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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in
37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 17, 2025 has been entered.
Claim Status
Claim listing filed on December 17, 2025 is pending. Claims 40-41 and 56-59 are amended. Claims 1-39, 50, and 52 are canceled. Claims 60-61 are new. Claims 42-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species. Claims 40-41, 44-49, 51, and 53-61 are examined upon their merits.
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. This application is a continuation-in-part of PCT/US2020/035618 filed on June 1, 2020 which claims the benefit of US Provisional Application No. 62/855,889 filed May 31, 2019. This application is also a continuation-in-part of PCT/US2021/049902 filed on September 10, 2021 which claims the benefit of US Provisional Application No. 63/076,923 filed September 10, 2020. Claims 40-46, 48-52, and 55-60 have support in PCT/US2020/035618 and receive an effective filing date of June 1, 2020. Claims 47 and 53-54 have support in PCT/US2021/049902 and receive an effective filing date of September 10, 2021. Claim 61 does not have support in any of the priority documents and receives an effective filing date of November 30, 2021.
Withdrawn Objections and Rejections
Applicant’s cancelation of Claims 50 and 52 have rendered all previous rejections and objections directed to these claims moot.
Amendments to the specification and claims overcome all objections of record, and the specification objections and claim objections are withdrawn.
Claim Objections (New, necessitated by amendment)
Claim 61 is objected to because of the following informalities: “CD4+ and/or CD8+ cell” should recite “CD4+ and/or CD8+ cells” wherein “cells” is plural as defined in the independent claim (Claim 59). Appropriate correction is required.
Claim Rejections - 35 USC § 112 (New, necessitated by amendment)
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.
Claim 60 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 60 recites “wherein said method is performed in a tissue culture system.” “Said method” in Claim 60 refers to “a method for treating a disease, disorder, or condition caused by infection by SARS-CoV-2 comprising administering to a subject in need thereof T cells” as defined in independent Claim 59. The method of Claim 59 is performed in “a subject” which the specification defines as an animal (page 31). Therefore, Claim 60 is indefinite because it is unclear how the method can be performed in an animal and in a tissue culture system when the two models are distinct. Animals are in vivo having complete organ systems while tissue culture systems are in vitro having isolated cells in artificial media. For the purpose of compact prosecution, Claim 60 is interpreted as “wherein said contacting is performed in a tissue culture system” which refers to contacting a sample of autologous T cells with at least one SARS-CoV-2 peptide epitope as defined in Claim 59. For clarity of record, Claim 60 is further interpreted as “a tissue culture system comprising (1) a plurality of lymphocytes positioned within at least one vessel, (2) cell culture media, and (3) a composition comprising said cytokines.” The term “vessel” is not defined in the specification and the broadest reasonable interpretation of “vessel” encompasses any flask, dish, plate, tube, or consumable known to be suitable for cell culture prior to the effective filing date.
Claim Rejections - 35 USC § 112 (New)
Claims 55-57 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.
Claims 55-57 recite “a subject in need thereof or to a subject deficient in therapeutically effective number of said T cells.” Claims 55-57 depend from Claim 40 which also recites “a subject in need thereof.” Therefore, three separate subjects are defined. Claims 55-57 further recite “wherein said subject has been infected with SARS-CoV-2.” It is unclear which of the three possible subjects is referred to as “said subject.” For the purpose of compact prosecution, Claims 55-57 are interpreted as “wherein said administering comprises administering CD8+ and/or CD4+ memory effector T cells which recognize a SARS-CoV-2 peptide epitope or other viral epitope to the subject in need thereof or to the subject deficient in therapeutically effective numbers of said CD4+ and CD8+ memory effector T cells; wherein said subject has been infected with SARS-CoV-2.” This interpretation narrows the claim language to one subject wherein the subject has a disease, disorder, or condition caused by SARS-CoV-2 and optionally wherein the subject is deficient in in therapeutically effective numbers of said CD4+ and CD8+ memory effector T cells.
