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 .
DETAILED ACTION
Applicant’s election with traverse of a specific cancer: synovial sarcoma in the reply filed on December 3, 2025 is acknowledged.
Applicant’s traversal is on the grounds that the examiner has not provided evidence that the claimed species have achieved a separate status in the art or would require a different field of search and that therefore the examiner has not established a serious search burden for searching all species together. In view of prior art (see 103 rejections below), the applicant’s traversal is found persuasive. Accordingly, the restriction requirement as set forth in the Office action mailed on September 8, 2025 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 79 and 91 have been amended.
Claims 76-91 are pending and under consideration.
Priority
It is acknowledged that this application claims the benefit of priority to U.S. Provisional Patent Appl. No. 63/277,074 filed November 8, 2021. The priority date has been established as November 8, 2021.
Information Disclosure Statement
The Information Disclosure Statements filed on 11/08/2022, 02/28/2023, 02/28/2023, 02/28/2023, 02/28/2023, 11/10/2023 and 12/03/2025 have been considered and entered by examiner.
Specification
The disclosure is objected to because of the following informalities: The current application was filed after July 1, 2022, thus the WIPO Standard ST.26, Sequence Listing in XML format, applies to sequence disclosures. See 37 CFR § 1.831. An ST.26 Sequence Listing in XML must not include any sequences having fewer than 10 specifically defined nucleotides, or fewer than 4 specifically defined amino acids. See 37 CFR § 1.831(j).
The specification filed 02/06/2023 refers SEQ ID NOs: 13, 25, 37, 49, 73, 85, 97 and 109 (e.g. paragraphs [0032], [00258], and Table 7). These sequences are replaced with “000” in the Sequence Listing in XML because the sequences are less than 4 amino acid sequences. The SEQ ID NOs: 13, 25, 37, 49, 73, 85, 97 and 109 in the specification should be deleted and replaced with corresponding amino acid sequences because the Sequence Listing in XML does not contain the short sequences.
Appropriate correction is required.
Claim Objections
Claim 77 objected to because of the following informalities: “SEQ ID NO: 109” should be replaced by “MTL”. As set forth above, SEQ ID NO: 109 is replaced with “000” in the Sequence Listing in XML because the sequence is less than four amino acids in length.
Appropriate correction is required.
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.
Claims 79, 81, 85-88 and 91 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.
Regarding claim 79, the phrase "preferably" at line 2 and line 3 renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 79, the phrase "(approximately 550,000 IU/m2)" at line 5 renders the claim indefinite because it is unclear whether the limitation(s) in the parenthesis is part of the claimed invention.
Claim 81 recites the limitation "the IL-2" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 81, the phrase "(approximately 550,000 IU/m2)" at line 5 renders the claim indefinite because it is unclear whether the limitation(s) in the parenthesis is part of the claimed invention.
Regarding claim 85, the phrase "preferably" at page 5-line 2 renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention.
Regarding claim 86, the phrase "preferably" at line 2 renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention.
Regarding claim 88, the phrase "preferably" at lines 12, 14, and 16 renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention.
Regarding claim 91, the phrase "preferably" at lines 3, 5, 14, 15, 16, 17, 19 and 21 renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention.
Regarding claim 91, the phrase "may be carried out" at page7-line 1 renders the claim indefinite because it is unclear whether the step associated with the phrase is part of the claimed invention.
Claim 91 recites “(i) thawing PBMCs on day 0”, “(ii) thawing PBMCs on day 1”, “(iii) thawing PBMCs on day 1”, and “(iv)…on day 8-10” . It is unclear what the reference time is used for day 0 or day 1 or day 8-10.
Claim 87 is also rejected because it depends on claim 86.
Claim Rejections - 35 USC § 112
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 80 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 80, which depends on claim 76, recites “(ii) approximately 0.08 x 109 cells …”. “Approximately 0.08 x 109 cells” is the same as “approximately 0.8 x 108 cells”. However, claim 76 recites a dose of approximately 1 x 108 to approximately 10 x 1010 cells. Thus, claim 80 broadens the scope of claim 76.
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 § 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 76-91 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. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to methods of treating a cancer comprising administering a therapeutically effective amount of engineered T cells to a subject in need thereof, wherein said engineered T cells: (i) are αβ T-cells and/or γδ T-cells; and (ii) express a TCR, wherein said TCR comprises a TCR α chain and a TCR β chain, wherein said TCR α chain comprises the CDR1, CDR2, and CDR3 sequences as comprised in SEQ ID NO: 111, and wherein said TCR β chain comprises the CDR1, CDR2, and CDR3 sequences as comprised in SEQ ID NO: 117; and wherein said T cells are administered at a dose of approximately 1 x 108 to approximately 10 x 1010 cells. The specification describe R11P3D3 and R11P3D3_KE which comprise the recited CDR combinations and bind specifically to a PRAME-004 peptide (SLLQHLIGL) (see Examples 18 and 39, and [0780] of the instant publication US 2023/0192886 A1). As evidenced by claim 78, the TCR however is not limited to the R11P3D3 or R11P3D3_KE. By reciting “a TCR α chain having at least 70%, 80%, 90%, 95%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 113, and a TCR β chain having at least 70%, 80%, 90%, 95%, 98%, 99%, or 100% sequence identity to the amino acid sequence of SEQ ID NO: 119”, the claims encompass an enormous number of variants of SEQ ID NO: 113 and SEQ ID NO: 119. In addition, the claims encompass a broad genus of cancers which may or may not express the PRAME-004 peptide targeting by the recited TCR. The specification provides insufficient written description to support the genus encompassed by the claims.
Vas-Gath, Inc. v" Mahurkar, 19 USPQ2d 1111, makes clear that "to satisfy the written description requirement, an 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, and that the invention, in that context, is whatever is now claimed".
Regarding up to 30% variation to SEQ ID NO: 113 or SEQ ID NO: 119, although the claims limit the CDRs 1-3 and CDRs 1-3 for the TCR α chain and β chain, it is well known in the art that mutations in the variable domain of a TCR, even outside the CDRs, can significantly impact target binding. Mutations in the framework regions (non-CDR areas) can alter the structure and dynamics of the TCR, affecting its ability to bind to its target antigen. For example, even single amino acid change in the framework position can lead to deleterious impact on the TCR, see § Fig. 2 and the bridging paragraph of cols. 1-2 on page 3 of Rosenberg (Rosenberg et al., Front. Immunol., 15: 1345368, Publication Date: 03/12/2024).
