DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 06, 2026 has been entered.
2. Claims 1, 3-20, and 24-29 are pending.
3. The Declaration of Christine Brown under 37 CFR 1.130(a) filed on May 06, 2026 is sufficient to overcome the rejection of claims 1, 3-20, and 24-29 under 35 U.S.C. 103 or on the ground of nonstatutory double patenting based on US 2014/0271582 A1 (Forman et al. Sep. 18, 2014), “Forman-582”, WO 2014/144622 A3 (Forman et al. Sep. 18, 2014), “Forman-622”, or Jonnalagadda et al. (Journal for ImmunoTherapy of Cancer 2013 1(Suppl 1):P18), “Jonnalagadda” The Declaration demonstrates that Christine Brown, Stephen Forman and/or Armen Mardiros are the inventors of the disclosed subject matter of Forman-582, Forman-622, and Jonnalagadda.
4. Applicant’s arguments, amendments and the Declaration of Christine Brown have overcome the rejections and objections set forth in the Office Action of November 06, 2025, which are hereby withdrawn.
New Grounds of Rejection
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.
5. Claims 1, 3-8, 13-20, and 24-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4 and 5 of U.S. Patent No. 12,522,667 B2 (Forman et al. Jan. 13, 2026) in view of US 2012/0148552 A1 (Jensen et al. June 14, 2012, IDS), “Jensen” and in view of Jena et al. (Blood 19 Aug. 2010 116(7): 1035-1044, of record).
The ‘667 claims are drawn to:
1. A recombinant chimeric antigen receptor (CAR) comprising: an antigen recognition domain that targets a cancer associated antigen selected from the group consisting of CD19, CD20, CD123, HER2, IL-13 receptor α2, prostate stem cell antigen (PSCA), prostate-specific membrane antigen (PSMA), and tumor-associated glycoprotein-72 (TAG-72); a spacer domain comprising the amino acid sequence ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKT KPREEQFQSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEA LHNHYTQKSLSLSLGK (SEQ ID NO: 19); a transmembrane domain; a co-stimulatory intracellular signaling domain selected from the group consisting of: CD28, ICOS, OX40, CD27, DAP10, 4-1BB, p56lck, and 2B4; and a T cell receptor (TCR) zeta chain signaling domain.
2. The chimeric antigen receptor of claim 1, wherein the co-stimulatory intracellular signaling domain is 4-1BB.
4. The chimeric antigen receptor of claim 1, wherein the antigen recognition domain targets IL-13 receptor α2.
The ‘667 claims teach as set forth above, but do not teach that the CAR comprises SEQ ID NO: 3 or a variant thereof, a GM-CSFR alpha signal peptide, or that the CAR is expressed in human T cells or memory T cells from an expression vector
Jensen teaches chimeric antigen receptors (CARs) with the IL13 molecule comprising the E13Y mutation as the extracellular tumor recognition element. See abstract, ¶¶ 0009-0013 and claims 22, 28, and 29.
Jensen teaches that the CARs comprise costimulatory signaling domains that preferably are selected from CD28, 4-1BB, OX-40 or any combination of these. Preferred chimeric receptors comprise a human CD4 transmembrane region, a human IgG4 Fc and a receptor or ligand that is tumor-specific, such as an IL13 or IL3 molecule. See ¶¶ 0009-0013 and claims 22-29.
Jensen teaches that the CARs comprise the signaling domain from the zeta chain of the human CD3 complex (CD3 z). See ¶¶ 0009-0013 and claim 22.
Jensen teaches SEQ ID NO: 1 which comprises the claimed SEQ ID NO: 3 with Y at position 11. See Appendix of the Office Action of November 16, 2023.
Jensen teaches the CAR IL13-IgG4-cd28tm-CD28gg-Zeta (CO) CAR (SEQ ID NO:36). The nucleic acid SEQ ID NO: 36 encodes the claimed SEQ ID NO: 3. See Appendix of the Office Action of November 16, 2023.
Jensen teaches the E13Y mutant of IL13 increased binding to IL13Ra2 by 50 fold compared to wild-type IL-13 and specifically directs CARs to bind IL13Ra2. See ¶¶ 0044, 0047 and 0048.
Jensen teaches expressing the CARs in human T cells. See Example 1.
