DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
1. Claims 1-40 as amended on March 16, 2026 are pending and under consideration. Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
2. 37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). See p. 46-¶ [0234], line 4.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
3. 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).
SEQ ID NOs 13, 25, 37, 49, 73, 85, 97, and 109 are less than 4 amino acids. 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 should be deleted and replaced with the amino acid sequence that they represent as long as support is found in the specification as filed. See e.g. ¶¶ [0202] and Table 15. .
Appropriate correction is required.
Claim Objections
4. Claims 1 and 2 are objected to because of the following informalities: Claims 1 and 2 contain CDR sequences of SEQ ID NOs 13, 25, 37, 49, 73, or 85 which are sequences are less than 4 amino acid sequences. These sequences are replaced with “000” in the Sequence Listing in XML because the sequences are less than 4 amino acid sequences in length. See 37 CFR § 1.831(j). The CDR sequences of SEQ ID NOs 13, 25, 37, 49, 73, or 85 should be deleted and replaced with the amino acid sequence that they represent as long as support is found in the specification as filed. Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
5. Claim(s) 1-31, 33-37, 39 and 40 are rejected under 35 U.S.C. 103 as being unpatentable over US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten” in view of US 2016/0263155 A1 (Heemskerk et al. Sep. 15, 2016,ids ), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert”.
Alten teaches a method of treating a patient who has 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 SEQ ID NOs: 1, 3, 7, and 9, or SEQ ID NOs: 13, 15, 19, and 21, or SEQ ID NOs: 25, 27, 31, and 33, or SEQ ID NOs: 37, 39, 43, and 45, or SEQ ID NOs: 49, 51, 55, and 57, or SEQ ID NOs: 61, 63, 67, and 69, or SEQ ID NOs: 73, 75, 79, and 81, or SEQ ID NOs: 127, 129, 133, and 135, wherein each of SEQ ID NOs: 1, 3, 7, 9, 13, 15, 19, 21, 25, 27, 31, 33, 37, 39, 43, 45, 49, 51, 55, 57, 61, 63, 67, 69, 73, 75, 79, 81, 127, 129, 133, and 135 comprises at most one conservative amino acid substitution, 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 an MHC class I molecule, and wherein the cancer is selected from acute lymphocytic cancer, acute myeloid leukemia, alveolar rhabdomyosarcoma, bone cancer, brain cancer, breast cancer, cancer of the anus, anal canal, or anorectum, cancer of the eye, cancer of the intrahepatic bile duct, cancer of the joints, cancer of the neck, gallbladder, or pleura, cancer of the nose, nasal cavity, or middle ear, cancer of the oral cavity, cancer of the vagina, cancer of the vulva, chronic lymphocytic leukemia, chronic myeloid cancer, colon cancer, esophageal cancer, cervical cancer, gastrointestinal carcinoid tumor, glioma, Hodgkin lymphoma, hypopharynx cancer, kidney cancer, larynx cancer, liver cancer, lung cancer, malignant mesothelioma, melanoma, multiple myeloma, nasopharynx cancer, non-Hodgkin lymphoma, cancer of the oropharynx, ovarian cancer, cancer of the penis, pancreatic cancer, peritoneum, omentum, and mesentery cancer, pharynx cancer, prostate cancer, rectal cancer, renal cancer, skin cancer, small intestine cancer, soft tissue cancer, stomach cancer, testicular cancer, thyroid cancer, cancer of the uterus, ureter cancer, and urinary bladder cancer. See claim 1.
Alten teaches the TCR comprises an α chain comprising the amino acid sequence of SEQ ID NO: 6 and a β chain comprising the amino acid sequence of SEQ ID NO: 12, or an α chain comprising the amino acid sequence of SEQ ID NO: 18 and β chain comprising the amino acid sequence of SEQ ID NO: 24, or an α chain comprising the amino acid sequence of SEQ ID NO: 30 and β chain comprising of the amino acid sequence of SEQ ID NO: 36, or an α chain comprising the amino acid sequence of SEQ ID NO: 42 and β chain comprising of the amino acid sequence of SEQ ID NO: 48, or an α chain comprising the amino acid sequence of SEQ ID NO: 54 and β chain comprising of the amino acid sequence of SEQ ID NO: 60, or an α chain comprising the amino acid sequence of SEQ ID NO: 66 and β chain comprising of the amino acid sequence of SEQ ID NO: 72, or an α chain comprising the amino acid sequence of SEQ ID NO: 78 and β chain comprising of the amino acid sequence of SEQ ID NO: 84, or an α chain comprising the amino acid sequence of SEQ ID NO: 132 and a β chain comprising of the amino acid sequence of SEQ ID NO: 138. See claim 5.
SEQ ID NOs: 6 and 12 of Alten comprise the claimed SEQ ID NOs:15 and 21. See Appendix.
SEQ ID NOs: 18 and 24 of Alten comprise the claimed SEQ ID NOs: 27 and 33. See Appendix.
SEQ ID NOs: 30 and 36 of Alten comprise the claimed SEQ ID NOs: 39 and 45. See Appendix.
SEQ ID NOs: 42 and 48 of Alten comprise the claimed SEQ ID NOs: 51 and 57. See Appendix.
SEQ ID NOs: 54 and 60 of Alten comprise the claimed SEQ ID NOs: 63 and 69. See Appendix.
SEQ ID NOs: 66 and 72 of Alten comprise the claimed SEQ ID NOs: 75 and 81. See Appendix.
SEQ ID NOs: 78 and 84 of Alten comprise the claimed SEQ ID NOs: 87 and 93. See Appendix.
SEQ ID NOs: 130 and 136 of Alten comprise the claimed SEQ ID NOs: 111 and 117. See Appendix.
SEQ ID NOs:132 and 138 of Alten comprise the claimed SEQ ID NOs: 113 and 119. See Appendix.
Alten teaches re-expression of the TCR R11P3D3 (SEQ ID Nos: 6 and 12) in human primary CD8+ T-cells leads to selective recognition and killing of HLA-A*02/PRAME-004-presenting tumor cell lines. See ¶ 0205 and FIGS. 24, 25, 30 and 32.
Alten teaches that the cells can be cells that are allogeneic or autologous to the mammal. See ¶ 0115.
Alten teaches that the T cells stimulate an immune response. See ¶¶ 0006, 0024, 0029, 0055, 0092 and 0126.
Alten teaches that the T cell is able to mediate an immune response against a target cell expressing the TAA of the invention, preferably presenting TAA peptides via MHC I or II on the surface of said target cell. See ¶¶ 0092.
Alten teaches expression of the TCRs from retroviral and lentiviral vectors for expression, isolation, and purification . See ¶¶ 0069-0086 and 0189-0199.
Alten teaches as set forth above, but does not teach treating a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface.
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. See abstract and ¶ 0003.
Heemskerk teaches treating melanoma and uveal melanoma with T cell receptors directed against PRAME. See ¶¶ 0006 and 0369.
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. See ¶¶ 0507, 1030.
Heemskerk teaches that human T cells transduced with the pSFG-iC9.2A.PRAME-derived Cell A vector engineered with the TCRs that recognize SLLQHLIGL are effective against tumors in vivo. See ¶¶ 0507-0511 and Figs. 4 and 6.
Heemskerk teaches treatment of metastasis and metastatic melanoma with the engineered T cells of the invention that recognize SLLQHLIGL. See ¶¶ 0038, 0055, 0109, 0307, 0369, and 0384.
Heemskerk teaches that the cells can be cells that are allogeneic or autologous T cells. See ¶ 0054.