In view of above, other than general description, the specification teaches only two TCRs: R11P3D3 and R11P3D3_KE which can specifically binds to the PRAME-004 peptide (SLLQHLIGL) and comprise the recited CDRs. Given the length of SEQ ID NO: 113 (273 amino acids in length) and SEQ ID NO: 119 (311 amino acids in length), the claims encompass variants with more than 80 amino acid variations including insertions, deletions and/or substitutions. In addition, the specification does not identify structure, physical and/or chemical properties, or functional characteristics coupled with correlation between structure and function for the broad genus of TCR and variants thereof. A skilled artisan cannot visualize or recognize the identity of the members of the TCR variants that exhibit the functional properties of the claimed invention as whole.
Regarding the broadly claimed cancers, Gerdes et al. (Front. Oncol. 12/18/2014 doi: 10.3389/fonc.2014.00366, pp. 1-12) teach that cancer is a multifaceted disease characterized by heterogeneous genetic alterations, cellular metabolism at the organ, tissue, and cellular levels and these conditions vary between cancers. See abstract and Fig. 1. Gerdes et al. teach that the tumor microenvironment is a highly heterogeneous mix of cellular and non-cellular components and can promote or be antagonistic to tumor growth. See Tumor Microenvironment-Heterogeneity and Anticancer Therapeutic Target-pp. 5-6 and Fig. 1. Consistent with this, PRAME expression levels in different cancers vary significantly. Yi (Yi et al., BJUI Compass, 2025:6:e70037, Publication Year: 2025) teaches that PRAME is not a frequently expressed antigen in renal cell carcinoma (Title and Figs. 1 B, 1C and 1D). The PRAME expression levels vary even in the patients with same cancers (see data for NSCLC samples in Fig. 1C and Fig. 1D).
In view of above, the instant specification discloses a working example in which TCR T cells comprising R11P3D3_KE show anti-tumor activity for a PRAME-0004+ and HLA-A*2 + cancer. Accordingly, one of ordinary skilled in the art would not be able to readily recognize/visualize cancers which would be suitable for the claimed treatment.
Taken together, the instant specification has not provided a sufficient description for the TCRs for treating all possible cancers encompassed by the claims. The ordinary artisan could reasonably conclude based on a survey of the data shown in the instant specification that Applicants were not in possession of the claimed invention.
Claims 76-91 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:
a method of treating a PRAME positive cancer comprising administering a therapeutically effective amount of engineered T cells to a subject in need thereof, wherein the PRAME positive cancer expresses a PRAME peptide with the sequence of SEQ ID NO: 310 (SLLQHLIGL) and is HLA-A*2 positive, wherein said engineered T cells: (i) are αβ T-cells and/or γδ T-cells; and (ii) express a TCR, wherein said TCR comprises a TCR α chain comprises the amino acid sequence of SEQ ID NO: 113 and wherein said TCR β chain comprises the amino acid sequence of SEQ ID NO: 119; and wherein said T cells are administered at a dose of approximately 1 x 108 to approximately 10 x 1010 cells,
does not reasonably provide enablement for:
“a method of treating a cancer comprising administering a therapeutically effective amount of engineered T cells to a subject in need thereof, wherein said engineered T cells: (i) are αβ T-cells and/or γδ T-cells; and (ii) express a TCR, wherein said TCR comprises a TCR α chain and a TCR β chain, wherein said TCR α chain comprises the CDR1, CDR2, and CDR3 sequences as comprised in SEQ ID NO: 111, and wherein said TCR β chain comprises the CDR1, CDR2, and CDR3 sequences as comprised in SEQ ID NO: 117; and wherein said T cells are administered at a dose of approximately 1 x 108 to approximately 10 x 1010 cells”.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. This is a SCOPE OF ENABLEMENT rejection.
As set forth above, the claims are drawn to an antigen recognize TCR comprising the CDR1, CDR2 and CDR3 of SEQ ID NO: 111; and CDR1, CDR2 and CDR3 of SEQ ID NO: 113. Dependent claim 78 further limits the sequence of TCR α chain to SEQ ID NO: 113 or a sequence with 70% identity to SEQ ID NO: 113, and the sequence of TCR β chain to SEQ ID NO: 119 or a sequence with 70% identity to SEQ ID NO: 119. It is also noted that the broadest claims do not identify the target of the antigen recognizing TCR. The specification discloses that TCR R11P3D3_KE comprises SEQ ID NO: 113 and SEQ ID NO: 119 (Table 7 on pages 55-56).
The specification discloses that R11P3D3_KE shows superior sensitivity to targeting peptide: PRAME-0004 (Example 8, [0654]). It is noted that PRAME-004 has the sequence of SLLQHLIGL (SEQ ID NO: 310), see Table 7 on page 69. As set forth above, the claims are not limited to TCR R11P3D3 or R11P3D3_KE, but include an enormous numbers of variants which can have more than 80 amino acid variations outside of the CDR regions. It is well known in the art that even single amino acid change in the framework position can lead to deleterious impact on the TCR, see § Fig. 2 and the bridging paragraph of cols. 1-2 on page 3 of Rosenberg (Rosenberg et al., Front. Immunol., 15: 1345368, Publication Date: 03/12/2024). The specification does not disclose the structure of any other TCR variants comprising an alpha chain and beta chain as claimed are capable of binding to PRAME-004/HLA-A*2. Further, the specification does not identify structure, physical and/or chemical properties, or functional characteristics coupled with correlation between structure and function for the broad genus of TCR and TCR variants. A skilled artisan cannot visualize or recognize the identity of the members of the TCR variants that exhibit the functional properties of the claimed invention as whole.
In addition, the claims encompass a broad genus of cancers. Gerdes et al. (Front. Oncol. 12/18/2014 doi: 10.3389/fonc.2014.00366, pp. 1-12) teach that cancer is a multifaceted disease characterized by heterogeneous genetic alterations, cellular metabolism at the organ, tissue, and cellular levels and these conditions vary between cancers. See abstract and Fig. 1. Gerdes et al. teach that the tumor microenvironment is a highly heterogeneous mix of cellular and non-cellular components and can promote or be antagonistic to tumor growth. See Tumor Microenvironment-Heterogeneity and Anticancer Therapeutic Target-pp. 5-6 and Fig. 1. Consistent with this, PRAME expression levels in different cancers vary significantly. Yi (Yi et al., BJUI Compass, 2025:6:e70037, Publication Year: 2025) teaches that PRAME is not a frequently expressed antigen in renal cell carcinoma (Title and Figs. 1 B, 1C and 1D). The PRAME expression levels vary even in the patients with same cancers (see data for NSCLC samples in Fig. 1C and Fig. 1D). Accordingly, the therapeutic activity of the claimed TCRs, which targets to a PRAME peptide, on a cancer is unpredictable.