Jensen teaches expression vectors for expressing the CARs. See ¶¶ 0046-0047 and 0059.
Jensen teaches the DNA (SEQ ID NO:7), encoding GM-CSFR alpha signal peptide MLLLVTSLLLCELPHPAFLLIP of the claimed SEQ ID NO: 2. See Fig. 3 and SEQ ID NOs: 4 and 7.
With regard to claims 24-29, the claims limit the type or number of substitutions that can be made in SEQ ID NO: 3, if substitutions are present. However, the claims do not require substitutions to be made in SEQ ID NO: 3, which is comprised by SEQ ID NO: 1 of Jensen.
Jena teaches that CARs were developed to broaden the clinical application of T cell adoptive immunotherapy by overcoming tolerance to the desired to associated antigens. See Abstract, Introduction, and Redirect T-cell specificity through the introduction of a CAR.
Jena teaches that the advantage of using retroviral or lentiviral vectors for CAR mediated gene transfer is in the efficiency of gene transfer, which shortens the time for culturing T-cells to reach clinically significant numbers. See Gene transfer of CARS- p. 1037.
Jena teaches that central memory T cells expressing CARs demonstrated superior in vivo persistence compared to differentiated effector T cells. See p.1039-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 the ‘667 claims, Jensen, and Jena and use the IL13-E13Y (SEQ ID NO: 1) of Jensen as the IL13Ra2 recognition domain of the ‘667 claims and express the CARs of the ‘667 and Jensen in central memory T-cells with retroviral or lentiviral vectors because Jensen teaches the E13Y mutant of IL13 increased binding to IL13Ra2 by 50 fold compared to wild-type IL-13 and specifically directs CARs to bind IL13Ra2, Jensen teaches expressing the CARs in human T cells with expression vectors using a GM-CSFR alpha signal peptide and Jena teaches that CARs were developed to broaden the clinical application of T cell adoptive immunotherapy by overcoming tolerance to the desired to associated antigens, that the advantage of using retroviral or lentiviral vectors for CAR mediated gene transfer is in the efficiency of gene transfer, which shortens the time for culturing T-cells to reach clinically significant numbers, and that central memory T cells expressing CARs demonstrated superior in vivo persistence compared to differentiated effector T cells. One of skill in the art would have been motivated to use the IL13-E13Y (SEQ ID NO: 1) of Jensen in the CAR of the ‘667 claims given its enhanced binding and specificity and expand the CAR T-cells to a therapeutically effective amounts so that one could treat patients with the CAR T-cells.
6. Claims 9-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4 and 5 of U.S. Patent No. 12,522,667 B2 (Forman et al. Jan. 13, 2026) in view of US 2012/0148552 A1 (Jensen et al. June 14, 2012, IDS), “Jensen” and in view of Jena et al. (Blood 19 Aug. 2010 116(7): 1035-1044, of record) as applied to claims 1, 3-8, 13-20, and 24-29 above further in view of WO 2013/123061 A1 (Jensen, M. Aug. 22, 2013, of record), “Jensen-061” and in view of US 2007/0269446 A1 (de Sauvage et al. Nov. 22, 2007, of record), “Sauvage” evidenced by NCBI reference Sequence NP_001761 ( B-lymphocyte antigen CD19 isoform 2 precursor Nov. 4, 2012, of record), “NP_001761”.
The ‘667 claims, Jensen, and Jena teach as set forth above, but do not teach using a nucleotide sequence encoding T2A ribosomal skip of SEQ ID NO: 8 sequences linked to truncated a truncated CD19 (CD19t).
Jensen-061 teaches bispecific chimeric antigen receptors (CARs) targeting antigens, including IL-13, expressed in T cells. See abstract and Figs. 1, 2, and 6 and p. 20-lines 4-24.
Jensen-061 teaches expressing the CARs in T cells including central memory T cells. See p. 6-lines 12-22, p. 12-lines 24-26, and paragraph bridging pp. 32-33.
Jensen-061 teaches using lentiviral expression vectors to express the CARs in human T cells. See p. 3-lines 5-6 and p. 12-lines 5-10, and p. 31-lines 13-27 and p. 44-line 9 to p. 45-line 1.
