DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Applicant's amendments filed 1/29/2026 to claims 1, 20, 24, 26, 41, and 96 have been entered. Claims 2-19, 22, 23, 25, 29-40, 42-95, and 97-100 are canceled. Claims 101 has been added. Claims 1, 20, 21, 24, 26-28, 41, 96, and 101 remain pending, and are being considered on their merits. No claims are withdrawn from consideration at this time. References not included with this Office action can be found in a prior action.
The instant amendments to claims 21, 24, 26, and 96 have overcome the 35 U.S.C. § 112(b) and 112(d) rejections of record, which are withdrawn.
The instant amendments to claim 1 have overcome the 35 U.S.C. § 101, the alternate 35 U.S.C. § 102 and 103, the 35 U.S.C. § 103, and nonstatutory double patenting rejections of record. Modified grounds of rejection are set forth below necessitated by the instant claim amendments.
Any rejections of record not particularly addressed below are withdrawn in light of the claim amendments and/or applicant’s comments.
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 21 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 21 is rejected as indefinite, because the claim now lacks a conjunction between elements ii) and iii) and so it is unclear if elements i)-iii) are alternatives or all are required by the broadest reasonable interpretation of the scope of the claim. Correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 20, 21, 24, 26-28, 41, 96, and 101 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more.
Claim 1 recites a composition comprising a polyclonal population of virus-specific T cells/lymphocytes reactive against one or more SARS-CoV2 antigen, which is directed towards a natural product which lacks any markedly different characteristic towards its nearest natural counterpart. T cells are inherently polyclonal as T cell receptor (TCR) diversity as is generated by the random and imprecise rearrangements of the V and J segments of the TCR alpha (TCRA) and V, D, and J segments of the TCR beta (TCRB) genes in the thymus in vivo as taught by Qi et al. (PNAS (2014), 111(36), 13139-13144) (see the first paragraph in the left column and under the bolded Abstract), and so the ability of endogenous polyclonal T cells to be specifically reactive to structural and non-structural antigens of SARS-CoV2 is simply the natural and inherent immunological reaction to SARS-CoV2 in infected subjects. For example, see the teachings of Xu et al. (BMJ (Feb 2020), 368:m606, 7 pages) for COVID-19 (i.e. SARS-CoV2) infection in human subjects and before the effective filing date of the instant application (see the Abstract and Table 2 of Xu, and the post-filed teachings of Sekine et al. (Cell (Oct 2020), 183, 158-168) who shows that human CD4+ and CD8+ T cells are inherently reactive against the spike (S), membrane (M; i.e. synonymous for Matrix protein as set forth in ¶0071 of the specification), and nucleocapsid antigens (N) (e.g. structural antigens) (Fig. 2C and legend and the paragraph spanning p160-161; e3 for human subjects). Regarding claim 1, T cells inherently express αβ T cell receptors as evidenced by Janeway et al. ( Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; (2001), NCBI Bookshelf reprint of Ch. 3, “Antigen recognition by T cells.”;) (See the 1st paragraph under subheading 3-10 on the first page), and the post-filed teachings of Sekine inherently shows that human CD4+ and CD8+ T cells specific against SARS-CoV2 are Th1 polarized and comprise memory cells (Abstract; p161, right column, paragraph starting “To access the functional capabilities..” and Fig. 3B, 3C, and 3D), and the post-filed evidentiary teachings of Rowntree (PNAS (2024), 121(39), e2411428121; Reference U) makes clear that SARS-CoV2 infection in humans inherently yields a subset of effector T cells (p2, left column, paragraph starting “Introduction to COVID-19 vaccines…”).
Regarding the non-structural antigens of claim 1 and claim 24, polyclonal CD4+ T cells are inherently reactive to nsp4, nsp6, and nsp14 from SARS-CoV2 and polyclonal CD8+ T cells are inherently reactive to nsp6 as set forth by Grifoni et al. (Cell (June 2020), 181(7), 1489-1501.e15; Reference U2). See Grifoni at page 1495, the left column, paragraph starting “In the case for CD4+ T cell responses…” and the paragraph spanning pages 1495-1496 and e3 for human subjects.