Ulmert teaches PRAME is a cancer/testis antigen initially isolated from melanoma cells. PRAME has been shown to be overexpressed in an array of solid and hematological malignancies. In hematological malignancies, PRAME has displayed particularly high expression in Acute Myeloid Leukemia (AML), Acute Lymphoid Leukemia (ALL) and Chronic Myeloid Leukemia (CIVIL) in blast crisis (1, 2). Ulmert teaches among the prevalent solid tumors, PRAME is particularly highly expressed in ovarian carcinomas, endometrial carcinomas, squamous cell carcinomas of the lung, cutaneous melanomas and basal subtype breast cancer. Ulmert teaches PRAME expression has been associated with very poor prognosis and disease progression. See ¶ 0005. Ulmert teaches PRAME expression has been associated with very poor prognosis and disease progression.
Ulmert teaches PRAME plasma membrane localization allows it to be targeted for treatment. See ¶ 0006.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Alten, Heemskerk, and Ulmert and treat a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface by inducing an immune response with autologous or allogenic T cells expressing the TCRs of Alten which recognize SLLQHLIGL because Alten teaches treating a patient who has cancer, including melanomas and esophageal, skin, and anal cancer, with said T cells and the T-cells recognize and kill cells expressing the PRAME antigen, Heemskerk teaches that SLLQHLIGL is expressed in various cancer including metastatic melanoma and uveal melanoma and Ulmert teaches PRAME is expressed in numerous cancers like cutaneous, PRAME expression has been associated with very poor prognosis and disease progression and PRAME can be targeted for treatment. One would have been motivated to identify metastatic lesions that express SLLQHLIGL on the surface of the cells so that one would know that the metastatic cells were amenable to treatment with the with the T cells expressing the TCRs of Alten which recognize SLLQHLIGL.
6. Claim(s) 32 and 38 are rejected under 35 U.S.C. 103 as being unpatentable US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten” in view of US 2016/0263155 A1 (Heemskerk et al. Sep. 15, 2016, IDS), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert”, as applied to claims 1-31, 33-37, 39 and 40 above, and further in view of Toyama et al. (Modern Pathology Aug. 02, 2019 32: 1727-1733), “Toyama”.
Alten, Heemskerk, and Ulmert teach as set forth above, but do not teach treating a mucosal melanoma.
Toyama teaches that in mucosal melanoma the majority of melanomas expressed PRAME and high expression predicted poor prognosis. See abstract and Figs. 1-3.
Toyama teaches that PRAME is expressed in metastatic mucosal melanoma. See Suppl. Table 2.
Toyama teaches with the majority of mucosal melanomas in our study staining for PRAME, specifically targeting tumor cells with PRAME expression may be a strategy for future therapy of this devastating cancer, just as it has shown potential in cutaneous and uveal melanomas. See p. 1733-left column.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Alten, Heemskerk, Ulmert and Toyama and treat a patient who has mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of Alten which recognize SLLQHLIGL because Toyama teaches that in mucosal melanoma the majority of melanomas expressed PRAME and PRAME is expressed in metastatic mucosal melanoma. One would have been motivated to treat mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of Alten because Toyama teaches with the majority of mucosal melanomas in our study staining for PRAME, specifically targeting tumor cells with PRAME expression may be a strategy for therapy.
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
7. Claims 1-5, 12-14, 21-31, 33-37, 39 and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,800,832 (Alten et al. Oct. 13, 2020, IDS) in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten” , in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert”.
The ‘832 claims are drawn to:
1. 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 acute lymphocytic cancer, acute myeloid leukemia, alveolar rhabdomyosarcoma, bone cancer, brain cancer, breast cancer, cancer of the anus, anal canal, or anorectum, cancer of the eye, cancer of the intrahepatic bile duct, cancer of the joints, cancer of the neck, gallbladder, or pleura, cancer of the nose, nasal cavity, or middle ear, cancer of the oral cavity, cancer of the vagina, cancer of the vulva, chronic lymphocytic leukemia, chronic myeloid cancer, colon cancer, esophageal cancer, cervical cancer, gastrointestinal carcinoid tumor, glioma, Hodgkin lymphoma, hypopharynx cancer, kidney cancer, larynx cancer, liver cancer, lung cancer, malignant mesothelioma, melanoma, multiple myeloma, nasopharynx cancer, non-Hodgkin lymphoma, cancer of the oropharynx, ovarian cancer, cancer of the penis, pancreatic cancer, peritoneum, omentum, and mesentery cancer, pharynx cancer, prostate cancer, rectal cancer, renal cancer, skin cancer, small intestine cancer, soft tissue cancer, stomach cancer, testicular cancer, thyroid cancer, cancer of the uterus, ureter cancer, and urinary bladder cancer.
2. 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 a transformed cell, and expanding the transformed cell to produce the population of transformed cells.
3. The method of claim 2, wherein the subject is the patient.
4. The method of claim 2, wherein the subject is a healthy donor.
5. 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 an α chain comprising the amino acid sequence of SEQ ID NO: 6 and a β chain comprising the amino acid sequence of SEQ ID NO: 12, 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 acute lymphocytic cancer, acute myeloid leukemia, alveolar rhabdomyosarcoma, bone cancer, brain cancer, breast cancer, cancer of the anus, anal canal, or anorectum, cancer of the eye, cancer of the intrahepatic bile duct, cancer of the joints, cancer of the neck, gallbladder, or pleura, cancer of the nose, nasal cavity, or middle ear, cancer of the oral cavity, cancer of the vagina, cancer of the vulva, chronic lymphocytic leukemia, chronic myeloid cancer, colon cancer, esophageal cancer, cervical cancer, gastrointestinal carcinoid tumor, glioma, Hodgkin lymphoma, hypopharynx cancer, kidney cancer, larynx cancer, liver cancer, lung cancer, malignant mesothelioma, melanoma, multiple myeloma, nasopharynx cancer, non-Hodgkin lymphoma, cancer of the oropharynx, ovarian cancer, cancer of the penis, pancreatic cancer, peritoneum, omentum, and mesentery cancer, pharynx cancer, prostate cancer, rectal cancer, renal cancer, skin cancer, small intestine cancer, soft tissue cancer, stomach cancer, testicular cancer, thyroid cancer, cancer of the uterus, ureter cancer, and urinary bladder cancer.
6. The method of claim 1, wherein the population of transformed cells are administered in the form of a pharmaceutical composition.
7. The method of claim 6, wherein the pharmaceutical composition comprises a chemotherapeutic agent selected from the group consisting of asparaginase, busulfan, carboplatin, cisplatin, daunorubicin, doxorubicin, fluorouracil, gemcitabine, hydroxyurea, methotrexate, paclitaxel, rituximab, vinblastine, and vincristine.
8. The method of claim 1, 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 consisting of 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 consisting of the amino acid sequence of SEQ ID NO: 9.
9. The method of claim 1, wherein the TCR comprises: a CDR1α chain consisting of 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 consisting of 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.
10. The method of claim 1, wherein the TCR comprises a CDR1α chain consisting of the amino acid sequence of SEQ ID NO: 1, a CDR2α chain consisting of the amino acid sequence of SEQ ID NO: 2, a CDR3α chain consisting of the amino acid sequence of SEQ ID NO: 3, a CDR1β chain consisting of the amino acid sequence of SEQ ID NO: 7, a CDR2β chain consisting of the amino acid sequence of SEQ ID NO: 8, and a CDR3β chain consisting of the amino acid sequence of SEQ ID NO: 9.
11. The method of claim 1, wherein the cancer is melanoma.
12. The method of claim 1, wherein the cancer is bone cancer.
13. The method of claim 10, wherein the cancer is melanoma.
14. The method of claim 10, wherein the cancer is bone cancer.
SEQ ID NOs: 6 and 12 of the claims comprise the claimed SEQ ID NOs:15 and 21. SEQ ID NOs: 6 and 12 are 99% identical to SEQ ID NOs:111 and 113 and 117 and 119. See Appendix.
The ‘832 claims teach as set forth above, but do not teach treating a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface.