Jensen-061 teaches that the CARs include the GM-CSF receptor alpha chain signal sequence (GMCSFRss) at the N-terminus. See p. 45-1st paragraph and Figs. 4 and 8-11.
The GMCSFRs comprises MLLLVTSLLLCELPHPAFLLIP which is the same as the instantly claimed SEQ ID NO: 2. See Figure 4, 9 and 11.
Jensen-061 teaches that the nucleic acids encoding the CARs include T2A ribosomal skip sequences linked to truncated to EGFR (EGFRt) or truncated CD19 (CD19t) as markers of CAR expression. See p. 2-2nd paragraph, Examples 1-4, 8 and 9 and Figs. 2-6, and 10-13.
The T2A sequence comprises LEGGGEGRGSLLTCGDVEENPGPR, which is the same as SEQ ID NO: 8. See Figure 4, amino acid residues 710-733.
Sauvage teaches isolation of Tumor Antigens of Hematopoietic Origin polypeptides ("TAHO" polypeptides) which are expected to serve as effective targets for cancer therapy in mammals. See abstract and ¶ [0010].
Sauvage teaches isolation of TAHO25/CD19/SEQ ID NO: 4.
TAHO25/CD19/SEQ ID NO: 4 comprises the currently claimed SEQ ID NO: 9. See Appendix of the Office Action of April 03, 2023.
TAHO25/CD19/SEQ ID NO: 4 is 467 amino acids, which is a truncation of full length 556 amino acid CD19. See Appendix of the Office Action of April 03, 2023 and NP_001761
Sauvage teaches generating antibodies to TAHO25/CD19/SEQ ID NO: 4 for detection of the TAHO25/CD19/SEQ ID NO: 4 on the cell surface. See Examples 9, 13, and 14.
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 ‘667 claims, Jensen, Jena, Jensen-061 and Sauvage and express the CARs of Jensen with EGFRt or CD19t linked to a T2A sequence as taught by Jensen-061 to mark and detect cells that are expressing the CARs as taught by Jensen-061 because Sauvage teaches generating antibodies to TAHO25/CD19/SEQ ID NO: 4 and detecting it on cell surfaces. Given the efficacy of the detection reagents for AHO25/CD19/SEQ ID NO: 4 of Sauvage, one would have been motivated to use TAHO25/CD19/SEQ ID NO: 4 for detection of cells that are expressing the CARs of the ‘667 claims, Jensen, and Jena.
7. Claims 24-29 are alternatively rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4 and 5 of U.S. Patent No. 12,522,667 B2 (Forman et al. Jan. 13, 2026) in view of US 2012/0148552 A1 (Jensen et al. June 14, 2012, IDS), “Jensen” and in view of Jena et al. (Blood 19 Aug. 2010 116(7): 1035-1044, of record) as applied to claims 1, 3-8, 13-20, and 24-29 above further in view of WO 01/34645 A2 (Puri et al. May 17, 2001, of record), “Puri”.
The ‘667 claims, Jensen, and Jena teach as set forth above, but do not teach conservative substitutions or single amino acid substitutions of the IL13 molecule compared to the claimed SEQ ID NO: 3.
Puri teaches mutated IL-13 agonist molecules in which one or more of the residues at positions 112, 110, 109, 92, 69, or 66 are mutated to a neutrally charged residue, or one with a charge opposite to the charge of the residue found at that position in native IL-13. See abstract and paragraphs bridging pp. 7-8 and pp. 8-9.
Puri teaches that the mutated IL-13 molecules have affinity for the IL-13 receptor at least about 3 times greater than that exhibited by wild-type IL-13. See abstract paragraph bridging pp. pp. 8-9 and Examples 17-19.
Puri teaches the mutated IL-13 molecules may contains conservative substitutions at positions not expected to be part of binding to the IL-13 receptor. See paragraph bridging pp. 20-21 and p. 31-line 22 to p. 32-line 35.
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 ‘667 claims, Jensen, and Jena, and Puri and make one or more the mutations of IL13 of Puri in the IL13 molecule of the CAR the ‘667 claims, Jensen, and Jena because Puri teaches the mutations increase the affinity of IL-13 molecule for the IL13 receptor. One would have been motivated to make the make one or more the mutations of IL13 of Puri in the IL13 molecule of the CAR Jensen to increase the specificity and efficacy of the CAR of the ‘667 claims, Jensen, and Jena.