Regarding the product-by-process limitations towards ex vivo expansion of the polyclonal T cells of claim 1 and 101, the analysis turns on whether the nature-based product in the claim has markedly different characteristics from its naturally occurring counterpart. See M.P.E.P. § 2106.04(c) and 2113. In this case, there is no evidence of record that the claimed polyclonal T cells possess any markedly different characteristic as compared to the human polyclonal T cells of Xu as evidenced by Sekine, Rowntree, Janeway, and Grifoni.
Alternatively regarding claim 1, the claims does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the product-by-process limitations towards ex vivo expansion of the polyclonal T cells to generate virus-specific T cells is routine and conventional in this art. For example, see the teachings of Leen et al. (WO 2011/028531; provided in the IDS dated 9/16/2022) (see the paragraph starting “In certain embodiments…” on page 5, wherein “CTL” is an acronym for “cytotoxic T lymphocytes/cells as set forth in the paragraph spanning pages 1-2). Alternatively regarding claim 101, ex vivo culturing of T cells with IL-4 and/or IL-4 is routine and conventional in this art over Vella et al. (J Exp Med (1997), 186(2), 325-330; Reference V), who teaches that culturing T cels in vitro with IL-4 and/or IL-7 improves the survival of T cells (Abstract, and Fig. 1).
Regarding claim 20, polyclonal CD4+ and CD8+ T cells/lymphocytes are reactive against one or more SARS-CoV2 antigen are inherent to SARS-CoV2 infection as set forth by Xu as evidenced by Sekine above.
Regarding claims 26-28 and 96, Sekine teaches that CD4+ and CD8+ T cells are inherently reactive against the spike (S), membrane (M; i.e. synonymous for Matrix protein as set forth in ¶0071 of the specification), and nucleocapsid antigens (N) as set forth above, and Grifoni teaches that polyclonal CD4+ T cells are inherently reactive to nsp4, nsp6, and nsp14 from SARS-CoV2 and polyclonal CD8+ T cells are inherently reactive to nsp6 as set forth above.
While Sekine, Rowntree and Grifoni are post-filed art, inherent features need not be recognized at the relevant time but only that the subject matter is inherent in the prior art reference, see M.P.E.P. § 2112 (II). Therefore, the polyclonal T cells of Xu and available before the effective filing date of the instant application as evidenced by Sekine, Janeway, Rowntree, and Grifoni inherently meet the composition and natural product of claims 1, 20, 21, 24, 26-28, 96, and 101 and there is no evidence of record that the claimed polyclonal T cells possess any markedly different characteristic as compared to the polyclonal T cells of Xu as evidenced by Sekine, Janeway, Rowntree, and Grifoni.
Regarding the “upon exposure” of claim 1, claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure; see M.P.E.P. § 2111.02 and 2111.04. In this case, “upon exposure” is analogous to a wherein clause and recited an intended use of the claimed composition, and so has been fully considered but is not afforded any patentable weight as the T cell composition of Xu is reasonably presumed to be inherently capable of meeting the claimed intended use. Also see M.P.E.P. § 2112.
Regarding claims 1, 20, 24, 26-28, and 96, the judicial exception is not integrated into a practical application because the claims are only directed towards a natural product and there is no evidence of record that the claimed polyclonal T cells possess any markedly different characteristic as compared to the polyclonal T cells of Xu as evidenced by Sekine, Janeway, and Grifoni as set forth above.
Furthermore, the broadest reasonable interpretation of the polyclonal T cells of claims 1, 20, 21, 24, 26-28, 96, and 101 necessarily reads on humans per se and is expressly prohibited from being patented under The Leahy-Smith America Invents Act (AIA ), Public Law 112-29, sec. 33, 125 Stat. 284 (September 16, 2011). See M.P.E.P. § 2106 (I) and 2111.