Alten, Heemskerk and Ulmert teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘832 claims, Alten, Heemskerk and Ulmert treat a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface by inducing an immune response with autologous or allogenic T cells expressing the TCRs of the ‘832 claims which recognize SLLQHLIGL because the ‘832 claims teach treating a patient who has cancer, including melanoma, with said T cells, Alten teaches treating a patient who has cancer, including melanomas and esophageal, skin, and anal cancer , with said T cells and the T-cells recognize and kill cells expressing the PRAME antigen, Heemskerk teaches that SLLQHLIGL is expressed in various cancer including metastatic melanoma and uveal melanoma and Ulmert teaches PRAME is expressed in numerous cancers like cutaneous, PRAME expression has been associated with very poor prognosis and disease progression and PRAME can be targeted for treatment. One would have been motivated to identify metastatic lesions that express SLLQHLIGL on the surface of the cells so that one would know that the metastatic cells were amenable to treatment with the with the T cells expressing the TCRs of the ‘832 claims which recognize SLLQHLIGL.
8. Claims 32 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,800,832 (Alten et al. Oct. 13, 2020, IDS), in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten”, in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert” as applied to claims 1-5, 12-14, 21-31, 33-37, 39 and 40 above, in further view of Toyama et al. (Modern Pathology Aug. 02, 2019 32: 1727-1733), “Toyama”.
The ‘832 claims, Alten, Heemskerk, and Ulmert teach as set forth above, but do not teach treating a mucosal melanoma.
Toyama teaches as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘832 claims, Alten, Heemskerk, Ulmert and Toyama and treat a patient who has mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘832 claims which recognize SLLQHLIGL because Toyama teaches that in mucosal melanoma the majority of melanomas expressed PRAME and PRAME is expressed in metastatic mucosal melanoma. One would have been motivated to treat mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘832 claims because Toyama teaches with the majority of mucosal melanomas in our study staining for PRAME, specifically targeting tumor cells with PRAME expression may be a strategy for therapy.
9. Claims 1-5, 12-14, 21-31, 33-37, 39 and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,111,286 (Alten et al. Sep. 7, 2021, IDS), in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten”, in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016, IDS ), “Heemskerk” in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert”.
The ‘286 claims are drawn to:
1. 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 acute lymphocytic cancer, acute myeloid leukemia, alveolar rhabdomyosarcoma, bone cancer, brain cancer, breast cancer, cancer of the anus, anal canal, or anorectum, cancer of the eye, cancer of the intrahepatic bile duct, cancer of the joints, cancer of the neck, gallbladder, or pleura, cancer of the nose, nasal cavity, or middle ear, cancer of the oral cavity, cancer of the vagina, cancer of the vulva, chronic lymphocytic leukemia, chronic myeloid cancer, colon cancer, esophageal cancer, cervical cancer, gastrointestinal carcinoid tumor, glioma, Hodgkin lymphoma, hypopharynx cancer, kidney cancer, larynx cancer, liver cancer, lung cancer, malignant mesothelioma, melanoma, multiple myeloma, nasopharynx cancer, non-Hodgkin lymphoma, cancer of the oropharynx, ovarian cancer, cancer of the penis, pancreatic cancer, peritoneum, omentum, and mesentery cancer, pharynx cancer, prostate cancer, rectal cancer, renal cancer, skin cancer, small intestine cancer, soft tissue cancer, stomach cancer, testicular cancer, thyroid cancer, cancer of the uterus, ureter cancer, and urinary bladder cancer.
2. The method of claim 1, wherein the population of transformed cells are produced by a method comprising isolating a CD8+T cell from a subject, transforming the cell with at least one vector encoding the TCR to produce a transformed cell, and expanding the transformed cell to produce the population of transformed cells.
3. The method of claim 2, wherein the subject is the patient.
4. The method of claim 2, wherein the subject is a healthy donor.
5. The method of claim 1, wherein the population of transformed cells are administered in the form of a pharmaceutical composition.
6. The method of claim 5, wherein the pharmaceutical composition comprises a chemotherapeutic agent selected from the group consisting of asparaginase, busulfan, carboplatin, cisplatin, daunorubicin, doxorubicin, fluorouracil, gemcitabine, hydroxyurea, methotrexate, paclitaxel, rituximab, vinblastine, and vincristine.
7. The method of claim 1, wherein the CDR1α consists of the amino acid sequence of SEQ ID NO: 127, the CDR2α comprises the amino acid sequence of SEQ ID NO: 128, the CDR3α comprises the amino acid sequence of SEQ ID NO: 129, the CDR1β consists of the amino acid sequences of SEQ ID NO: 133, the CDR2β comprises the amino acid sequence of SEQ ID NO: 134, and the CDR3β comprises the amino acid sequence of SEQ ID NO: 135.
8. The method of claim 1, wherein the CDR1α comprises the amino acid sequence of SEQ ID NO: 127, the CDR2α consists of the amino acid sequence of SEQ ID NO: 128, the CDR3α comprises the amino acid sequence of SEQ ID NO: 129, the CDR1β comprises the amino acid sequences of SEQ ID NO: 133, the CDR2β consists of the amino acid sequence of SEQ ID NO: 134, and the CDR3β comprises the amino acid sequence of SEQ ID NO: 135.
9. The method of claim 1, wherein the CDR1α comprises the amino acid sequence of SEQ ID NO: 127, the CDR2α comprises the amino acid sequence of SEQ ID NO: 128, the CDR3α consists of the amino acid sequence of SEQ ID NO: 129, the CDR1β comprises the amino acid sequences of SEQ ID NO: 133, the CDR2β comprises the amino acid sequence of SEQ ID NO: 134, and the CDR3β consists of the amino acid sequence of SEQ ID NO: 135.
10. The method of claim 1, wherein the CDR1α consists of the amino acid sequence of SEQ ID NO: 127, the CDR2α consists of the amino acid sequence of SEQ ID NO: 128, the CDR3α comprises the amino acid sequence of SEQ ID NO: 129, the CDR1β consists of the amino acid sequences of SEQ ID NO: 133, the CDR2β consists of the amino acid sequence of SEQ ID NO: 134, and the CDR3β comprises the amino acid sequence of SEQ ID NO: 135.
11. The method of claim 1, wherein the CDR1α consists of the amino acid sequence of SEQ ID NO: 127, the CDR2α comprises the amino acid sequence of SEQ ID NO: 128, the CDR3α consists of the amino acid sequence of SEQ ID NO: 129, the CDR1β consists of the amino acid sequences of SEQ ID NO: 133, the CDR2β comprises the amino acid sequence of SEQ ID NO: 134, and the CDR3β consists of the amino acid sequence of SEQ ID NO: 135.
12. The method of claim 1, wherein the CDR1α comprises the amino acid sequence of SEQ ID NO: 127, the CDR2α consists of the amino acid sequence of SEQ ID NO: 128, the CDR3α consists of the amino acid sequence of SEQ ID NO: 129, the CDR1β comprises the amino acid sequences of SEQ ID NO: 133, the CDR2β consists of the amino acid sequence of SEQ ID NO: 134, and the CDR3β consists of the amino acid sequence of SEQ ID NO: 135.
13. The method of claim 1, wherein the CDR1α consists of the amino acid sequence of SEQ ID NO: 127, the CDR2α consists of the amino acid sequence of SEQ ID NO: 128, the CDR3α consists of the amino acid sequence of SEQ ID NO: 129, the CDR1β consists of the amino acid sequences of SEQ ID NO: 133, the CDR2β consists of the amino acid sequence of SEQ ID NO: 134, and the CDR3β consists of the amino acid sequence of SEQ ID NO: 135.
14. The method of claim 1, wherein the cancer is melanoma.
15. The method of claim 1, wherein the cancer is bone cancer.
16. The method of claim 1, wherein the cancer is breast cancer.
17. The method of claim 1, wherein the cancer is lung cancer.
18. The method of claim 1, wherein the cancer is urinary bladder cancer.
19. The method of claim 1, wherein 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.
20. The method of claim 1, wherein the α variable domain comprises SEQ ID NO: 130 and the β, variable domain comprises SEQ ID NO: 136.
