, 18, 22, 23, and 25 should recite “selected from the group consisting of . . .”.
Claim 4 should recite “that has at least 90% amino acid sequence identity to the wild-type extracellular . . .”.
Claim 11 should recite “downstream of the polynucleotide . . .”.
Claim 21 should recite “comprising, separately, the oHSV of claim 1 . . .”.
Appropriate correction is required.
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.
Claims 1-8, 10-14, 16-18, 20-23 and 25 are rejected 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. 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to, inter alia, a truncated nonsignaling variant of at least one tumor associated/specific antigen. Applicant has disclosed four nonsignaling variants of CD19, BCMA, HER2 and Trop-2 (see paragraph [0049] of the instant specification). However, applicant’s claims encompass numerous antigen variants that are nonsignaling and that are structurally and biologically different from CD19, BCMA, HER2 and Trop-2.
The written description rejection is made because the claims are interpreted as being drawn to a genus of truncated nonsignaling variant of at least one tumor associated/specific antigen which lack the function of signaling. The applicable standard for the written description requirement can be found in MPEP 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc., 63 USPQ2d 1609; Vas- Cath Inc. v. Mahurkar, 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004). 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 specification is the structure of four nonsignaling variants of CD19, BCMA, HER2 and Trop-2 at paragraph [0049] of the instant specification. There is no disclosure of sufficient characteristics of the claimed genus to allow persons of ordinary skill in the art to recognize that applicant was in possess of the claimed genus.
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus. A definition by function alone (i.e., nonsignaling) is not sufficient because it is only an indication of what a thing does, rather than what it is. EliLily, 119 F.3 at 1568, 43 USPQ2d at 1406.
The court clearly states in Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, 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 the inventors invented what is claimed. As discussed above, the skilled artisan cannot envision the distinguishing, identifying characteristics of the encompassed genus of truncated nonsignaling variants of at least one tumor associated/specific antigen which lack the function of signaling. Given that the specification has only described four such nonsignaling variants, the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
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 4 and 16 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 4 recites that the non-signaling variant is an extracellular domain. Claim 1, from which claim 4 depends, states that the tumor cell expresses and presents the non-signaling variant as a biomarker. It is not clear how an extracellular domain, which lacks a transmembrane domain, is presented by a tumor cell.
Claim 16 is indefinite because it lacks a reference sequence for the cited positions. Since the nucleic acid positions vary in the different isolates of the HSV P prototype F strain, one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention without a reference sequence. Therefore, a sequence of HSV referred to by SEQ ID NO: should be recited in the claim as a reference for the positions cited the claim.
Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
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.
Claim 13 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 1, from which claim 13 depends, states that the tumor cell expresses and presents the tumor associated/specific antigen. However, claim 13 states that the tumor cell does not express the tumor associated/specific antigen encoded by the polynucleotide.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 factual inquiries 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.
Claim(s) 1, 2, 3, 4, 7, 9, 12, 17, 18 and 21-23 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (Sci Transl Med., September 2020, 12(559):1-29) and further in view of McGrath et al. (Hum Gene Ther, Feb 2021, 32(3-4):150–157).
The instant claims are directed to a genetically modified oncolytic herpes simplex virus (oHSV),wherein the genome of the oHSV is incorporated with a polynucleotide encoding
(a) a truncated nonsignaling variant of at least one tumor associated/specific antigen, and
(b) at least one chemokine,
wherein the expression of the truncated nonsignaling variant and the at least one chemokine is under the control of an immediate-early gene promoter of HSV, and
wherein the truncated nonsignaling variant is expressed and presented on a tumor cell surface as a biomarker upon replication of the oHSV in the tumor cell, and the at least one chemokine is expressed and released to induce chemotaxis of an immune cell towards the tumor cell.
Park et al. discloses the transgene delivery potential of OV to selectively infect and drive tumor-specific expression of a proof-of-concept CAR-targetable tumor antigen, a truncated non-signaling variant of CD19 (CD19t). Park et al. observed that OV armed with CD19t promoted endogenous T cell, as well as CAR T cell, infiltration into tumors. CD19-CAR T cells also induced the release of intact virus from dying tumor cells, a mechanism by which the combination therapy produced effective tumor regression (see page 2). Additionally, Park et al. suggests further modifying the armed OVs to also express checkpoint pathway inhibitors, cytokines, and chemokines to augment CAR T cell trafficking to tumors and their anti-tumor activities (see page 7). Park et al. teaches that OVs such as vaccinia, HSV, Maraba virus and adenovirus can be used (see page 8).
While Park et al. teaches that the OVs can be further modified to express, inter alia, chemokines, Park et al. does not teach that the chemokine is CCL5 (also known as RANTES). McGrath et al. teaches arming oHSV-1 with GM-CSF made the oHSV achieve clinical efficacy against melanoma (see page 152, right column). McGrath et al. also teaches arming oncolytic adenovirus with RANTES and IL-15 led to improved tumor control due to production of both RANTES and IL-15. A similar approach was used with another oncolytic virus (vaccinia) which was armed with the chemokine CXCL11. CXCL11 is another chemokine that attracts effector T cells (see page 153, left column). McGrath et al. also teaches that oncolytic viruses (OVs) armed with the tumor antigen CD19 makes cells that express the CD19 antigen targetable by CD19-specific CAR T cells. However, improved antitumor efficacy was observed when the oncolytic virus was armed with a truncated version of CD191 (see page 155). As for oncolytic viruses, McGrath et al. teaches oHSV-1, Adenovirus, Vaccinia, and VSV.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the CD19t armed OVs taught by Park et al. (e.g., vaccinia, HSV, Maraba virus and adenovirus) and include as the chemokine RANTES (CCL5) or CXCL11 as taught by McGrath et al. One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of McGrath et al. [RANTES and IL-15 led to improved tumor control; CXCL11 is another chemokine that attracts effector T cells].
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
For claim 12, Park et al. teaches treating solid tumors.
For claims 17-18, Park et al. teaches combining RANTES and IL-15. McGrath et al. teaches that TNF-α and IL-2 combined with a CAR T cell specific for mesothelin demonstrated improved tumor control. TNF-α and IL-2 are known to induce production of chemokines such as CXCL10 (see page 153). McGrath et al. also teaches that an OV armed with CD44, IL-12 and PD-L1 was used to boost HER2-specific CAR T cell function (see page 155, right column). Accordingly, it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to also include cytokines such as IL-15, IL-12, TNF-α and IL-2 to induce the production of chemokines that can attract effector T cells or to enhance CAR T cell function as taught by McGrath et al.
For claims 21-23 and 25, the cited prior art teaches that the modified OVs (e.g., HSV expressing CD19t and RANTES) along with antigen specific CAR T cells (e.g., CD19 CAR T cells) are needed to treat a tumor. The cited references do not specifically teach a kit. However, the concept of packaging components into a kit is well known and routine in the art. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to package components into a kit for i) treating a tumor, or ii) performing an assay to determine the effectiveness of a truncated nonsignaling variant of at least one tumor associated/specific antigen, and at least one chemokine. Further, one would be motivated to do this for commercial exploitation of the invention and to provide convenience for the end user.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nicole Kinsey White whose telephone number is (571)272-9943. The examiner can normally be reached M to Th 6:30 am to 6:00 pm.
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, Thomas Visone can be reached at 571-270-0684. 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.
NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
1 McGrath et al. cites Park et al. for the truncated CD19.
Prosecution Insights