Regarding claim 41, the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the further formulation of the polyclonal T cells of claim 1 for intravenous delivery, wherein the composition is negative for bacteria and fungi for at least 7 days in culture; exhibit less than 5 EU/ml of endotoxin, and is negative for mycoplasma is routine and conventional over Leen et al. (WO 2011/028531; provided in the IDS dated 9/16/2022). See Leen at ¶0159-0160 on page 44.
For the reasons given above, claims 1, 20, 21, 24, 26-28, 41, 96, and 101 are rejected as patent ineligible under 35 U.S.C. § 101.
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 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.
Claims 1, 20, 21, 24, 26-28, 96, and 101 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Xu et al. (BMJ (Feb 2020), 368:m606, 7 pages) as evidenced by Qi et al. (PNAS (2014), 111(36), 13139-13144), Sekine et al. (Cell (Oct 2020), 183, 158-168), Janeway et al. (Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; (2001), NCBI Bookshelf reprint of Ch. 3, “Antigen recognition by T cells.”), Rowntree et al. (PNAS (2024), 121(39), e2411428121; Reference U), and Grifoni et al. (Cell (June 2020), 181(7), 1489-1501.e15).
Xu teaches a composition comprising T cells/lymphocytes in human subjects suffering from SARS-CoV2 infection (Abstract and Table 2), anticipating or reading on claim 1.
Regarding claim 1, Xu is silent of the T Cells are polyclonal. However, Qi teaches that T cells are inherently polyclonal as T cell receptor (TCR) diversity as is generated by the random and imprecise rearrangements of the V and J segments of the TCR alpha (TCRA) and V, D, and J segments of the TCR beta (TCRB) genes in the thymus (see the first paragraph in the left column and under the bolded Abstract). Therefore, Xu as evidenced by Qi anticipates or reads on claim 1.
Regarding claim 1, Xu as evidenced by Qi is silent if the polyclonal T cells in the human subjects infected with SARS-CoV2 are reactive against at least one structural antigen and at least one non-structural antigen. Regarding claim 1, Xu is silent regarding Th1 polarization and memory and effector T cells. Regarding claim 20, Xu is silent if the T cells are CD4+ and CD8+.
Regarding the non-structural antigens of claim 1 and claim 24, human polyclonal CD4+ T cells are inherently reactive to nsp4, nsp6, and nsp14 from SARS-CoV2 and polyclonal CD8+ T cells are inherently reactive to nsp6 as set forth by Grifoni (page 1495, the left column, paragraph starting “In the case for CD4+ T cell responses…” and the paragraph spanning pages 1495-1496; e3 for human subjects).
Regarding claim 1, Sekine inherently shows that human CD4+ and CD8+ T cells specific against SARS-CoV2 are Th1 polarized and comprise memory cells (Abstract; p161, right column, paragraph starting “To access the functional capabilities..” and Fig. 3B, 3C, and 3D).
Regarding claim 1, Rowntree teaches that SARS-CoV2 infection in humans inherently yields a subset of effector T cells (p2, left column, paragraph starting “Introduction to COVID-19 vaccines…”).
Regarding claim 1, T cells inherently express αβ T cell receptors as evidenced by Janeway et al. ( Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; (2001), NCBI Bookshelf reprint of Ch. 3, “Antigen recognition by T cells.”). See the 1st paragraph under subheading 3-10 on the first page.
Regarding claim 20, Sekine teaches that human CD4+ and CD8+ T cells are inherently reactive against the spike (S), membrane (M; i.e. synonymous for Matrix protein as set forth in ¶0071 of the specification), and nucleocapsid antigens (N) (e.g. structural antigens) (Fig. 2C and legend and the paragraph spanning p160-161; e3 for human subjects).
Regarding claims 26-28, and 96, Sekine teaches that CD4+ and CD8+ T cells are inherently reactive against the spike (S), membrane (M; i.e. synonymous for Matrix protein as set forth in ¶0071 of the specification), and nucleocapsid antigens (N) (e.g. structural antigens) as set forth above, and Grifoni teaches that polyclonal CD4+ T cells are inherently reactive to nsp4, nsp6, and nsp14 from SARS-CoV2 and polyclonal CD8+ T cells are inherently reactive to nsp6 as set forth above (e.g. non-structural antigens).