SEQ ID NOs: 132 and 138 of the ‘286 claims comprise the claimed SEQ ID NOs: 111 and 113 and 117 and 119. See Appendix. SEQ ID NOs: 132 and 138 of the ‘286 claims are 99% identical to SEQ ID NO: 15 and 21. See Appendix.
The ‘286 claims teach as set forth above, but do not teach treating a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface.
Alten, Heemskerk and Ulmert teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘286 claims, Alten, Heemskerk and Ulmert and treat a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface by inducing an immune response with autologous or allogenic T cells expressing the TCRs of the ‘286 claims which recognize SLLQHLIGL because the ‘286 claims teach treating a patient who has cancer, including melanoma, with said T cells, Alten teaches treating a patient who has cancer, including melanomas and esophageal, skin, and anal cancer , with said T cells and the T-cells recognize and kill cells expressing the PRAME antigen and Heemskerk teaches that SLLQHLIGL is expressed in various cancer including metastatic melanoma and uveal melanoma and Ulmert teaches PRAME is expressed in numerous cancers like cutaneous, PRAME expression has been associated with very poor prognosis and disease progression and PRAME can be targeted for treatment. One would have been motivated to identify metastatic lesions that express SLLQHLIGL on the surface of the cells so that one would know that the metastatic cells were amenable to treatment with the with the T cells expressing the TCRs of the ‘286 claims which recognize SLLQHLIGL.
10. Claims 32 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,111,286 (Alten et al. Sep. 7, 2021, IDS), in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten”, in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert” as applied to claims 1-5, 12-14, 21-31, 33-37, 39 and 40 above, in further view of Toyama et al. (Modern Pathology Aug. 02, 2019 32: 1727-1733), “Toyama”.
The ‘286 claims, Alten, Heemskerk, and Ulmert teach as set forth above, but do not teach treating a mucosal melanoma.
Toyama teaches as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘286 claims, Alten, Heemskerk, Ulmert and Toyama and treat a patient who has mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘286 claims which recognize SLLQHLIGL because Toyama teaches that in mucosal melanoma the majority of melanomas expressed PRAME and PRAME is expressed in metastatic mucosal melanoma. One would have been motivated to treat mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘286 claims because Toyama teaches with the majority of mucosal melanomas in our study staining for PRAME, specifically targeting tumor cells with PRAME expression may be a strategy for therapy.
11. Claims 1-5, 12-14, 21-31, 33-37, 39 and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11,236,145 (Alten et al. Feb. 1, 2022, IDS) in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten” and in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert”.
The ‘145 claims are drawn to:
1. 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.
2. The antigen recognizing construct according to claim 1, wherein the TCR α chain comprises a CDR3 consisting of the amino acid sequence SEQ ID NO: 129, and/or wherein the TCR β chain comprises a CDR3 consisting of the amino acid sequence SEQ ID NO: 135.
3. The antigen recognizing construct according to claim 2, wherein the TCR α chain further comprises a CDR1 consisting of the amino acid sequence SEQ ID NO: 127; and/or a CDR2 consisting of the amino acid sequence SEQ ID NO: 128.
4. The antigen recognizing construct according to claim 2, wherein the TCR β chain further comprises a CDR1 consisting of the amino acid sequence SEQ ID NO: 133; and/or a CDR2 consisting of the amino acid sequence SEQ ID NO: 134.
5. The antigen recognizing construct according to claim 1, wherein the α variable domain consists of the amino acid sequence SEQ ID NO: 130 and the β variable domain consists of the amino acid sequence SEQ ID NO: 136.
6. A nucleic acid encoding for an antigen recognizing construct according to claim 1.
7. A vector comprising a nucleic acid according to claim 6.
8. A host cell comprising an antigen recognizing construct according to claim 1, or a nucleic acid encoding for said antigen recognizing construct, or a vector comprising said nucleic acid.
9. A pharmaceutical composition comprising (i) the antigen recognizing construct according to claim 1, or (ii) a nucleic acid encoding for said antigen recognizing construct, or (iii) a vector comprising said nucleic acid, or (iv) a host cell comprising said antigen recognizing construct, a nucleic acid encoding for said antigen recognizing construct, or a vector comprising said nucleic acid, and a pharmaceutical acceptable carrier, stabilizer and/or excipient.
10. A method of manufacturing a tumor associated antigen (TAA) specific antigen recognizing construct expressing cell line, comprising a. providing a suitable host cell, b. providing a genetic construct comprising a coding sequence encoding the antigen recognizing construct according to claim 1, c. introducing into said suitable host cell said genetic construct, and d. expressing said genetic construct by said suitable host cell.
11. The method according to claim 10, further comprising isolation and purification of the antigen recognizing construct from the suitable host cell.
12. The antigen recognizing construct of claim 1, comprising the CDR1α comprising the amino acid sequence of SEQ ID NO: 127, the CDR2α comprising the amino acid sequence of SEQ ID NO: 128, the CDR3α comprising the amino acid sequence of SEQ ID NO: 129, the CDR1β comprising the amino acid sequence of SEQ ID NO: 133, the CDR2β comprising the amino acid sequence of SEQ ID NO: 134, and the CDR3β comprising the amino acid sequence of SEQ ID NO: 135.
13. The antigen recognizing construct of claim 1, comprising the CDR1α consisting of the amino acid sequence of SEQ ID NO: 127, the CDR2α comprising the amino acid sequence of SEQ ID NO: 128, the CDR3α comprising the amino acid sequence of SEQ ID NO: 129, the CDR1β consisting of the amino acid sequence of SEQ ID NO: 133, the CDR2β comprising the amino acid sequence of SEQ ID NO: 134, and the CDR3β comprising the amino acid sequence of SEQ ID NO: 135.
14. The antigen recognizing construct of claim 1, comprising the CDR1α comprising the amino acid sequence of SEQ ID NO: 127, the CDR2α consisting of the amino acid sequence of SEQ ID NO: 128, the CDR3α comprising the amino acid sequence of SEQ ID NO: 129, the CDR1β comprising the amino acid sequence of SEQ ID NO: 133, the CDR2β consisting of the amino acid sequence of SEQ ID NO: 134, and the CDR3β comprising the amino acid sequence of SEQ ID NO: 135.
15. The antigen recognizing construct of claim 1, comprising the CDR1α consisting of the amino acid sequence of SEQ ID NO: 127, the CDR2α consisting of the amino acid sequence of SEQ ID NO: 128, the CDR3α comprising the amino acid sequence of SEQ ID NO: 129, the CDR1β consisting of the amino acid sequence of SEQ ID NO: 133, the CDR2β consisting of the amino acid sequence of SEQ ID NO: 134, and the CDR3β comprising the amino acid sequence of SEQ ID NO: 135.
16. The antigen recognizing construct of claim 1, comprising the CDR1α comprising the amino acid sequence of SEQ ID NO: 127, the CDR2α consisting of the amino acid sequence of SEQ ID NO: 128, the CDR3α consisting of the amino acid sequence of SEQ ID NO: 129, the CDR1β comprising the amino acid sequence of SEQ ID NO: 133, the CDR2β consisting of the amino acid sequence of SEQ ID NO: 134, and the CDR3β consisting of the amino acid sequence of SEQ ID NO: 135.
17. The antigen recognizing construct of claim 1, comprising the CDR1α consisting of the amino acid sequence of SEQ ID NO: 127, the CDR2α consisting of the amino acid sequence of SEQ ID NO: 128, the CDR3α consisting of the amino acid sequence of SEQ ID NO: 129, the CDR1β consisting of the amino acid sequence of SEQ ID NO: 133, the CDR2β consisting of the amino acid sequence of SEQ ID NO: 134, and the CDR3β consisting of the amino acid sequence of SEQ ID NO: 135.
18. 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.
19. The antigen recognizing construct of claim 1, comprising the α variable domain comprising SEQ ID NO: 130 and the β variable domain comprising SEQ ID NO: 136.