In view of above, the instant specification discloses a working example in which TCR T cell comprising R11P3D3_KE shows anti-tumor activity for a PRAME-0004+ and HLA-A*2 + cancer. As a result of the unpredictability in the prior art as discussed above, this limited disclosure is not sufficient to provide adequate guidance for all TCRs and all cancers encompassed by the claims.
The specification and prior art provide insufficient guidance with regard to these
issues and provides insufficient working examples which would provide guidance to one
skilled in the art and no evidence has been provided which would allow one of skill in
the art to predict that the invention will function as contemplated or claimed with a
reasonable expectation of success. For the above reasons, it appears that undue
experimentation would be required to practice the claimed invention in its full scope.
Due to the large quantity of experimentation necessary to test the use of all
TCRs and variants for treating all possible cancers encompassed by the claims; the lack of direction/guidance presented in the specification and prior arts; the state of the prior art which establishes the unpredictability in TCR and cancer therapy in general; and the breadth of the claims, undue experimentation would be required for the skilled artisan to use the claimed invention in its full scope.
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.
Claims 76-91 are rejected under 35 U.S.C. 103 as being unpatentable over Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
Mata teaches engineered T cells can induce immune response ([0039]).
Mata teaches several TCRs including R11P3D3 and R11P3D3KE which binds peptide PRAME-004 (SLLQHLIGL) SEQ ID NO: 147 in a complex with an MHC molecule ([00139], and Table 1). It is noted that R11P3D3KE appears to be the same TCR used in the instant Example 39. As evidenced by instant specification, R11P3D3KE comprises a TCR alpha variable domain of SEQ ID NO: 111 and a TCR beta variable domain of SEQ ID NO: 117; a full length TCR alpha chain of SEQ ID NO: 113 and a full length TCR beta chain of SEQ ID NO: 119 (Table 7 on page 55 of the instant publication US 2023/0192886 A1). Thus, R11P3D3KE of Mata reads on the TCR of instant claims 76-78.
Mata teaches a method of preparing T cells for immunotherapy, including activating the T cells, transducing the activated T cells with the vector comprising the TCR, and expanding the transduced T cells ([0042], claims 1-5, and 27).
Mata teaches the T cells may be αβ T cells, and/or γδ T cells ([0043]).
Mata teaches the method of preparing engineered γδ T cells expressing an engineered TCR (Example 2). Mata also teaches the method of engineered αβ T cells expressing an engineered TCR (Example 7).
Mata teaches that the αβ T cells expressing engineered TCR construct are functionally active and specific for antigen-positive target cells, such as inducing IFN-γ expression, Granzyme B expression ([0225-0229], Figs. 26-29, and Example 8)
Mata teaches a method of treating a patient who has cancer comprising administering to the patient a composition the population of expanded T cells, wherein the T cells kill cancer cells that present a peptide in a complex with an MHC molecule on the surface including SEQ ID NO: 147 (SLLQHLIGL), wherein the cancer is selected from wherein the cancer is selected from the group consisting of non-small cell lung cancer, small cell lung cancer, melanoma, liver cancer, breast cancer, uterine cancer, Merkel cell carcinoma, pancreatic cancer, gallbladder cancer, bile duct cancer, colorectal cancer, urinary bladder cancer, kidney cancer, leukemia, ovarian cancer, esophageal cancer, brain cancer, gastric cancer, and prostate cancer (claim 35).
Mata teaches that the administration regimens for engineered T cells can be adjusted based on the severity and course of the disease or condition, previous therapy, the subject’s health status, weight, and/or response to drugs, and/or the judgement of the treating physician ([0149]).
Taken together, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE. However, Mata does not teach the T cells are administered at a dose of approximately 1 x 108 to approximately 10 x 1010 cells.
Heemskerk teaches methods for treating hyperproliferative diseases by inducing an immune response against Preferentially Expressed Antigen of Melanoma (PRAME) antigen; the immune response may be induced by specifically targeting PRAME-expressing cells using T cell receptors directed against PRAME (Abstract and [0003]).
Heemskerk teaches isolation of high affinity PRAME specific T cells that recognize the PRAME-derived peptide SLLQHLIGL (SEQ ID NO: 89) (SLL). Heemskerk teaches that the high affinity PRAME specific T cell clones showed high reactivity against a panel of PRAME positive tumor cell lines and against metastatic melanoma, sarcomas, and primary AML cells, and no reactivity against normal cell type ([0507], [1030]). It is noted that the PRAME-derived peptide SLLQHLIGL (SEQ ID NO: 89) is identical to the PRAME-0004 peptide bound by R11P3D3KE.
Heemskerk teaches that human T cells transduced with the pSFG-iC9.2A.PRAME derived Cell A vector. Cell A T cells, comprising the TCR that recognize SLLQHLIGL, are effective against tumors in vivo ([0507]-[0511] and Figs. 4 and 6).
Heemskerk teaches that the effective amount of the engineered T cells may be determined by a physician, considering the individual patient. Factors to be considered may include the extent of the disease or condition, tumor size, extent of infection, metastasis, age, and weight [0391]. For example, the Cell A Dose level can be about 5 x 106 cells/kg (Table 1 on page 34). Thus, for a 60 kg adult, the dose would be 3 x 108 cells which would read on the dose range of the instant claims 76 and 80.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL with engineered αβ T cells, and/or γδ T cells expressing the TCR such as R11P3D3KE which recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including melanoma, lung cancer…) with said T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including melanoma and lung cancer (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Mata (such as R11P3D3KE ) for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) because these cancers would be targeted by the T cells expressing R11P3D3KE. Based on the antigen-dependent activity of engineered TCR T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising R11P3D3KE would be able to induce immune response against cancers expressing SLLQHLGL in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claim 79, Mata teaches the method further comprises an adjuvant, such as IL-2 (claim 35-37, [0162]) and adjuvant can enhance or potentiate the immune responses. Regarding claim 81, it is noted that an optimum administration regimens for IL-2 may be obtained by routine experimentation, absent a showing of criticality or unexpected results.
Regarding claim 82, Heemskerk teaches that TCR T cells targeting SLLQHLGL can treat relapsed acute myeloid leukemia (AML) ([0409], [0484] and [0485]) which express high level of the PRAME peptide. Relapsed acute myeloid leukemia reads on a recurrent cancer. By combining teachings of Mata and Heemskerk, one of ordinary skill in the art would have been motivated to treat relapsed AML with αβ T cells, and/or γδ T cells expressing R11P3D3KE. Relapsed AML would be a good target for the engineered T cells, because it express high level of the PRAME peptide.