8. Claims 1, 3-5, 13, 17-20, and 27-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6-10 and 24 of U.S. Patent No. 12,551,557 B2 (Brown et al. Feb. 17, 2026).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘557 claims are drawn to:
1. A nucleic acid molecule comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the chimeric antigen receptor comprises: targeting domain comprising an amino acid sequence selected from: SEQ ID NO: 30-37; a spacer domain; a transmembrane domain; a costimulatory domain and a CD3zeta domain.
2. The nucleic acid molecule of claim 1, wherein the spacer domain is selected from the group consisting of: and IgG4(EQ) spacer domain, a IgG4(HL-CH3) spacer domain and an IgG4(CH3) spacer domain.
4. The nucleic acid molecule of claim 1, wherein the transmembrane domain is selected from the group consisting of: a CD4 transmembrane domain, a CD8 transmembrane domain, and a CD28 transmembrane domain, and wherein the co-stimulatory domain is selected from a CD28 costimulatory domain, and CD28gg costimulatory domain, and a 41-BB co-stimulatory domain.
6. The nucleic acid molecule of claim 1, wherein the CAR comprises or consists of an amino acid sequence selected from the group consisting of: SEQ ID NO: 39-68 wherein the spacer having the amino acid sequence of SEQ ID NO: 10 is replaced by the amino acid sequence of any of SEQ ID NOs: 2-9 and 11.
7. A nucleic acid molecule comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the chimeric antigen receptor comprises: a targeting domain comprising an amino acid sequence comprising a variant IL13 domain comprising 109, 110, 111, contiguous amino acids of SEQ ID NO: 1 or the entirety of SEQ ID NO: 1 with 1, 2, 3, 4 or 5 single amino acid changes, provided that there is an amino acid other than E at position 90 of SEQ ID NO:1; a spacer domain; a transmembrane domain; a costimulatory domain; and a CD3zeta domain.
8. The nucleic acid molecule of claim 7, wherein there is an L at position 90 of SEQ ID NO: 1.
9. The nucleic acid molecule of claim 1, wherein the spacer domain comprises the amino acid sequence of any of SEQ ID NOs: 2-12, and wherein the costimulatory domain comprises the amino acid sequence of any of SEQ ID NOs: 22-25.
10. The nucleic molecule of claim 1, wherein the CAR comprises the amino acid sequence of any of SEQ ID NOs: 39-68 with up to 5 single amino acid substitutions.
11. A vector or an expression vector comprising the nucleic acid molecule of claim 1.
12. A population of human T cells or NK cells harboring the nucleic acid molecule of claim 1.
13. The population of human T cells of claim 12, wherein the population of human T cells comprise central memory T cells, naive memory T cells, pan T cells, or PBMC substantially depleted for CD25+ cells and CD14+ cells.
14. A method of treating a patient suffering from glioblastoma, pancreatic ductal adenocarcinoma, melanoma, ovarian carcinoma, renal cell carcinoma, breast cancer or lung cancer, comprising administering to the patient a population of autologous or allogeneic human T cells or NK cells harboring the nucleic acid molecule of claim 1.
15. The method of claim 14, wherein the cells are administered locally or systemically.
16. The method of claim 14, wherein the cells are administered intraventricularly.
17. The method of claim 14, wherein the human T cells or NK cells administered by single or repeat dosing.
18. A method of preparing CAR T cells or CAR NK cells comprising: providing a population of autologous or allogeneic human T cells or NK cells and transducing the cells with a vector comprising the nucleic acid molecule of claim 1.
19. A polypeptide encoded by the nucleic acid molecule of claim 1.
20. The nucleic acid molecule of claim 1, wherein the nucleic acid molecule is RNA or DNA.
24. The nucleic acid molecule of claim 1, wherein the targeting domain comprises or consists of the amino acid of SEQ ID NO: 33.
SEQ ID NO: 11 of the ‘557 claims comprises the claimed SEQ ID NO: 4. See Table 1 and Appendix.
SEQ ID NO: 33 of the ‘557 claims comprises SEQ ID NO: 3 with an L at position 90. See column 70-lines 25-35 and Appendix.