20. The host cell of claim 8, wherein the host cell is a CD4-positive or CD8-positive T cell.
21. The pharmaceutical composition of claim 9, wherein the host cell is a CD4-positive or CD8-positive T cell.
22. The method according to claim 11, further comprising reconstitution of the antigen recognizing construct in a T-cell.
23. The antigen recognizing construct of claim 1, comprising the CDR1α comprising the amino acid sequence of SEQ ID NO: 127, the CDR2α comprising the amino acid sequence of SEQ ID NO: 128, the CDR3α consisting of the amino acid sequence of SEQ ID NO: 129, the CDR1β comprising the amino acid sequence of SEQ ID NO: 133, the CDR2β comprising the amino acid sequence of SEQ ID NO: 134, and the CDR3β consisting of the amino acid sequence of SEQ ID NO: 135.
24. A nucleic acid or two separate nucleic acids encoding the antigen recognizing construct according to claim 18.
25. A nucleic acid or two separate nucleic acids encoding the antigen recognizing construct according to claim 19.
SEQ ID NOs: 130 and 136 of the ‘145 claims comprise the claimed SEQ ID NOs: 111 and 117. See Appendix.
The ‘145 claims teach as set forth above, but do not teach treating a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface.
Alten, Heemskerk, and Ulmert teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘145 claims, Alten , Heemskerk and Ulmert and treat a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface by inducing an immune response with autologous or allogenic T cells expressing the TCRs of the ‘145 claims which recognize SLLQHLIGL because Alten teaches treating a patient who has cancer , including melanoma, with said T cells and the T-cells recognize and kill cells expressing the PRAME antigen, Heemskerk teaches that SLLQHLIGL is expressed in various cancer including metastatic melanoma and Ulmert teaches PRAME is expressed in numerous cancers like cutaneous, PRAME expression has been associated with very poor prognosis and disease progression and PRAME can be targeted for treatment. One would have been motivated to identify metastatic lesions that express SLLQHLIGL on the surface of the cells so that one would know that the metastatic cells were amenable to treatment with the with the T cells expressing the TCRs of the ‘145 claims which recognize SLLQHLIGL.
12. Claims 32 and 38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-25 of U.S. Patent No. 11,236,145 (Alten et al. Feb. 1, 2022, IDS, in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten”, in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert” as applied to claims 1-5, 12-14, 21-31, 33-37, 39 and 40 above, in further view of Toyama et al. (Modern Pathology Aug. 02, 2019 32: 1727-1733), “Toyama”.
The ‘145 claims, Alten, Heemskerk, and Ulmert teach as set forth above, but do not teach treating a mucosal melanoma.
Toyama teaches as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘145 claims, Alten, Heemskerk, Ulmert and Toyama and treat a patient who has mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘145 claims which recognize SLLQHLIGL because Toyama teaches that in mucosal melanoma the majority of melanomas expressed PRAME and PRAME is expressed in metastatic mucosal melanoma. One would have been motivated to treat mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘145 claims because Toyama teaches with the majority of mucosal melanomas in our study staining for PRAME, specifically targeting tumor cells with PRAME expression may be a strategy for therapy.
13. Claims 1-5, 12-14, 21-31, 33-37, 39 and 40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19, 21, and 36-74 of co-pending Application No. 17/553,017 (published as US 2022/0098270, IDS) in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten” and in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert”.
The ‘017 claims are drawn to:
A method of manufacturing a therapeutic population of T-cell receptor (TCR) engineered T cells comprising SEQ ID NOs: 130 and 136 and SEQ ID NOs:132 and 138
SEQ ID NOs: 130 and 136 of the ‘017 claims comprise the claimed SEQ ID NOs: 111 and 117. See Appendix.
SEQ ID NOs:132 and 138 of the ‘017 claims comprise the claimed SEQ ID NOs: 113 and 119. See Appendix.
The ‘017 claims teach as set forth above, but do not teach treating a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface.
Alten, Heemskerk, and Ulmert teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘017 claims, Alten , Heemskerk and Ulmert and treat a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface by inducing an immune response with autologous or allogenic T cells expressing the TCRs of the ‘017 claims which recognize SLLQHLIGL because Alten teaches treating a patient who has cancer , including melanoma, with said T cells and the T-cells recognize and kill cells expressing the PRAME antigen, Heemskerk teaches that SLLQHLIGL is expressed in various cancer including metastatic melanoma and Ulmert teaches PRAME is expressed in numerous cancers like cutaneous, PRAME expression has been associated with very poor prognosis and disease progression and PRAME can be targeted for treatment. One would have been motivated to identify metastatic lesions that express SLLQHLIGL on the surface of the cells so that one would know that the metastatic cells were amenable to treatment with the with the T cells expressing the TCRs of the ‘017 claims which recognize SLLQHLIGL.
This is a provisional nonstatutory double patenting rejection.
14. Claims 32 and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19, 21, and 36-74 of co-pending Application No. 17/553,017 (published as US 2022/0098270, IDS), in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten”, in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert” as applied to claims 1-5, 12-14, 21-31, 33-37, 39 and 40 above, in further view of Toyama et al. (Modern Pathology Aug. 02, 2019 32: 1727-1733), “Toyama”.
The ‘017 claims, Alten, Heemskerk, and Ulmert teach as set forth above, but do not teach treating a mucosal melanoma.
Toyama teaches as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘017 claims, Alten, Heemskerk, Ulmert and Toyama and treat a patient who has mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘017 claims which recognize SLLQHLIGL because Toyama teaches that in mucosal melanoma the majority of melanomas expressed PRAME and PRAME is expressed in metastatic mucosal melanoma. One would have been motivated to treat mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘017 claims because Toyama teaches with the majority of mucosal melanomas in our study staining for PRAME, specifically targeting tumor cells with PRAME expression may be a strategy for therapy.
This is a provisional nonstatutory double patenting rejection.
15. Claims 1-5, 12-14, 21-31, 33-37, 39 and 40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 76-93 of co-pending Application No. 18/053,705 (published as US 2023/0192886, IDS) in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten” and in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert”.
The ‘705 claims are drawn to:
A method of treating a PRAME-positive cancer, wherein said method comprises administering a therapeutically effective amount of engineered T cells to a subject in need thereof, wherein said subject is positive for HLA-A*02, and wherein said engineered T cells comprise TCRs comprising SEQ ID NOs: 111 and 117 or SEQ ID NOs: 113 and 119.
SEQ ID NOs: 111 and 117 of the ‘705 claims comprise the claimed SEQ ID NOs: 111 and 117. See Appendix.
SEQ ID NOs: 113 and 119 of the ‘705 claims comprise the claimed SEQ ID NOs: 113 and 119. See Appendix.
The ‘705 claims teach as set forth above, but do not teach treating a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface.
Alten, Heemskerk, and Ulmert teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘705 claims, Alten , Heemskerk and Ulmert and treat a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface by inducing an immune response with autologous or allogenic T cells expressing the TCRs of the ‘705 claims which recognize SLLQHLIGL because Alten teaches treating a patient who has cancer , including melanoma, with said T cells and the T-cells recognize and kill cells expressing the PRAME antigen, Heemskerk teaches that SLLQHLIGL is expressed in various cancer including metastatic melanoma and Ulmert teaches PRAME is expressed in numerous cancers like cutaneous, PRAME expression has been associated with very poor prognosis and disease progression and PRAME can be targeted for treatment. One would have been motivated to identify metastatic lesions that express SLLQHLIGL on the surface of the cells so that one would know that the metastatic cells were amenable to treatment with the with the T cells expressing the TCRs of the ‘705 claims which recognize SLLQHLIGL.
This is a provisional nonstatutory double patenting rejection.
16. Claims 32 and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 76-93 of co-pending Application No. 18/053,705 (published as US 2023/0192886, IDS) in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten”, in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert” as applied to claims 1-5, 12-14, 21-31, 33-37, 39 and 40 above, in further view of Toyama et al. (Modern Pathology Aug. 02, 2019 32: 1727-1733), “Toyama”.