While Sekine, Rowntree, and Grifoni are post-filed art, inherent features need not be recognized at the relevant time but only that the subject matter is inherent in the prior art reference, see M.P.E.P. § 2112 (II). Therefore, the human polyclonal T cells of Xu and available before the effective filing date of the instant application as evidenced by Qi, Sekine, Rowntree, and Grifoni inherently anticipate or read on the composition of claims 1, 20, 24, 26-28, and 96.
Regarding the “upon exposure” of claim 1, claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure; see M.P.E.P. § 2111.02 and 2111.04. In this case, “upon exposure” is analogous to a wherein clause and recited an intended use of the claimed composition, and so has been fully considered but is not afforded any patentable weight as the T cell composition of Xu is reasonably presumed to be inherently capable of meeting the claimed intended use. Also see M.P.E.P. § 2112.
Claims 1 and 101 are product-by-process claims, reciting process limitations towards ex vivo expansion; claims 20, 21, 24, 26-28, and 96 depend from claim 1. See M.P.E.P. § 2113; product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. Furthermore, alternate grounds of rejection under both 102 and 103 is permissible given the lack of physical description of product-by-process claims and the inability of the USPTO to manufacture and compare products. See M.P.E.P. § 2113 (III). Once a product appearing to be substantially identical is found and an art rejection made, the burden shifts to the applicant to show an unobvious difference. In this case, the burden is shifted to Applicant to show that the manufacturing process steps of the product-by-process claims impart any novel and/or non-obvious structural characteristics to the claimed product as compared to the polyclonal T cell composition of Xu as evidenced by Qi which is inherently reactive to at least one structural antigen and at least one non-structural antigen as evidenced by Sekine, Rowntree, and Grifoni. Particularly, if the product-by process limitations of claim 1 does not impart any structural difference then the claims are anticipated. If the product-by process limitations of claim 1 does impart a structural difference, then Applicant must clearly set forth why any structural difference between the claimed composition and the composition of Xu as evidenced by Qi, Sekine, and Grifoni is non-obvious.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Xu as evidenced by Qi, Sekine, Janeway, Rowntree, and Grifoni as applied to claim 1 above, and further in view of Leen et al. (WO 2011/028531; provided in the IDS dated 9/16/2022).
The teachings of Xu as evidenced by Qi, Sekine, Janeway, Rowntree, and Grifoni are relied upon as set forth above.
Regarding claim 41, Xu does not teach the polyclonal T cell composition of claim 1 further formulated for intravenous delivery, wherein the composition is negative for bacteria and fungi for at least 7 days in culture; exhibit less than 5 EU/ml of endotoxin, and is negative for mycoplasma.
Leen teaches methods and compositions for the generation and use of polyclonal cytotoxic T lymphocytes/cells (CTLs) that target multiple viruses and for administration to subjects in need of treatment thereof for infection (Abstract; the last paragraph on page 5 through the first paragraph on page 6; ¶0219), reading in-part on claim 41. Leen teaches the CTLs target at least one antigen from two or more viruses and including Coronavirus (¶0007), reading on claim 41. Leen teaches that criteria for administering the virus-specific CTLs includes negative culture for bacteria and fungi for at least 7 days in culture; exhibit less than 5 EU/ml of endotoxin, and negative for mycoplasma. (¶0159 on page 44), reading on claim 41. Leen teaches administering multivirus-specific T cells by intravenous injection (¶0160 on page 44), reading on claim 41.