Note, Claim 41 is interpreted as “wherein said contacting comprises contacting the T cells with IL-6 and IL-15 under conditions favoring outgrowth of CD8+ T cells compared to outgrowth of CD4+ T cells, and (1) isolating CD8+ central memory T cells expressing CD45RO, CCR7 and L-selectin from other cells in the culture; or (2) isolating CD8+ effector memory T cells expressing CD45RO without expressing CCR7 or L-selectin from other cells in the culture.” Therefore, Claim 41 encompasses contacting the T cells with IL-6 and IL-15 under conditions favoring outgrowth of CD8+ T cells compared to outgrowth of CD4+ T cells and either (1) or (2).
Claim Rejections - 35 USC § 112 (New, necessitated by amendment)
Claim 61 is 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.
Claim 61 recites “wherein said culture comprising CD4+ and/or CD8+ cells is administered to a neonate.” A “neonate” is understood in the art as a newborn infant within their first 28 days of life (or four weeks). Remarks filed 12/17/2025 state that Claim 61 finds support on pages 3 and 5 of the specification; however, nowhere in the specification teaches the therapeutic administration of T cells to neonates. Specification page 6 states that antigen-specific T cells can be used to treat infections by neonatal pathogens including rubella, CMV, hepatitis A, hepatitis B, HIV, and herpes simplex virus. Therefore, the specification provides written description for treating these viruses, but patients of all ages can contract these viral infections. Listing these viruses and describing them as “neonatal pathogens” is distinct from administering antigen-specific T cells to newborn infants. The disclosure provides no support for administering T cells to neonates, and Claim 61 is rejected for being directed to new matter.
Claim Rejections - 35 USC § 112 (Modified)
Claims 40-41, 44-49, 51, and 53-61 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating SARS-CoV-2 by administering virus-specific T cells, does not reasonably provide enablement for treating any disease, disorder, or condition caused by a viral infection by administering T cells specific for any viral peptide. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
It is of record in the non-final rejection filed on May 1, 2025 that the state of the art prior to filing provides enablement for a method of treating SARS-CoV-2 by administering SARS-CoV-2-specific T cells. Claims 40-41, 47-49, 51, and 53-54 are directed to a method of treating any disease, disorder, or condition caused by any viral infection by administering T cells primed with any viral peptide epitope. Claims 44-46 are directed to a method of treating any disease, disorder, or condition caused by any viral infection by administering T cells primed with a SARS-CoV-2 viral peptide epitope. Claims 55 and 57 are directed to treating any disease, disorder, or condition caused by SARS-CoV-2 by administering T cells primed with any viral peptide epitope. Claims 56 and 58-61 are directed to treating any disease, disorder, or condition caused by SARS-CoV-2 by administering T cells primed with a SARS-CoV-2 viral peptide epitope. Therefore, the claims are not enabled because they are not directed to a method of treating SARS-CoV-2 by administering SARS-CoV-2-specific T cells as of record in the non-final rejection filed on May 1, 2025.
It is important to note that the specification is enabled for “a method of treating SARS-CoV-2 by administering SARS-CoV-2-specific T cells” but not enabled for “a method of treating a disease, disorder, or condition caused by infection by SARS-CoV-2 by administering SARS-CoV-2-specific T cells.” Cleveland Clinic 2025 teaches that SARS-CoV-2 can cause serious complications including pneumonia, blood clots, and cardiac arrest (“Complications of COVID”). Therefore, “a disease, disorder, or condition caused by infection by SARS-CoV-2” broadly encompasses conditions such as pneumonia, blood clots, and cardiac arrest. There is no evidence in the state of the art prior to filing or in the instant specification that SARS-CoV-2-specific T cells can be administered to treat conditions such as pneumonia, blood clots, or cardiac arrest. There is only evidence that SARS-CoV-2-specific T cells can effectively treat SARS-CoV-2 viral infection.
Further, there is considerable unpredictability in treating newborn infants less than 4 weeks of age with immunotherapy (Claim 61), and the instant specification does not overcome this unpredictability because it teaches no examples of treating any type of disease by administering any type of antigen-primed T cell in any type of subject.