The ‘705 claims, Alten, Heemskerk, and Ulmert teach as set forth above, but do not teach treating a mucosal melanoma.
Toyama teaches as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘705 claims, Alten, Heemskerk, Ulmert and Toyama and treat a patient who has mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘705 claims which recognize SLLQHLIGL because Toyama teaches that in mucosal melanoma the majority of melanomas expressed PRAME and PRAME is expressed in metastatic mucosal melanoma. One would have been motivated to treat mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘705 claims because Toyama teaches with the majority of mucosal melanomas in our study staining for PRAME, specifically targeting tumor cells with PRAME expression may be a strategy for therapy.
This is a provisional nonstatutory double patenting rejection.
17. Claims 1-31, 33-37, 39 and 40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of co-pending Application No. 19/020,283 (published as US 2025/0146019 A1) in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten” and in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert”.
The ‘283 claims are drawn to:
1. 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.
2. The nucleic acid of claim 1, wherein the TCR α chain and the TCR β chain are selected from SEQ ID NO: and 16, 17 and 18, 19 and 20, 21 and 22, 23 and 24, 25 and 26, 27 and 28, 29 and 30, 31 and 32, 33 and 34, 35 and 36, 37 and 38, 39 and 40, 41 and 42, 43 and 44, 45 and 46, 47 and 48, 49 and 50, 51 and 52, 53 and 54, 55 and 56, 57 and 58, 59 and 60, 61 and 62, 63 and 64, 65 and 66, 67 and 68, 69 and 70, 71 and 303, 304 and 74, 75 and 76, 77 and 78, 79 and 80, 81 and 82, 83 and 84, 85 and 86, 87 and 88, 89 and 90, and 91 and 92.
3. The nucleic acid of claim 1, wherein the nucleic acid sequence is at least 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the nucleic acid sequence of SEQ ID NO: 267, 269, 271, 273, 275, 277, 279, 281, 283, 285, 287, 289, 291, 295, 297, 299, or 301.
4. A polypeptide encoded by the nucleic acid of claim 1.
5. A polypeptide comprising an amino acid sequence which is at least 80%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 5, 258, 259, 262, or a variant thereof.
6. A vector comprising the nucleic acid of claim 1.
7. The vector of claim 6, wherein the vector further comprises a nucleic acid encoding a 2A peptide or an internal ribosome entry site (IRES) positioned between: (i) the nucleic acid encoding the TCR α chain and the nucleic acid encoding the TCR β chain; (ii) the nucleic acid encoding the TCR α chain and the nucleic acid encoding the CD8 polypeptide; and/or (iii) the nucleic acid encoding the TCR β chain and the nucleic acid encoding the CD8 polypeptide.
8. The vector of claim 7, wherein the 2A peptide is P2A (SEQ ID NO: 93), T2A (SEQ ID NO: 94), E2A (SEQ ID NO: 95), or F2A (SEQ ID NO: 96).
9. The vector of claim 6, wherein the vector further comprises a posttranscriptional regulatory element (PRE) sequence selected from a Woodchuck PRE (WPRE), Woodchuck PRE (WPRE) mutant 1, Woodchuck PRE (WPRE) mutant 2, and hepatitis B virus (HBV) PRE (HPRE).
10. The vector of claim 9, wherein the post-transcriptional regulatory element (PRE) sequence is (i) Woodchuck PRE (WPRE) mutant 1 comprising the amino acid sequence of SEQ ID NO: 256; or (ii) Woodchuck PRE (WPRE) mutant 2 comprising the amino acid sequence of SEQ ID NO: 257.
11. The vector of claim 6, wherein the vector further comprises a promoter selected from cytomegalovirus (CMV) promoter, phosphoglycerate kinase (PGK) promoter, myelin basic protein (MBP) promoter, glial fibrillary acidic protein (GFAP) promoter, modified MoMuLV LTR comprising myeloproliferative sarcoma virus enhancer (MNDU3), Ubiquitin C promoter, EF-1 alpha promoter, and Murine Stem Cell Virus (MSCV) promoter.
12. The vector of claim 6, wherein the vector is a viral vector or a non-viral vector.
13. The vector of claim 12, wherein the viral vector is selected from adenoviruses, poxviruses, alphaviruses, arenaviruses, flaviviruses, rhabdoviruses, retroviruses, lentiviruses, herpesviruses, paramyxoviruses, picornaviruses, and combinations thereof.
14. The vector of claim 12, wherein the viral vector is pseudotyped with an envelope protein of a virus selected from the native feline endogenous virus (RD114), a version of RD114 (RD114TR), gibbon ape leukemia virus (GaLV), a version of GaLV (GaLV-TR), amphotropic murine leukemia virus (MLV 4070A), baculovirus (GP64), vesicular stomatitis virus (VSV-G), fowl plague virus (FPV), Ebola virus (EboV), or baboon retroviral envelope glycoprotein (BaEV), and lymphocytic choriomeningitis virus (LCMV).
15. The vector of claim 6, wherein the vector is a lentiviral vector.
16. The vector of claim 6, wherein the vector further comprises a nucleic acid encoding a chimeric antigen receptor (CAR).
17. AT cell transduced with the nucleic acid of claim 1.
18. The T cell of claim 17, wherein the T cell is an αβ T cell, γδ T cell, and/or natural killer T cell.
19. The T cell of claim 18, wherein the αβ T cell is a CD4+ T cell or a CD8+ T cell.
20. The T cell of claim 18, wherein the γδ T cell is a Vγ9Vδ2+ T cell.
21. A T cell expressing the polypeptide of claim 4.
22. The T cell of claim 21, wherein said T cell is an αβ T cell, a γδ T cell, and/or a natural killer T cell.
23. A composition comprising the T cell of claim 21.
24. The composition of claim 23, wherein the composition is a pharmaceutical composition.
25. The composition of claim 23, wherein the composition further comprises an adjuvant, excipient, carrier, diluent, buffer, stabilizer, or a combination thereof.
26. 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.
27. 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.
28. A method of eliciting an immune response in 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.
The TCR α chains and the TCR β chains of the ‘283 claims (see claims 2 and 3) comprise the claimed TCR α chains and the TCR β chains. See Table 3 of US 2025/0146019.
The ‘283 claims teach as set forth above, but do not teach treating a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface.
Alten, Heemskerk, and Ulmert teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘283 claims, Alten , Heemskerk and Ulmert and treat a patient who has metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface by inducing an immune response with autologous or allogenic T cells expressing the TCRs of the ‘283 claims which recognize SLLQHLIGL because Alten teaches treating a patient who has cancer , including melanoma, with said T cells and the T-cells recognize and kill cells expressing the PRAME antigen, Heemskerk teaches that SLLQHLIGL is expressed in various cancer including metastatic melanoma and Ulmert teaches PRAME is expressed in numerous cancers like cutaneous, PRAME expression has been associated with very poor prognosis and disease progression and PRAME can be targeted for treatment. One would have been motivated to identify metastatic lesions that express SLLQHLIGL on the surface of the cells so that one would know that the metastatic cells were amenable to treatment with the with the T cells expressing the TCRs of the ‘283 claims which recognize SLLQHLIGL.
This is a provisional nonstatutory double patenting rejection.
18. Claims 32 and 38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of co-pending Application No. 19/020,283 (published as US 2025/0146019 A1)in view of US 2020/0123221 A1 (Alten et al. Apr. 23, 2020, IDS), “Alten”, in view of US 2016/0263155 A1(Heemskerk et al. Sep. 15, 2016), “Heemskerk” and in view of US 2022/0153863 A1 (Ulmert et al. May 19, 2022 filed March 13, 2020), “Ulmert” as applied to claims 1-31, 33-37, 39 and 40 above, in further view of Toyama et al. (Modern Pathology Aug. 02, 2019 32: 1727-1733), “Toyama”.
The ‘283 claims, Alten, Heemskerk, and Ulmert teach as set forth above, but do not teach treating a mucosal melanoma.