Regarding claim 41, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further formulate the polyclonal T cells of Xu as evidenced by Qi and specific for SARS-CoV2 structural and non-structural antigens as evidenced by Sekine and Grifoni for intravenous administration, negative for bacteria and fungi for at least 7 days in culture; exhibit less than 5 EU/ml of endotoxin, and negative for mycoplasma in view of Leen. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Xu and Leen are directed towards Coronavirus-specific polyclonal T cell compositions. The skilled artisan would have been motivated to do so because negativity for bacteria and fungi for at least 7 days in culture, less than 5 EU/ml of endotoxin, and negative for mycoplasma would be predictably advantageous ensure that Xu’s T cell composition is free from microbial contamination, and formulation for intravenous administration would be predictably advantageous to further administer the SARS-CoV2-specific T cells of Xu to subjects in need of treatment thereof for SARS-CoV2 infection in view of Leen.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 101 is alternatively rejected under 35 U.S.C. 103 as being unpatentable over Xu as evidenced by Qi, Sekine, Janeway, Rowntree, and Grifoni as applied to claim 1 above, and further in view of Vella et al. (J Exp Med (1997), 186(2), 325-330; Reference V).
The teachings of Xu as evidenced by Qi, Sekine, Janeway, Rowntree, and Grifoni are relied upon as set forth above.
Regarding claim 101, Xu as evidenced by Qi, Sekine, Janeway, Rowntree, and Grifoni do not teach any ex vivo/in vitro step of culturing SARS-CoV2-specific T cells with IL-4 and/or IL-7.
Vella teaches that culturing T cells in vitro with IL-4 and/or IL-7 improves the survival of the T cells (Abstract, and Fig. 1), reading on claim 101.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to further ex vivo/in vitro culture the SARS-Cov2-specific T cells of Xu with the IL-4 and/or IL-7 of Vella A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Xu and Vella are directed towards T cell compositions The skilled artisan would have been motivated to do so because Vella teaches that that culturing T cells in vitro with IL-4 and/or IL-7 is predictably advantageous to improves the survival of the T cells ex vivo/in vitro.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Double Patenting
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, 21, 24, 26-28, and 96 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27, 47, 51, 62, 64, and 66 of copending Application No. 17/597,879 (reference application) as evidenced by Sekine et al. (Cell (Oct 2020), 183, 158-168), Janeway et al. ( Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; (2001), NCBI Bookshelf reprint of Ch. 3, “Antigen recognition by T cells.”), and Rowntree et al. (PNAS (2024), 121(39), e2411428121; Reference U).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 66 (which depends, respectively, from claims 64, 62, 52, 47, and ultimately independent claim 27) of the copending ‘879 application is the narrower embodiment of a method which necessarily makes the ex vivo expanded and polyclonal T-lymphocyte composition specific for SARS-CoV2 of instant claims 1, 24, 26-28, and 96. The composition made by claim 66 of the copending ‘879 application only differs from the composition of instant claim 1 by reciting the non-structural antigens (e.g. the nsps) and structural antigens (e.g. Spike, Envelope, Matrix/Membrane, and Nucleocapsid proteins) as alternatives, but combining separate steps taught as useful in a method into a singular method must be held as prima facie obvious, as each step is taught separately useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). In this case, the non-structural antigens (e.g. the nsps) and structural antigens (e.g. Spike, Envelope, Matrix/Membrane, and Nucleocapsid proteins) are claimed as useful for the same purpose in making a T cell composition specific for SARS-CoV2, so combining the different embodiments of copending claim 66 into a single embodiment to yield the composition of instant claim 1 must be held prima facie obvious absent any showing of nonobviousness to the contrary.
Regarding claim 1, Sekine inherently shows that human CD4+ and CD8+ T cells specific against SARS-CoV2 are Th1 polarized and comprise memory cells (Abstract; p161, right column, paragraph starting “To access the functional capabilities..” and Fig. 3B, 3C, and 3D).
Regarding claim 1, Rowntree teaches that SARS-CoV2 infection in humans inherently yields a subset of effector T cells (p2, left column, paragraph starting “Introduction to COVID-19 vaccines…”).
Regarding claim 1, T cells inherently express αβ T cell receptors as evidenced by Janeway et al. ( Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; (2001), NCBI Bookshelf reprint of Ch. 3, “Antigen recognition by T cells.”). See the 1st paragraph under subheading 3-10 on the first page.