Regarding claim 85, Fig. 1 of Mata teaches activating T cells from a leukapheresis sample, transducing the activated T cells ex vivo with a lentiviral vector containing the genes encoding the TCR (also see [0048]). In addition, Mata teaches the method to produce autologous product ([0170]).
Regarding claims 86-88, Heemskerk teaches Lymphodepletion prior to T cell infusion with fludarabine 90 mg/m2 over 3 days with cyclophosphamide 750 mg/m2 ([0558-559]). Heemskerk teaches the lymphodepletion regimen is based on clinician assessment of their disease biology and comorbidities ([0553]).
Regarding claim 89, one ordinary skill in the art (e.g. a doctor) would be able to adjust dosage and application frequency to reach the claimed lymphodepletion regimen based on by routine experimentation, absent a showing of criticality or unexpected results.
Regarding claim 90, Mata teaches a method of preparing T cells for immunotherapy, including activating the T cells, transducing the activated T cells with the vector comprising the TCR, and expanding the transduced T cells ([0042], claims 1-5, and 27).
Regarding claim 91, Fig. 37 and [0216] of Mata teaches a T cell manufacturing process 370, which may include isolation of PBMC (371), in which PBMC may be used fresh or stored frozen till ready for use, or may be leukapheresis products, or may be used as starting materials for T cell manufacturing and selection of lymphocyte populations ( e.g., αβ TCR+ T cells, CD8+, CD4+, or both); thaw and rest lymphocytes overnight, e.g., about 16 hours or about 4-6 hours, (372), which may allow apoptotic cells to die off and restore T cell functionality (this step may not be necessary, if fresh materials are used); activation of lymphocytes (373), which may use anti-CD3 and anti-CD28 antibodies (soluble or surface bound, e.g., magnetic or biodegradable beads, antibodies immobilized on culture vessels); transduction with viral vectors containing sequences encoding recombinant proteins, e.g., CD8αβ and/or TCRαβ polypeptides (374), in which the viral vectors may be lentiviral vectors or retroviral vectors, or transfection may be performed by non-viral methods; and expansion of lymphocytes, harvest, and cryopreservation (375), which may be carried out in the presence of cytokine(s), e.g., IL-7 and IL-15, serum (ABS or FBS), and/or cryopreservation media.
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.
U.S. Patent No. 11,236,145 B2
Claims 76-91 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11,236,145 B2 (hereinafter Pat. 145, Appl. 15/928,785, cited in IDS of 02/28/2023) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
Claim 1 of Pat. 145 teaches an antigen recognizing construct comprising a T cell receptor (TCR) α chain comprising an α variable domain comprising CDR1α, CDR2α, and CDR3α of SEQ ID NO: 130, wherein the sequence of the α variable domain is at least 95% identical to SEQ ID NO: 130, and a TCR β chain comprising a β variable domain comprising CDR1β, CDR2β, and CDR3β of SEQ ID NO: 136, wherein the sequence of the β variable domain is at least 95% identical to SEQ ID NO: 136, wherein the antigen recognizing construct is capable of binding to a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 97) in a complex with HLA-A*02.
Claim 18 of Pat. 145 teaches The antigen recognizing construct of claim 1, comprising the TCR α chain comprising the amino acid sequence SEQ ID NO: 132 and
the TCR β chain comprising the amino acid sequence of SEQ ID NO: 138. As shown below SEQ ID NO: 132 and SEQ ID NO: 138 comprise SEQ ID NO: 113 and SEQ ID NO: 119 of the instant application.
Alignment of SEQ ID NO: 132 of Pat. 145 to SEQ ID NO: 113 of instant application:
Query Match 100.0%; Score 1427; Length 273;
Best Local Similarity 100.0%;
Matches 273; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
Qy 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
Qy 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
|||||||||||||||||||||||||||||||||
Db 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
Alignment of SEQ ID NO: 138 of Pat. 145 to SEQ ID NO: 119 of instant application:
Query Match 100.0%; Score 1654; Length 311;
Best Local Similarity 100.0%;
Matches 311; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
Qy 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
Qy 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
Qy 301 MAMVKRKDSRG 311
|||||||||||
Db 301 MAMVKRKDSRG 311
Thus, the claims of Pat. 145 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE.
The claims of Pat. 145 teach a host cell comprising the TCR (claim 8), and wherein the host cell is a CD4-positive or CD8-positive T cell (claim 20).
The claims of Pat. 145 teach a pharmaceutical composition comprising the engineered TCR T cells (claim 21).
The claims of Pat. 145 teach a nucleic acid or two separate nucleic acids encoding the antigen recognizing construct according to claim 18 (claim 24).
Taken together, the claims of Pat. 145 teach TCR T cells expressing the alpha chain and beta chain of instantly claimed. However, the claims of Pat. 145 do not teach treating cancers with the TCR T cells, or the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Pat. 145. Heemskerk teaches methods for treating cancers (including recurrent cancers) with TCR targeting PRAME-derived peptide SLLQHLIGL. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Pat. 145, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Pat. 145 which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including melanoma, lung cancer…) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including melanoma and lung cancer and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Pat. 145 for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Pat. 145 would be able to induce immune response against cancers expressing SLLQHLGL in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 79-91, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Pat. 145 based on the teachings of Mata and Heemskerk to a subject to treat a PRAME positive cancer with a reasonable expectation of success.
U.S. Patent No. 10,800,832 B2
Claims 76-91 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,800,832 B2 (hereinafter Pat. 832, Appl. 16/403,038, cited in IDS of 11/08/2022) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
Claim 5 of the Pat. 832 teaches a method of treating a patient who has a PRAME positive cancer, comprising administering to the patient a population of transformed CD8+ T cells expressing at least one vector encoding a T cell receptor (TCR), wherein the TCR comprises a CDR1α chain comprising the amino acid sequence of SEQ ID NO: 1, a CDR2α chain comprising the amino acid sequence of SEQ ID NO: 2, a CDR3α chain comprising the amino acid sequence of SEQ ID NO: 3,
a CDR1β chain comprising the amino acid sequences of SEQ ID NO: 7, a CDR2β chain comprising the amino acid sequence of SEQ ID NO: 8, and a CDR3β chain comprising the amino acid sequence of SEQ ID NO: 9, wherein the TCR is capable of binding to a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 97) in a complex with HLA-A*02, and wherein the cancer is selected from …, brain cancer, breast cancer, …, liver cancer, lung cancer, malignant mesothelioma, melanoma, multiple myeloma, …, and urinary bladder cancer. As evidenced by Table 1 of the specification of Pat. 832, SEQ ID NO: 1-3 are CDRs 1-3 of R11P3D3 alpha chain, and SEQ ID NO: 7-9 are CDRs 1-3 of R11P3D3 beta chain. These CDRs are identical to the CDRs recited by the instant claim 76.