Applicant's arguments filed December 17, 2025 have been fully considered but they are not persuasive. Applicant argues that the rejection cannot be sustained in light of the amendment of the claims to disease, disorders, or conditions caused by SARS-CoV-2 which have been indicated as enabled. Examiner discusses the difference between (1) treating SARS-CoV-2 (enabled) and (2) treating diseases, disorders, or conditions caused by SARS-CoV-2 (not enabled) in the rejection above. Further, the majority of the claims are still directed to treating disease, disorders, or conditions caused by any viral infection by administering T cells primed with any viral peptide epitope. Applicant’s arguments are not persuasive, and the rejection is maintained.
Claim Rejections - 35 USC § 102 (Modified, necessitated by amendment)
Claims 40-41, 47-49, 51, and 53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Houghtelin et al. Front Immunol. (of record) as evidenced by Reiser et al. J Immunol Res. 2016.
MPEP §2131.01 provides guidance as to 35 U.S.C. 102 rejections over multiple references. Such rejection has been held to be proper when the extra references are cited to: (C) Show that a characteristic not disclosed in the reference is inherent.
The MPEP states: “To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence. Such evidence must make clear that the missing descriptive matter is necessarily present in the thing described in the reference, and that it would be so recognized by persons of ordinary skill.” Continental Can Co. USA v. Monsanto Co., 948 F.2d 1264, 1268, 20 USPQ2d 1746, 1749 (Fed. Cir. 1991) (The court went on to explain that “this modest flexibility in the rule that 'anticipation' requires that every element of the claims appear in a single reference accommodates situations in which the common knowledge of technologists is not recorded in the reference; that is, where technological facts are known to those in the field of the invention, albeit not known to judges.” 948 F.2d at 1268, 20 USPQ at 1749-50.). Note that the critical date of extrinsic evidence showing a universal fact need not antedate the filing date. See MPEP §2124.
The teachings of Houghtelin as they apply to Claims 40-41, 47-49, 51, and 53 are of record in the final office action filed 09/11/2025. It is of record that the virus-specific T cells (VSTs) are CD4+ and CD8+ effector memory T cells (page 3, paragraphs 3-4; page 2, paragraph 4; page 7, paragraph 4). Houghtelin does not specifically recite wherein the CD8+ effector memory T cells express CD45RO without expressing CCR7 or L-selectin (Claim 41), but these markers are inherent to CD8+ effector memory T cells as evidenced by Reiser. Reiser is relied upon solely as evidence that CD8+ effector memory cells are classified by CD45RO+ CCR7- CD62L- surface markers (Table 1). Note, CD62L is synonymous with L-selectin. Thus, the claimed markers are inherent to the CD8+ effector memory T cells taught by Houghtelin.
Claims 40-41, 47-49, 51, and 53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Houghtelin as evidenced by Reiser.
Applicant's arguments filed December 17, 2025 have been fully considered but they are not persuasive.
Applicant argues that Houghtelin teaches the treatment of CMV, EBV, adenovirus, BK virus, and herpes virus but does not teach treating SARS-CoV-2. Applicant further argues that Houghtelin does not teach treatment of a subject with T cells primed with a SARS-CoV-2 epitope within SEQ ID NO: 11. However, Claim 40 recites “a method of treating a disease, disorder, or condition caused by a viral infection” and the broadest reasonable interpretation of “viral infection” encompasses any virus which is anticipated by Houghtelin (MPEP § 2111). Claim 40 does not require the viral infection to be SARS-CoV-2. Further, Claim 40 recites “administering to a subject in need thereof T cells produced by: contacting a sample of T cells comprising CD4+ and/or CD8+ T cells with at least one viral peptide epitope.” Therefore, the T cells can be primed with any viral peptide epitope, and the claim does not limit the epitope to be within SEQ ID NO: 11. For clarity, Applicant elected species (B) “T cell that recognizes a viral SARS-CoV-2 epitope from Spike protein” from the species requirement reciting “a species of T cell that recognizes a SARS-CoV-2 epitope from either the Spike, Membrane, Envelope, or Nucleocapsid protein” (of record in the restriction requirement filed 01/24/2025) which reads on instant Claim 44 only. Similarly, Applicant elected species (C) “an epitope contained within SEQ ID NO: 11” from the species requirement reciting “a structurally distinct peptide epitope selected from SEQ ID NOs: 50-515” (of record in the restriction requirement filed 01/24/2025) which reads on Claims 45 and 58 only.