While Sekine and Rowntree are post-filed art, inherent features need not be recognized at the relevant time but only that the subject matter is inherent in the prior art reference, see M.P.E.P. § 2112 (II). Therefore, the polyclonal T cells made by claim 66 of the copending ‘879 application as evidenced Sekine, Rowntree, and Janeway inherently reads on the composition of instant claims 1, 21, 24, 26-28, and 96
Copending claim 66 of the ‘879 application recites one or more antigens selected from nsp1); nsp3; nsp4; nsp5; nsp6; nsp10; nsp12; nsp13; nsp14; nsp15, and/or nsp16, reading on instant claim 24.
Copending claim 66 of the ‘879 application recites one or more antigen selected from the group consisting of SARS-CoV-2 (AP3A); SARS-CoV-2 (NS7); SARS-CoV-2 (NS8); SARS-CoV-2 (ORF10); SARS-CoV-2 (ORF9B); and SARS-CoV-2 (Y14); one or more antigen selected from the group consisting of Spike (S); Envelope protein (E); Matrix/Membane protein (M); and Nucleocapsid protein (N); and one or more antigen selected from the group consisting of nsp1; nsp3; nsp4; nsp5; nsp6; nsp7a, nsp8, nsp10; nsp12; nsp13; nsp14; nsp15; and nsp16, reading on instant claims 26-28, and 96.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 20 and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27, 47, 51, 62, 64, and 66 of copending Application No. 17/597,879 (reference application) as evidenced by Sekine, Rowntree, and Janeway as applied to claim 1 above, and further in view of Leen et al. (WO 2011/028531; provided in the IDS dated 9/16/2022).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The teachings of the copending 17/597,879 reference application as evidenced by Sekine, Rowntree, and Janeway are relied upon as set forth above. Janeway further teaches that the main function of CD4 T cells that recognize MHC class II molecules is to activate other effector cells of the immune system (e.g. helper CD4 T cells; 6th page, the paragraph under Fig. 3.01) and CD8 T cells are cytotoxic and are specialized to kill any cell that they specifically recognize (the first paragraph of subheading 3-13 on the 5th page), reading in-part on claim 20.
Regarding claim 20, the copending ‘879 application does not claim CD4+ and CD8+ T-lymphocytes/cells. Regarding claim 41, the copending ‘879 application does not claim a polyclonal T cell composition further formulated for intravenous delivery, wherein the composition is negative for bacteria and fungi for at least 7 days in culture; exhibit less than 5 EU/ml of endotoxin, and is negative for mycoplasma.
Leen teaches methods and compositions for the generation and use of polyclonal cytotoxic T lymphocytes/cells (CTLs) that target multiple viruses and for administration to subjects in need of treatment thereof for infection (Abstract; the last paragraph on page 5 through the first paragraph on page 6; ¶0219), reading in-part on claims 20 and 41. Leen teaches the CTLs target at least one antigen from two or more viruses and including Coronavirus (¶0007), reading on claims 20 and 41. Leen teaches the CTLs are a mixture of CD4+ and CD8+ T cells for treating and/or preventing viral infection in subjects (¶0075; p7, the paragraph starting “To use T cells to target tumors..”; paragraph at the top of page 6), reading on claim 20. Leen teaches that criteria for administering the virus-specific CTLs includes negative culture for bacteria and fungi for at least 7 days in culture; exhibit less than 5 EU/ml of endotoxin, and negative for mycoplasma. (¶0159 on page 44), reading on claim 41. Leen teaches administering multivirus-specific T cells by intravenous injection (¶0160 on page 44), reading on claim 41.
Regarding claim 20, It would have been obvious to a person of ordinary skill in the art before the invention was filed to further select for CD4+ and CD8+ T cells in the methods of the copending ‘879 application in view of Leen and as evidenced by Janeway. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both copending ‘879 application and Leen are in-part directed towards Coronavirus-specific polyclonal T cell compositions. The skilled artisan would have been motivated to do so because Leen teaches targeting both CD4+ and CD8+ T cells to generate virus-specific T cells such as specific for Coronavirus and the evidentiary teachings of Janeway makes clear that the helper CD4+ and cytotoxic CD8+ T cells perform different biological functions during antigen recognition, and so the addition would predictably advantageous to generate a complete population of SARS-CoV2-specific T cells for the downstream treatment of Coronavirus infection in subjects in need thereof as taught by Leen.