The claims of Pat. 832 teaches the method of claim 1, wherein the population of transformed cells are produced by a method comprising isolating a cell from a subject,
transforming the cell with at least one vector encoding the TCR to produce transformed cell, and expanding the transformed cell to produce the population of transformed cells (claim 2), wherein the subject is the patient (claim 3).
Taken together, the claims of Pat. 832 teach treating cancers with engineered TCR T cells expressing the alpha chain and beta chain of instantly claimed. However, the claims of Pat. 832 do not teach treating the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells, or the full length alpha chain and beta chain.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same CDRs of Pat. 832. Heemskerk teaches methods for treating cancers (including recurrent cancers) with TCR targeting PRAME-derived peptide SLLQHLIGL. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Pat. 832, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Pat. 832 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including melanoma, lung cancer…) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including melanoma and lung cancer and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Pat. 832 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Pat. 832 and Mata would be able to induce immune response against cancers expressing SLLQHLGL in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 79-91, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Pat. 832 based on the teachings of Mata and Heemskerk to a subject to treat a PRAME positive cancer with a reasonable expectation of success.
U.S. Patent No. 11,111,286 B2
Claims 76-91 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,111,286 B2 (hereinafter Pat. 286, Appl. 16/731,139, cited in IDS of 11/08/2022) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
It is noted that Pat. 286 and Pat. 145 share the same disclosure, thus, the same SEQ ID NO would have same sequences.
Claim 1 of Pat. 286 teaches a method of treating a patient who has a PRAME positive cancer, wherein the PRAME positive cancer is capable of presenting a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 97) in the context of HLA-A*02 on the cell surface, comprising administering to the patient a population of transformed CD8+T cells expressing at least one vector encoding a T cell receptor (TCR), wherein the TCR comprises an α variable domain comprising CDR1α, CDR2α, and CDR3α of SEQ ID NO: 130, wherein the sequence of the α variable domain is at least 95% identical to SEQ ID NO:130, and a β variable domain comprising CDR1β, CDR2β, and CDR3β of SEQ ID NO: 136, wherein the sequence of the β variable domain is at least 95% identical to SEQ ID NO:136, wherein the TCR is capable of binding to a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 97) in a complex with HLA-A*02, and wherein the cancer is selected from …, and urinary bladder cancer.
Claim 1 of Pat. 286 teaches that the TCR comprises an α chain comprising the amino acid sequence SEQ ID NO: 132 and a β chain comprising the amino acid sequence of SEQ ID NO: 138. As shown in above (Pat. 145 rejection), SEQ ID NO: 132 and SEQ ID NO: 138 comprise SEQ ID NO: 113 and SEQ ID NO: 119 of the instant application. Thus, the claims of Pat. 286 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE.
Taken together, the claims of Pat. 286 teach treating cancers with engineered TCR T cells expressing the alpha chain and beta chain of instantly claimed. However, the claims of Pat. 286 do not teach treating the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same CDRs of Pat. 286. Heemskerk teaches methods for treating cancers (including recurrent cancers) with TCR targeting PRAME-derived peptide SLLQHLIGL. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Pat. 832, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Pat. 286 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including melanoma, lung cancer…) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including melanoma and lung cancer and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Pat. 286 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Pat. 286 and Mata would be able to induce immune response against cancers expressing SLLQHLGL in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 79-91, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Pat. 286 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
Application No. 17/553,017
Claims 76-91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 9-35 of copending Application No. 17/553,017 (hereinafter Appl. 017) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
It is noted that Pat. 145 and Appl. 017 share the same disclosure, thus, the same SEQ ID NO would have same sequences.
The claims of Appl. 017 teach a T cell receptor (TCR), comprising a complementarity determining region (CDR)1α comprising the amino acid sequence of SEQ ID NO: 1,a CDR2α comprising the amino acid sequence of SEQ ID NO: 196, a CDR3α comprising the amino acid sequence of SEQ ID NO: 3, a CDR1β comprising the amino acid sequence of SEQ ID NO: 7,a CDR2β comprising the amino acid sequence of SEQ ID NO: 8, and a CDR3β comprising the amino acid sequence of SEQ ID NO: 9 wherein said TCR is capable of binding to a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 97) in a complex with HLA-A*02 (claim 1); and a TCR comprising a TCR α chain as comprised in SEQ ID NO: 132; and a TCR β chain as comprised in SEQ ID NO: 138 (claim 21). As shown in above (Pat. 145 rejection), SEQ ID NO: 132 and SEQ ID NO: 138 comprise SEQ ID NO: 113 and SEQ ID NO: 119 of the instant application. Thus, the claims of Appl. 017 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE.
The claims of Appl. 017 teach a method of treating a patient who has a PRAME positive cancer, comprising administering the patient a population of T cells expressing the TCR according to claim 1 (claim 15), wherein the T cells comprises CD8+ T cells and/or CD4+ T cells (claim 24), wherein the T cells are autologous to the patient (claim 26).
The claims of Appl. 017 teach wherein the cancers can be breast cancer, lung cancer, bladder cancer (claim 34)
Taken together, the claims of Appl. 017 teach treating cancers with engineered TCR T cells expressing the alpha chain and beta chain of instantly claimed. However, the claims of Appl. 017 do not teach treating the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same CDRs of Appl. 017. Heemskerk teaches methods for treating cancers (including recurrent cancers) with TCR targeting PRAME-derived peptide SLLQHLIGL. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 017, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 017 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including melanoma, lung cancer…) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including melanoma and lung cancer and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 017 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 017 and Mata would be able to induce immune response against cancers expressing SLLQHLGL in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 79-91, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 017 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Application No. 17/938,577
Claims 76-91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-22, 24-60 of copending Application No. 17/938,577 (hereinafter Appl. 577) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
The claims of Appl. 577 teach a T cell receptor, or a functional fragment thereof, that is reactive with, or binds to, an WIC ligand, wherein said ligand is the peptide of SLLQHLIGL, for use in the (manufacture of a medicament for the) treatment of a patient (i) being diagnosed for, (ii) suffering from, or (iii) being at risk of developing, metastasis or a metastatic lesion (claim 5); and a nucleic acid encoding for the TCR of claim 5 (claim 7).