Applicant reiterates Examiner’s interpretation that the T cells of Claim 40 are defined as a product-by-process and are evaluated for patentability by the structure implied by the process steps which is a sample of T cells comprising CD4+ and/or CD8+ T cells that are primed with a viral peptide. Applicant argues that Examiner fails to evaluate all of the structures implied by the recited process, specifically (i) T cells that are primed to a peptide contained within SEQ ID NO: 11 and (ii) T cells exposed to the combination of IL-6 and IL-15. Applicant argues that T cells exposed to IL-6 and IL-15 have distinct surface phenotypes such as “upregulated specific transcription factors and chemokine receptors” and “upregulation of receptors associated with memory and homeostatic proliferation.” In regard to structural argument (i), Houghtelin teaches wherein the VSTs recognize at least one viral epitope (of record) which reads on the T cells of Claim 40. The viral epitope is not required to be within SEQ ID NO: 11 for the reasons outlined above. In regard to structural argument (ii), Examiner interprets that contacting the T cells with the recited combinations of cytokines causes no structural changes to the T cells. This interpretation is based on the understanding in the art prior to filing that T cell culture protocols typically require the addition of cytokines to support expansion (Tanabe, Biocompare 2019; “Media components” and “What You Need to Know about T Cell Culture”). Therefore, Examiner interprets that contacting the T cells with the recited cytokines supports T cell proliferation but does not impose structural changes on the T cells. The instant specification does not teach specific structural implications caused by contacting the T cells with the cytokines. Further, Applicant vaguely states that transcription factors, chemokine receptors, and other receptors can be upregulated as a result of contact with the cytokines, but these generalizations fail to specifically point out how the instantly claimed T cells structurally differ from the prior art T cells. MPEP § 2113.II states “Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing a nonobvious difference between the claimed product and the prior art product.“ As no concrete evidence of a nonobvious structural difference between the T cells was presented, the rejection is maintained.
Claim Rejections - 35 USC § 102 (Maintained)
The rejection of Claims 40 and 54 under 35 U.S.C. 102(a)(1) as being anticipated by Leen et al. Blood (of record) is maintained.
Applicant's arguments filed December 17, 2025 have been fully considered but they are not persuasive. Applicant argues that Leen does not teach the treatment of SARS-CoV-2 or modifying T cells by exposure to IL-6 and IL-15. However, the claims are directed to any viral infection (as explained in detail in the 102 rejection above) which is anticipated by Leen, and the exposure to IL-6 and IL-15 does not result in a nonobvious structural difference between the instant T cells and the T cells taught by Leen (as explained in detail in the 102 rejection above). The arguments are not persuasive, and the rejections are maintained.
Claim Rejections - 35 USC § 103 (Maintained)
The rejection of Claims 46 and 55-57 under 35 U.S.C. 103 as being unpatentable over Houghtelin et al. Front Immunol. 2017 (of record) as applied to Claims 40-41, 47-49, 51, and 53 above, and further in view of NCT04351659 ClinicalTrials.gov (of record) is maintained.
Applicant's arguments filed December 17, 2025 have been fully considered but they are not persuasive. Applicant argues that the cited references do not teach the specific process steps required by claim 40 which require exposure of T cells to IL-6 and IL-15. As stated repeatedly on the record and addressed in the rejections above, Claim 40 describes the T cells as a product-by-process. Because the T cells are a product-by-process, it does not matter how the T cells were produced (in vivo or in vitro); the patentability is determined based on the product itself. The arguments are not persuasive, and the rejection is maintained.