Toyama teaches as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ‘283 claims, Alten, Heemskerk, Ulmert and Toyama and treat a patient who has mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘283 claims which recognize SLLQHLIGL because Toyama teaches that in mucosal melanoma the majority of melanomas expressed PRAME and PRAME is expressed in metastatic mucosal melanoma. One would have been motivated to treat mucosal melanoma metastasis or a metastatic lesion that presents a peptide comprising SLLQHLIGL (SEQ ID NO: 310) on the cell surface with the T cells expressing the TCRs of the ‘283 claims because Toyama teaches with the majority of mucosal melanomas in our study staining for PRAME, specifically targeting tumor cells with PRAME expression may be a strategy for therapy.
This is a provisional nonstatutory double patenting rejection.
Conclusion
19. No claims allowed.
20. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Greg Emch can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PETER J REDDIG/Primary Examiner, Art Unit 1646
APPENDIX
Alignment of SEQ ID NO: 15
RESULT 7
US-16-731-139-6
; Sequence 6, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 6
; LENGTH: 273
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-6
Query Match 100.0%; Score 708; DB 20; Length 273;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRW 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRW 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKP 132
||||||||||||
Db 121 RFGAGTRLTVKP 132
Alignment of SEQ ID NO: 21
RESULT 7
US-16-731-139-12
; Sequence 12, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 12
; LENGTH: 311
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-12
Query Match 100.0%; Score 710; DB 20; Length 311;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRQTMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRQTMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVL 132
||||||||||||
Db 121 QYFGPGTRLTVL 132
Alignment of SEQ ID NO: 27
US-16-731-139-18
; Sequence 18, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 18
; LENGTH: 275
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-18
Query Match 100.0%; Score 695; DB 20; Length 275;
Best Local Similarity 100.0%;
Matches 134; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRGSQSFFWYRQY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRGSQSFFWYRQY 60
Qy 61 SGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAAVISNFGNE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAAVISNFGNE 120
Qy 121 KLTFGTGTRLTIIP 134
||||||||||||||
Db 121 KLTFGTGTRLTIIP 134
Alignment of SEQ ID NO: 33
US-16-731-139-24
; Sequence 24, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 24
; LENGTH: 311
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-24
Query Match 100.0%; Score 707; DB 20; Length 311;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MGSRLLCWVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQTPGQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MGSRLLCWVLLCLLGAGPVKAGVTQTPRYLIKTRGQQVTLSCSPISGHRSVSWYQQTPGQ 60
Qy 61 GLQFLFEYFSETQRNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASSPWDSPNE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLQFLFEYFSETQRNKGNFPGRFSGRQFSNSRSEMNVSTLELGDSALYLCASSPWDSPNE 120
Qy 121 QYFGPGTRLTVT 132
||||||||||||
Db 121 QYFGPGTRLTVT 132
Alignment of SEQ ID NO: 39
US-16-731-139-30
; Sequence 30, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 30
; LENGTH: 274
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-30
Query Match 100.0%; Score 697; DB 20; Length 274;
Best Local Similarity 100.0%;
Matches 133; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MMKSLRVLLVILWLQLSWVWSQQKEVEQDPGPLSVPEGAIVSLNCTYSNSAFQYFMWYRQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MMKSLRVLLVILWLQLSWVWSQQKEVEQDPGPLSVPEGAIVSLNCTYSNSAFQYFMWYRQ 60
Qy 61 YSRKGPELLMYTYSSGNKEDGRFTAQVDKSSKYISLFIRDSQPSDSATYLCAMSEAAGNK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YSRKGPELLMYTYSSGNKEDGRFTAQVDKSSKYISLFIRDSQPSDSATYLCAMSEAAGNK 120
Qy 121 LTFGGGTRVLVKP 133
|||||||||||||
Db 121 LTFGGGTRVLVKP 133
Alignment of SEQ ID NO: 45
US-16-731-139-36
; Sequence 36, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 36
; LENGTH: 309
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-36
Query Match 100.0%; Score 691; DB 20; Length 309;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MGTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MGTRLLCWAALCLLGAELTEAGVAQSPRYKIIEKRQSVAFWCNPISGHATLYWYQQILGQ 60
Qy 61 GPKLLIQFQNNGVVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSYTNQGE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GPKLLIQFQNNGVVDDSQLPKDRFSAERLKGVDSTLKIQPAKLEDSAVYLCASSYTNQGE 120
Qy 121 AFFGQGTRLTVV 132
||||||||||||
Db 121 AFFGQGTRLTVV 132
Alignment of SEQ ID NO: 51
US-16-731-139-42
; Sequence 42, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 42
; LENGTH: 273
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-42
Query Match 100.0%; Score 676; DB 20; Length 273;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRGSQSFFWYRQY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRGSQSFFWYRQY 60
Qy 61 SGKSPELIMSIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVLNQAGTAL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGKSPELIMSIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVLNQAGTAL 120
Qy 121 IFGKGTTLSVSS 132
||||||||||||
Db 121 IFGKGTTLSVSS 132
Alignment of SEQ ID NO: 57
US-16-731-139-48
; Sequence 48, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 48
; LENGTH: 314
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-48
Query Match 100.0%; Score 717; DB 20; Length 314;
Best Local Similarity 100.0%;
Matches 135; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MGFRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MGFRLLCCVAFCLLGAGPVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVYWYQQSLDQ 60
Qy 61 GLQFLIQYYNGEERAKGNILERFSAQQFPDLHSELNLSSLELGDSALYFCASSAETGPWL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLQFLIQYYNGEERAKGNILERFSAQQFPDLHSELNLSSLELGDSALYFCASSAETGPWL 120
Qy 121 GNEQFFGPGTRLTVL 135
|||||||||||||||
Db 121 GNEQFFGPGTRLTVL 135
Alignment of SEQ ID NO: 63
US-16-731-139-54
; Sequence 54, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 54
; LENGTH: 277
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-54
Query Match 100.0%; Score 712; DB 20; Length 277;
Best Local Similarity 100.0%;
Matches 136; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWYKQP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MACPGFLWALVISTCLEFSMAQTVTQSQPEMSVQEAETVTLSCTYDTSESDYYLFWYKQP 60
Qy 61 PSRQMILVIRQEAYKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAYRWAQGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PSRQMILVIRQEAYKQQNATENRFSVNFQKAAKSFSLKISDSQLGDAAMYFCAYRWAQGG 120
Qy 121 SEKLVFGKGTKLTVNP 136
||||||||||||||||
Db 121 SEKLVFGKGTKLTVNP 136
Alignment of SEQ ID NO: 69
US-16-731-139-60
; Sequence 60, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 60
; LENGTH: 313
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-60
Query Match 100.0%; Score 716; DB 20; Length 313;
Best Local Similarity 100.0%;
Matches 134; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MTIRLLCYMGFYFLGAGLMEADIYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQQDPGM 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MTIRLLCYMGFYFLGAGLMEADIYQTPRYLVIGTGKKITLECSQTMGHDKMYWYQQDPGM 60
Qy 61 ELHLIHYSYGVNSTEKGDLSSESTVSRIRTEHFPLTLESARPSHTSQYLCATELWSSGGT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ELHLIHYSYGVNSTEKGDLSSESTVSRIRTEHFPLTLESARPSHTSQYLCATELWSSGGT 120
Qy 121 GELFFGEGSRLTVL 134
||||||||||||||
Db 121 GELFFGEGSRLTVL 134