The claims of Appl. 577 teach a recombinant T cell comprising the TCR (claim 9), and wherein the TCR receptor comprises … (8) an alpha chain comprising SEQ ID NO: 111 and a beta chain comprising SEQ ID NO: 117, wherein the T cell receptor is capable of binding to a peptide consisting of the amino acid sequence of SLLQHLIGL (SEQ ID NO: 310) in a complex with HLA-A*02 (claim 11). As shown below SEQ ID NO: 111 and SEQ ID NO: 117 of Appl. 577 comprise SEQ ID NO: 111 and SEQ ID NO: 117 of the instant application.
Alignment of SEQ ID NO: 111 of Appl. 577 to SEQ ID NO: 111 of instant application:
Query Match 100.0%; Score 702; Length 132;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKP 132
||||||||||||
Db 121 RFGAGTRLTVKP 132
Alignment of SEQ ID NO: 117 of Appl. 577 to SEQ ID NO: 111 of instant application:
Query Match 100.0%; Score 710; Length 132;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVL 132
||||||||||||
Db 121 QYFGPGTRLTVL 132
Thus, the claims of Appl. 577 teach a TCR which reads on the TCR of instant claims 76 and 77.
The claims of Appl. 577 teach a method of treating a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on a cell surface, comprising: selecting a patient having a metastatic lesion and administering to the patient a composition comprising the recombinant T cell of claim 9, wherein the metastasis or metastatic lesion originates from a cancer selected from the group consisting of …, lung cancer, …, skin cutaneous melanoma, …, triple-negative breast cancer, …, and extranodal T/NK-cell lymphomas (claim 24).
The claims of Appl. 577 teach the method of claim 24 further administering to the patient at least one adjuvant including IL-2 (claim 26).
The claims of Appl. 577 teach a method of preparing a T cell population comprising: obtaining a T cell population from PBMCs; activating the obtained T cell population, transducing the activated T cell population with the nucleic acid of claim 7, expanding the transduced T cell population, and wherein activating, transducing, expanding, or combinations thereof are performed in the presence of IL-21 (claim 27).
The claims of Appl. 577 teach as set forth above. However, the claims of Appl. 577 do not teach treating the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells, or the full length alpha chain and beta chain.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same CDRs of Appl. 577. Heemskerk teaches methods for treating cancers (including recurrent cancers) with TCR targeting PRAME-derived peptide SLLQHLIGL. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 577, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 577 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including melanoma, lung cancer…) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including melanoma and lung cancer and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 577 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 577 and Mata would be able to induce immune response against cancers expressing SLLQHLGL in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 79-91, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 577 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Application No. 18/505,361
Claims 76-91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/505,361 (hereinafter Appl. 361) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
It is noted that Appl. 577 and Appl. 361 share the same disclosure, thus, the same SEQ ID NO would have same sequences.
The claims of Appl. 361 teach a method of treating a patient (or eliciting an immune response in a patient) who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface, comprising identifying a metastatic lesion and treating the metastatic lesion with a population of T lymphocytes that kills the metastasis or metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface, wherein the population of T lymphocytes comprises a T cell receptor (TCR) that binds a peptide comprising SLLQHLIGL (SEQ ID NO: 310) in a complex with a class I MHC molecule, …, wherein the metastasis or metastatic lesion originates from a cancer selected from the group consisting of …, lung cancer, …, melanoma, and extranodal T/NK-cell lymphomas (claims 1 and 2).
The claims of Appl. 361 teach the population of T lymphocyte is autologous or allogenic to the patient (claim 3).
The claims of Appl. 361 teach the TCR has an α chain variable domain comprising SEQ ID NO: 111, and a β chain variable domain comprising SEQ ID NO: 117 (claims 4 and 13). As shown above (in Appl. 577 rejection) SEQ ID NO: 111 and SEQ ID NO: 117 of Appl. 361 comprise SEQ ID NO: 111 and SEQ ID NO: 117 of the instant application.
The claims of Appl. 361 teach as set forth above. However, the claims of Appl. 577 do not teach treating the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells, or the full length alpha chain and beta chain.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same CDRs of Appl. 361. Heemskerk teaches methods for treating cancers (including recurrent cancers) with TCR targeting PRAME-derived peptide SLLQHLIGL. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 361, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 361 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including melanoma, lung cancer…) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including melanoma and lung cancer and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 361 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 361 and Mata would be able to induce immune response against cancers expressing SLLQHLGL in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 79-91, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 361 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Application No. 18/308,427
Claims 76-91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2-21 of copending Application No. 18/308,427 (hereinafter Appl. 427) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
The claims of Appl. 427 teach a T cell and/or NK cell transduced with a nucleic acid encoding (i) a polypeptide of SEQ ID NO: 311…..; or any combination of (i), (ii), (iii), and (iv) (claim 17); and a composition comprising the T cell and/or NK cell of claim 17 (claim 18); the composition further comprising an adjuvant such as IL-2 (claim 19).
The claims of Appl. 427 teach a T cell and/or NK cell of claim 17, comprising a nucleic acid comprising N1, N2, N3, N4, N5, L1, L2, L3, and L4, wherein N1 encodes a CD8β chain and is present or absent, …, N2 encodes a CD8α chain, …, N3 encodes a TCRβ chain, N4 encodes a TCRα chain, wherein N4 and N3 encode SEQ ID NO: 15 and 16, …, and N5 encodes at least one interleukin; …(claim 10). As shown below SEQ ID NO: 15 and SEQ ID NO: 16 comprise SEQ ID NO: 113 and SEQ ID NO: 119 (α chain and β chain of R11P3D3KE) of the instant application.
Alignment of SEQ ID NO: 15 of Appl. 427 to SEQ ID NO: 113 of instant application:
Query Match 100.0%; Score 1427; Length 273;
Best Local Similarity 100.0%;
Matches 273; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
Qy 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
Qy 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
|||||||||||||||||||||||||||||||||
Db 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
Alignment of SEQ ID NO: 16 of Appl. 427 to SEQ ID NO: 119 of instant application:
Query Match 100.0%; Score 1654; Length 311;
Best Local Similarity 100.0%;
Matches 311; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
Qy 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
Qy 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
Qy 301 MAMVKRKDSRG 311
|||||||||||
Db 301 MAMVKRKDSRG 311
Thus, the claims of Appl. 427 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE.