Claim Rejections - 35 USC § 103 (Modified, necessitated by amendment)
Claims 44-45 and 58-60 are rejected under 35 U.S.C. 103 as being unpatentable over Houghtelin et al. Front Immunol. 2017 (of record) in view of NCT04351659 ClinicalTrials.gov (of record) as applied to Claims 40-41, 46-49, 51, 53, and 55-57 above, and further in view of Yang et al. Clin Immunol. 2006 (of record) and GenBank: QHD43416.1 (of record).
The teachings of Houghtelin in view of NCT04351659 as they apply to Claims 40-41, 46-49, 51, 53, and 55-57 are of record and comprise a method of treating SARS-CoV-2 by administering SARS-CoV-2-specific CD4+ and/or CD8+ T cells. It is of record that Houghtelin teaches wherein the T cells are autologous or allogenic. Houghtelin specifically teaches that VSTs derived from unmatched donors and not autologous or HLA-matched sources carry an increased risk of graft-versus-host disease (GVHD) (page 5, paragraph 1). Houghtelin in view of NCT04351659 fails to teach wherein the T cells recognize the SARS-CoV-2 Spike (S) protein (Claim 44) or wherein the T cells recognize an epitope present on SEQ ID NO: 11 (Claims 45 and 58-60).
Yang teaches that SARS-CoV Spike (S) protein-specific memory CD4+ and CD8+ T cells in peripheral blood of recovered SARS patients were persistent for more than 1 year after infection (page 172, paragraph 3). GenBank: QHD43416.1 teaches that the sequence of the Spike protein for the SARS-CoV-2 strain was known prior to the effective filing date of the instant application and is 100% identical to instant SEQ ID NO: 11 (Genbank sequence).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, that the T cells taught by NCT04351659 would recognize an epitope on the SARS-CoV-2 Spike protein comprising SEQ ID NO: 11. NCT04351659 teaches that SARS-CoV-2-specific T cells from convalescent donors who have recovered from COVID-19 can be isolated and administered to treat patients with severe SARS-CoV-2 infections. Yang teaches that CD4+ and CD8+ T cells recovered from SARS patients recognize the Spike protein for more than 1 year after infection, and the specific sequence of the SARS-CoV-2 Spike protein was known to be SEQ ID NO: 11 prior to filing. Because of the long-term SARS-CoV Spike-specific memory of T cells, it is obvious that the T cells isolated from patients post-infection were primed with an epitope from the SARS-CoV-2 Spike protein. The motivation to administer T cells primed with an epitope from the SARS-CoV-2 Spike protein is because the SARS-CoV Spike-specific memory of T cells is known to provide long-term immunity, persisting for more than 1 year after infection (Yang page 172, paragraph 3). While NCT04351659 teaches administering allogenic SARS-CoV-2-specific T cells, the teachings of Houghtelin provide the motivation to administer autologous SARS-CoV-2-specific T cells back to patients in need thereof because autologous VSTs are understood to have a lower rejection risk such as a reduced risk of graft-versus-host disease (GVHD) (page 5, paragraph 1).
Applicant's arguments filed December 17, 2025 have been fully considered but they are not persuasive. Applicant argues that Yang provides no motivation to modify T cells by exposure to IL-6 and IL-15. As discussed above, the cited references are not required to teach the process steps (i.e. contact with IL-6 and IL-15) in a product-by-process claim (MPEP § 2113).
Double Patenting (Maintained)
The nonstatutory double patenting rejections numbered #1-11 of record in the final office action filed 09/11/2025 are maintained.
Applicant's arguments filed December 17, 2025 have been fully considered but they are not persuasive. Applicant argues that the rejections cannot be sustained in light of the limitation of the claims to a method of treating SARS-CoV-2 and in view of the lack of any suggestion to use T cells modified by exposure to IL-6 or IL-15. As discussed above, Examiner maintains that Claim 40 is directed to treating a disease, disorder, or condition caused by any type of viral infection, and the T cells of Claim 40 are a product-by-process wherein the process of contacting the T cells with IL-6 and IL-15 results in no structural difference in the T cells. The rejections are maintained.
Conclusion
No claim is allowed.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/STACEY N MACFARLANE/Examiner, Art Unit 1675
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