Alignment of SEQ ID NO: 75
US-16-731-139-66
; Sequence 66, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 66
; LENGTH: 273
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-66
Query Match 100.0%; Score 686; DB 20; Length 273;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRGSQSFFWYRQY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRGSQSFFWYRQY 60
Qy 61 SGKSPELIMSIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVGPSGTYKY 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGKSPELIMSIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVGPSGTYKY 120
Qy 121 IFGTGTRLKVLA 132
||||||||||||
Db 121 IFGTGTRLKVLA 132
Alignment of SEQ ID NO: 81
US-16-731-139-72
; Sequence 72, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 72
; LENGTH: 311
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-72
Query Match 100.0%; Score 704; DB 20; Length 311;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MGPQLLGYVVLCLLGAGPLEAQVTQNPRYLITVTGKKLTVTCSQNMNHEYMSWYRQDPGL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MGPQLLGYVVLCLLGAGPLEAQVTQNPRYLITVTGKKLTVTCSQNMNHEYMSWYRQDPGL 60
Qy 61 GLRQIYYSMNVEVTDKGDVPEGYKVSRKEKRNFPLILESPSPNQTSLYFCASSPGGSGNE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLRQIYYSMNVEVTDKGDVPEGYKVSRKEKRNFPLILESPSPNQTSLYFCASSPGGSGNE 120
Qy 121 QFFGPGTRLTVL 132
||||||||||||
Db 121 QFFGPGTRLTVL 132
Alignment of SEQ ID NO: 87
US-16-731-139-78
; Sequence 78, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 78
; LENGTH: 274
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-78
Query Match 100.0%; Score 694; DB 20; Length 274;
Best Local Similarity 100.0%;
Matches 133; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRGSQSFFWYRQY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKSLRVLLVILWLQLSWVWSQQKEVEQNSGPLSVPEGAIA SLNCTYSDRGSQSFFWYRQY 60
Qy 61 SGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVVSGGGADG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGKSPELIMFIYSNGDKEDGRFTAQLNKASQYVSLLIRDSQPSDSATYLCAVVSGGGADG 120
Qy 121 LTFGKGTHLIIQP 133
|||||||||||||
Db 121 LTFGKGTHLIIQP 133
Alignment of SEQ ID NO: 93
RESULT 7
US-16-731-139-84
; Sequence 84, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 84
; LENGTH: 319
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-84
Query Match 100.0%; Score 759; DB 20; Length 319;
Best Local Similarity 100.0%;
Matches 142; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLSPDLPDSAWNTRLLCHVMLCLLGAVSVAAGVIQSPRHLIKEKRETATLKCYPIPRHDT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLSPDLPDSAWNTRLLCHVMLCLLGAVSVAAGVIQSPRHLIKEKRETATLKCYPIPRHDT 60
Qy 61 VYWYQQGPGQDPQFLISFYEKMQSDKGSIPDRFSAQQFSDYHSELNMSSLELGDSALYFC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VYWYQQGPGQDPQFLISFYEKMQSDKGSIPDRFSAQQFSDYHSELNMSSLELGDSALYFC 120
Qy 121 ASSLGRGGQPQHFGDGTRLSIL 142
||||||||||||||||||||||
Db 121 ASSLGRGGQPQHFGDGTRLSIL 142
Alignment of SEQ ID NO: 111
US-16-731-139-132
; Sequence 132, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 132
; LENGTH: 273
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-132
Query Match 100.0%; Score 702; DB 20; Length 273;
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
US-16-731-139-138
; Sequence 138, Application US/16731139
; Publication No. US20200123221A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US03; 3000058-008003
; CURRENT APPLICATION NUMBER: US/16/731,139
; CURRENT FILING DATE: 2019-12-31
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 138
; LENGTH: 311
; TYPE: PRT
; ORGANISM: Homo sapiens
US-16-731-139-138
Query Match 100.0%; Score 710; DB 20; Length 311;
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
Alignment of SEQ ID NO: 113 with SEQ ID NO: 132 of Alten
ALIGNMENT:
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: 119 with SEQ ID NO: 138 of Alten
ALIGNMENT:
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
17/553,017 Alignments
Alignment of SEQ ID NO: 15
US-17-553-017-4
; Sequence 4, Application US/17553017
; Publication No. US20220098270A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US04; 3000058-008004; 1017-11 US
; CURRENT APPLICATION NUMBER: US/17/553,017
; CURRENT FILING DATE: 2021-12-16
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 4
; LENGTH: 132
; TYPE: PRT
; ORGANISM: Homo sapiens
US-17-553-017-4
Query Match 100.0%; Score 708; DB 22; Length 132;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRW 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRW 60
Qy 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ETAKSPEALFVMTLNGDEKKKGRISATLNTKEGYSYLYIKGSQPEDSATYLCALYNNNDM 120
Qy 121 RFGAGTRLTVKP 132
||||||||||||
Db 121 RFGAGTRLTVKP 132
Alignment of SEQ ID NO: 21
US-17-553-017-10
; Sequence 10, Application US/17553017
; Publication No. US20220098270A1
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US04; 3000058-008004; 1017-11 US
; CURRENT APPLICATION NUMBER: US/17/553,017
; CURRENT FILING DATE: 2021-12-16
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 10
; LENGTH: 132
; TYPE: PRT
; ORGANISM: Homo sapiens
US-17-553-017-10
Query Match 100.0%; Score 710; DB 22; Length 132;
Best Local Similarity 100.0%;
Matches 132; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRQTMMR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSWTFCCVSLCILVAKHTDAGVIQSPRHEVTEMGQEVTLRCKPISGHNSLFWYRQTMMR 60
Qy 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GLELLIYFNNNVPIDDSGMPEDRFSAKMPNASFSTLKIQPSEPRDSAVYFCASSPGSTDT 120
Qy 121 QYFGPGTRLTVL 132
||||||||||||
Db 121 QYFGPGTRLTVL 132
Alignment of SEQ ID NO: 111
US-17-553-017-130
; Sequence 130, Application US/17553017
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US04; 3000058-008004; 1017-11 US
; CURRENT APPLICATION NUMBER: US/17/553,017
; CURRENT FILING DATE: 2021-12-16
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 130
; LENGTH: 132
; TYPE: PRT
; ORGANISM: Homo sapiens
US-17-553-017-130
Query Match 100.0%; Score 702; DB 124; 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
US-17-553-017-136
; Sequence 136, Application US/17553017
; GENERAL INFORMATION
; APPLICANT: Immatics Biotechnologies GmbH
; TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
; TITLE OF INVENTION:POSITIVE CANCERS
; FILE REFERENCE: P172US04; 3000058-008004; 1017-11 US
; CURRENT APPLICATION NUMBER: US/17/553,017
; CURRENT FILING DATE: 2021-12-16
; PRIOR APPLICATION NUMBER: US 15/928,785
; PRIOR FILING DATE: 2018-03-22
; PRIOR APPLICATION NUMBER: US 62/475,329
; PRIOR FILING DATE: 2017-03-23
; PRIOR APPLICATION NUMBER: DE 10 2017 106 305.6
; PRIOR FILING DATE: 2017-03-23
; NUMBER OF SEQ ID NOS: 204
; SOFTWARE: PatentIn version 3.5
; SEQ ID NO 136
; LENGTH: 132
; TYPE: PRT
; ORGANISM: Homo sapiens
US-17-553-017-136
Query Match 100.0%; Score 710; DB 124; 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
Alignment of SEQ ID NO: 113 with SEQ ID NO: 6 of 10800832
US-16-403-038-6
Filing date in PALM: 2019-05-03
Sequence 6, US/16403038
Patent No. 10800832
GENERAL INFORMATION
APPLICANT: Immatics Biotechnologies GmbH
TITLE OF INVENTION: T CELL RECEPTORS AND IMMUNE THERAPY USING THE SAME AGAINST PRAME
TITLE OF INVENTION: POSITIVE CANCERS
ALIGNMENT:
Query Match 99.4%; Score 1419; Length 273;
Best Local Similarity 99.6%;
Matches 272; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRK 60
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEKNPLAAPLLILWFHLDCVSSILNVEQSPQSLHVQEGDSTNFTCSFPSSNFYALHWYRW 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: 113 with SEQ ID NO: 113 of 18/053,705
ALIGNMENT:
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: 119 with SEQ ID NO: 119 of 18/053,705
ALIGNMENT:
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