The claims of Appl. 427 teach a method of treating and/or eliciting an immune response in a patient who has cancer, comprising administering to the patient the composition of claim 18, wherein the cancer is selected from the group consisting of non-small cell lung cancer, small cell lung cancer, melanoma, liver cancer, breast cancer, uterine cancer, Merkel cell carcinoma, pancreatic cancer, gallbladder cancer, bile duct cancer, colorectal cancer, urinary bladder cancer, kidney cancer, leukemia, ovarian cancer, esophageal cancer, brain cancer, gastric cancer, and prostate cancer (claim 20).
The claims of Appl. 427 teach TCR T cells expressing the alpha chain and beta chain of instantly claimed and methods of treating cancers with the T cells. However, the claims of Appl. 427 do not teach the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Appl. 427. Heemskerk teaches methods for treating cancers (including recurrent cancers) with TCR targeting PRAME-derived peptide SLLQHLIGL. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 427, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 427 which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including melanoma, lung cancer…) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including melanoma and lung cancer and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 427 for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl.427 would be able to induce immune response against cancers expressing SLLQHLGL in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 79-91, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 427 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Application No. 18/309,062
Claims 76-91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11-13, 17-19, and 21-25 of copending Application No. 18/309,062 (hereinafter Appl. 062) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
The claims of Appl. 062 teach a nucleic acid encoding a polypeptide comprising (i) a sequence at least about 95% identical to SEQ ID NO: 305; (ii) a sequence at least about 95% identical to SEQ ID NO: 307; or (iii) both (i) and (ii) (claim 1).
The claims of Appl. 062 teach the nucleic acid of claim 1, further comprising a nucleic acid sequence encoding at least one TCR polypeptide, at least one CD8 polypeptide, or at least one TCR polypeptide and at least one CD8 polypeptide (claim 3).
The claims of Appl. 062 teach the nucleic acid of claim 3, wherein the TCR α chain and the TCR β chain are selected from SEQ ID NO: 15 and 16, …, in particular wherein the TCR α chain and the TCR β chain are selected from SEQ ID NO: 15 and 16, …; wherein the CD8α chain is SEQ ID NO: 7, 258, 259, 262, or a variant thereof; wherein the CD8β chain is SEQ ID NO: 8, 9, 10, 11, 12, 13, or 14 (claim 5). As shown below SEQ ID NO: 15 and SEQ ID NO: 16 comprise SEQ ID NO: 113 and SEQ ID NO: 119 (α chain and β chain of R11P3D3KE) of the instant application.
Alignment of SEQ ID NO: 15 of Appl. 062 to SEQ ID NO: 113 of instant application:
Query Match 100.0%; Score 1427; Length 273;
Best Local Similarity 100.0%;
Matches 273; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
Qy 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
Qy 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
|||||||||||||||||||||||||||||||||
Db 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
Alignment of SEQ ID NO: 16 of Appl. 062 to SEQ ID NO: 119 of instant application:
Query Match 100.0%; Score 1654; Length 311;
Best Local Similarity 100.0%;
Matches 311; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
Qy 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
Qy 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
Qy 301 MAMVKRKDSRG 311
|||||||||||
Db 301 MAMVKRKDSRG 311
Thus, the claims of Appl. 062 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE.
The claims of Appl. 062 teach a T cell and/or natural killer (NK) cell transduced with the nucleic acid of claim 1 (claim 17); a composition comprising the T cell and/or natural killer (NK) cell of claim 17 (claim 18); the composition of claim 18 can further comprise an adjuvant such as IL-2 (claim 19).
The claims of Appl. 062 teach TCR T cells expressing the alpha chain and beta chain of instantly claimed. However, the claims of Appl. 062 do not teach treating cancers with the TCR T cells, or the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Appl. 062. Heemskerk teaches methods for treating cancers (including recurrent cancers) with TCR targeting PRAME-derived peptide SLLQHLIGL. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 062, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 062 which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including melanoma, lung cancer…) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including melanoma and lung cancer and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 062 for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 062 would be able to induce immune response against cancers expressing SLLQHLGL in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 79-91, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 062 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Application No. 18/309,080
Claims 76-91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/309,080 (hereinafter Appl. 080) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
The claims of Appl. 080 teach a nucleic acid encoding a polypeptide comprising SEQ ID NO: 311, 313, or 315 or a polypeptide at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to SEQ ID NO: 311, 313, or 315, said nucleic acid optionally comprising SEQ ID NO: 312, 314, or 316 or a sequence at least about 80%, at least about 85%, at least about 90%, at least about 95%,at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to SEQ ID NO: 312, 314, or 316 (claim 1); the nucleic acid encoding a polypeptide comprising SEQ ID NO: 317, 321, 325, 327, 329, 331, or 333 or a polypeptide at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% identical to SEQ ID NO: 317, 321, 325,327, 329, 331, or 333 (claim 3).
The claims of Appl. 080 teach the nucleic acid further comprising a nucleic acid encoding (a) at least one TCR polypeptide comprising an α chain and a β chain, (b) at least one CD8 polypeptide comprising (i) an α chain, (ii) a β chain, or (iii) both an α chain and a β chain, or (c) at least one TCR polypeptide comprising an α chain and a β chain and at least one CD8 polypeptide comprising (i) an α chain, (ii) a β chain, or (iii) both an α chain and a β chain (claim 7).
The claims of Appl. 080 teach the nucleic acid of claim 7 wherein the TCR α chain and the TCR β chain are selected from SEQ ID NO: 15 and 16, …; and wherein if present, the CD8β chain is …(claim 9). As shown below SEQ ID NO: 15 and SEQ ID NO: 16 comprise SEQ ID NO: 113 and SEQ ID NO: 119 (α chain and β chain of R11P3D3KE) of the instant application.
Alignment of SEQ ID NO: 15 of Appl. 080 to SEQ ID NO: 113 of instant application:
Query Match 100.0%; Score 1427; Length 273;
Best Local Similarity 100.0%;
Matches 273; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 RFGAGTRLTVKPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKT 180
Qy 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VLDMRSMDFKSNSAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDT 240
Qy 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
|||||||||||||||||||||||||||||||||
Db 241 NLNFQNLSVIGFRILLLKVAGFNLLMTLRLWSS 273
Alignment of SEQ ID NO: 16 of Appl. 080 to SEQ ID NO: 119 of instant application:
Query Match 100.0%; Score 1654; Length 311;
Best Local Similarity 100.0%;
Matches 311; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRETMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QYFGPGTRLTVLEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVN 180
Qy 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GKEVHSGVSTDPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDE 240
Qy 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 WTQDRAKPVTQIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVL 300
Qy 301 MAMVKRKDSRG 311
|||||||||||
Db 301 MAMVKRKDSRG 311
Thus, the claims of Appl. 080 teach a TCR which has the same alpha chain and beta chain of R11P3D3KE.