Regarding claim 41, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further formulate the polyclonal T cells of claim 66 of the copending ‘879 application for intravenous administration, negative for bacteria and fungi for at least 7 days in culture; exhibit less than 5 EU/ml of endotoxin, and negative for mycoplasma in view of Leen. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both copending ‘879 application and Leen are in-part directed towards Coronavirus-specific polyclonal T cell compositions. The skilled artisan would have been motivated to do so because negativity for bacteria and fungi for at least 7 days in culture, less than 5 EU/ml of endotoxin, and negative for mycoplasma would be predictably advantageous ensure that the copending ‘879 application’s T cell composition is free from microbial contamination, and formulation for intravenous administration would be predictably advantageous to further administer the SARS-CoV2-specific T cells of the copending ‘879 application to subjects in need of treatment thereof for SARS-CoV2 infection in view of Leen.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 101 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27, 47, 51, 62, 64, and 66 of copending Application No. 17/597,879 (reference application) as evidenced by Sekine, Rowntree, and Janeway as applied to claim 1 above, and further in view of Vella et al. (J Exp Med (1997), 186(2), 325-330; Reference V).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The teachings of the copending 17/597,879 reference application as evidenced by Sekine, Rowntree, and Janeway are relied upon as set forth above.
Regarding claim 101, the copending ‘879 application does not claim any ex vivo/in vitro step of culturing SARS-CoV2-specific T cells with IL-4 and/or IL-7.
Vella teaches that culturing T cells in vitro with IL-4 and/or IL-7 improves the survival of the T cells (Abstract, and Fig. 1), reading on claim 101.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to further ex vivo/in vitro culture the SARS-Cov2-specific T cells of Leen with the IL-4 and/or IL-7 of Vella A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both copending ‘879 application and Vella are directed towards T cell compositions The skilled artisan would have been motivated to do so because Vella teaches that that culturing T cells in vitro with IL-4 and/or IL-7 is predictably advantageous to improves the survival of the T cells ex vivo/in vitro.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Response to Arguments
Applicant's arguments on pages 5-8 of the reply have been fully considered, but not found persuasive of error for the reasons given below.
On page 6 of the reply, Applicant alleges that the claimed T cells possess markedly different characteristics. This is not found persuasive of error because the argument amounts to a general allegation without rebutting the preponderance of evidence set forth by the examiner that the functional properties of independent claim 1 (i.e. Th1 polarization and memory and effector T cells) are present in the naturally-occurring SARS-CoV2 specific T cells of Xu as evidenced by Qi, Sekine and Rowntree and there is no evidence of record that the product-by-process limitations of the claims otherwise impart any markedly different characteristic compared to the naturally-occurring SARS-CoV2 specific T cells of Xu as evidenced by Qi, Sekine and Rowntree. “upon exposure” of claim 1 has been fully considered but is only a statement of intended use, and so Xu’s T cells are reasonably presumed capable of meeting the intended use of the claim(s).
On page 7 of the reply, Applicant alleges that Xu is deficient by not teaching ex vivo expanded T cells. This is not found persuasive because claim 1 and it’s dependent claims are product-by-process claims and which are not limited to the manipulations of the recited steps, only the structure implied by the steps. Applicant has not yet shown by any preponderance of evidence that the manufacturing process steps of the product-by-process claims (i.e. ex vivo expansion) impart any novel and/or non-obvious structural characteristics to the claimed T cell product as compared to the polyclonal T cell composition of Xu as evidenced by Qi which is inherently reactive to at least one structural antigen and at least one non-structural antigen as evidenced by Sekine, Rowntree, and Grifoni.
Applicant’s remarks regarding the nonstatutory double patenting rejections of record on pages 7-8 of the reply are acknowledged, but not found persuasive of error.
Conclusion
No claims are allowed. No claims are free of the art.
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.
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/Sean C. Barron/Primary Examiner, Art Unit 1653