The claims of Appl. 080 teach a T cell and/or natural killer cell transduced with the nucleic acid of claim 3 (claim 14); wherein the T cell and/or natural killer cell of claim 14, wherein the T cell is an αβ T cell, a γδ T cell, a natural killer T cell, or any combination thereof (claim 15); a composition comprising the T cell and/or NK cell of claim 14 (claim 16); the composition further comprising an adjuvant such as IL-2 (claims 17-19).
The claims of Appl. 080 teach a method of treating and/or eliciting an immune response in a patient who has cancer, comprising administering to the patient the composition of claim 16, wherein the cancer is selected from the group consisting of non-small cell lung cancer, small cell lung cancer, melanoma, liver cancer, breast cancer, uterine cancer, Merkel cell carcinoma, pancreatic cancer, gallbladder cancer, bile duct cancer, colorectal cancer, urinary bladder cancer, kidney cancer, leukemia, ovarian cancer, esophageal cancer, brain cancer, gastric cancer, and prostate cancer (claim 20).
Taken together, the claims of Appl. 080 teach TCR T cells expressing the alpha chain and beta chain of instantly claimed and methods of treating cancers with the T cells (such as αβ T cells, and/or γδ T cells). However, the claims of Appl. 080 do not teach the T cells are αβ T cells, and/or γδ T cells, or the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same alpha chain and beta chain of Appl. 080. Heemskerk teaches methods for treating cancers (including recurrent cancers) with TCR targeting PRAME-derived peptide SLLQHLIGL. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 080, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 080 which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including melanoma, lung cancer…) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including melanoma and lung cancer and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 080 for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 080 would be able to induce immune response against cancers expressing SLLQHLGL in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 79-91, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 080 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Application No. 19/020,283
Claims 76-91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of copending Application No. 19/020,283 (hereinafter Appl. 283) in view of Mata (Mata et al., US 2020/0376031 A1, Publication Date: 12/03/2020, cited in IDS of 02/28/2023) in view of Heemskerk (Heemskerk et al., US 2016/0263155, Publication Date: 09/15/2016, cited in IDS of 02/28/2023).
The claims of Appl. 283 teach a nucleic acid comprising a nucleic acid sequence encoding: (i) a T-cell receptor (TCR) comprising a TCR α chain and a TCR β chain; and (ii) a CD8 polypeptide comprising an amino acid sequence which is at least 95% identical to SEQ ID NO: 5, 258, 259, 262, or a variant thereof (claim 1), a polypeptide encoded by the nucleic acid of claim 1 (claim 4).
The claims of Appl. 283 teach the TCR α chain and the TCR β chain can be SEQ ID NO: 71 and SEQ ID NO: 303 (claim 2). As evidenced by the Table 3 of the specification, the SEQ ID NO: 71 and SEQ ID NO: 303 are the α chain and the β chain of R11P3D3_KE. Thus, the TCR of Appl. 283 reads on the TCR of instant claims 76-78.
The claims of Appl. 283 teach a T cell transduced with the nucleic acid of claim 1 (claim 17), wherein the T cell is an αβ T cell and/or γδ T cell (claim 18).
The claims of Appl. 283 teach a T cell expressing the polypeptide of claim 4 (claim 21), a composition comprising the T cell of claim 21 (claim 23).
The claims of Appl. 283 teach a method of preparing T cells for immunotherapy comprising isolating T cells from a blood sample of a human subject, activating the isolated T cells, transducing the activated T cells with the nucleic acid of claim 1, and expanding the transduced T cells (claim 26).
The claims of Appl. 283 teach a method of treating a patient who has cancer, comprising administering to the patient the composition of claim 23, wherein the cancer is selected from the group consisting of non-small cell lung cancer, small cell lung cancer, melanoma, liver cancer, breast cancer, uterine cancer, Merkel cell carcinoma, pancreatic cancer, gallbladder cancer, bile duct cancer, colorectal cancer, urinary bladder cancer, kidney cancer, leukemia, ovarian cancer, esophageal cancer, brain cancer, gastric cancer, and prostate cancer (claim 27).
The claims of Appl. 283 teach as set forth above. However, the claims of Appl. 283 do not teach treating the dose range for the T cells.
Mata and Heemskerk teach as set forth above. In particular, Mata teaches a method of treating a cancer with engineered αβ T cells, and/or γδ T cells comprising a TCR such as R11P3D3KE which recognize the PRAME-derived peptide SLLQHLIGL and comprised the same CDRs of Appl. 283. Heemskerk teaches methods for treating cancers (including recurrent cancers) with TCR targeting PRAME-derived peptide SLLQHLIGL. Heemskerk teaches the dose range of the TCR T cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 283, Mata and Heemskerk and treat a patient with cancer that presents a peptide comprising SLLQHLIGL by inducing an immune response with engineered αβ T cells, and/or γδ T cells expressing the TCR taught by the claims of Appl. 283 and Mata such as R11P3D3KE which would recognize SLLQHLIGL with a dosage about 3 x 108 cells because Mata teaches treating cancers (including melanoma, lung cancer…) with said TCR T cells and the T-cells recognize the cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including melanoma and lung cancer and dosage for the T cells (see [0006] of Heemskerk). One would have been motivated to use the T cells expressing TCRs of Appl. 283 and Mata for treatment of cancers that express a PRAME peptide (e.g. SLLQHLGL) because these cancers would be targeted by the T cells expressing the TCR. Based on the antigen-dependent activity of T cells comprising R11P3D3KE in vitro (shown by Mata), one of ordinary skill in the art would have had a reasonable expectation of success that αβ T cells, and/or γδ T cells comprising the TCR of Appl. 283 and Mata would be able to induce immune response against cancers expressing SLLQHLGL in vivo.
It is also noted that optimum suitable ranges may be obtained by routine experimentation, absent a showing of criticality or unexpected results. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Regarding claims 79-91, Mata and Heemskerk teach the recited limitations as set forth in 103 rejections. It would have been obvious to the skilled artisan at the time of filing to prepare and administer the engineered TCR T cells comprising the TCR recited in the Appl. 283 to a subject based on the teachings of Mata and Heemskerk to treat a PRAME positive cancer with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/CHENG LU/ Examiner, Art Unit 1642