Thus the instant claims are not patentably distinct from the patented claims because they relate to the same inventive concept and would have been obvious in view of the patented claims which have all of the characteristics of the claimed population of human T cells expressing a chimeric antigen receptor, wherein chimeric antigen receptor comprises: a human IL-13 variant comprising the amino acid sequence of SEQ ID NO: 3 with up to 5 single amino acid substitutions, provided that the amino acid at position 11 of SEQ ID NO: 3 is an amino acid other than E; a spacer domain comprising SEQ ID NO: 4;a transmembrane domain selected from: a CD4 transmembrane domain, a CD8 transmembrane domain, and a CD28 transmembrane domain; a single costimulatory domain which is a 41BB co-stimulatory domain; and CD3z signaling domain.
9. Claims 6-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 6-10 and 24 of U.S. Patent No. 12,551,557 B2 (Brown et al. Feb. 17, 2026) as applied to claims 1, 3-5, 13, 17-20, and 27-29 above further in view of WO 2013/123061 A1 (Jensen, M. Aug. 22, 2013, of record), “Jensen-061” and in view of US 2007/0269446 A1 (de Sauvage et al. Nov. 22, 2007, of record), “Sauvage” evidenced by NCBI reference Sequence NP_001761 ( B-lymphocyte antigen CD19 isoform 2 precursor Nov. 4, 2012, of record), “NP_001761”.
The ‘557 claims teach as set forth above, but do not teach using a lentiviral vector, a GM-CSFRa signal sequence, or a nucleotide sequence encoding T2A ribosomal skip of SEQ ID NO: 8 sequences linked to truncated a truncated CD19 (CD19t).
Jensen-061 and Sauvage 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 ‘557 claims, Jensen-061 and Sauvage and express the CARs of the ‘557 claims with a GMCSFR signal sequence using a lentiviral vector as taught by Jensen-061 to facilitate expression in human T cells and with EGFRt or CD19t linked to a T2A sequence as taught by Jensen-061 to mark and detect cells that are expressing the CARs as taught by Jensen-061 because Sauvage teaches generating antibodies to TAHO25/CD19/SEQ ID NO: 4 and detecting it on cell surfaces. Given the efficacy of the detection reagents for AHO25/CD19/SEQ ID NO: 4 of Sauvage, one would have been motivated ‘557 claims and Jensen-061.
10. Claims 1, 4, 5, 7-12, 14-19 and 24-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. US Pat. No. 12,472,233 B2 (Badie Nov. 18, 2025).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘233 claims are drawn to .
1. A method of treating a glioma in a human patient comprising administering intraventricularly to the patient a composition comprising an effective amount of T cells expressing a chimeric antigen receptor that binds to IL13 receptor α2.
2. The method of claim 1 wherein the T cells are autologous or allogenic T cells.
14. The method of claim 1, wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 3.
15. The method of claim 1, wherein the chimeric antigen receptor comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 31-48.
16. The method of claim 1, wherein the chimeric antigen receptor comprises amino acids 23-540 of SEQ ID NO: 10.
The autologous T cells would be human T cells from the human patient.
The claimed SEQ ID NO: 10 comprises the IL-13 of SEQ ID NO: 3. See Fig. 9A-9B and Appendix.
The claimed SEQ ID NO: 10 comprises SEQ ID NO: 4. See Fig. 9A-9B and Appendix
The claimed SEQ ID NO: 10 comprises the GM-CSFR alpha signal peptide MLLLVTSLLLCELPHPAFLLIP of SEQ ID NO: 2. See Fig. 9A-9B.
The claimed SEQ ID NO: 10 comprises the T2A ribosome skip sequence LEGGGEGRGSLLTCGDVEENPGPR of SEQ ID NO:8. See Fig. 9A-9B.
The claimed SEQ ID NO: 10 comprises the truncated CD19 of SEQ ID NO: 9 See Fig. 9A-9B and Appendix.
The claimed SEQ ID NO: 10 comprises a CD4 transmembrane domain, a 4-1BB co-stimulatory domain and CD3 zeta signaling domain. . See Fig. 9A-9B.
With regard to claims 24-29, the claims limit the type or number of substitutions that can be made in SEQ ID NO: 3, if substitutions are present. However, the claims do not require substitutions to be made in SEQ ID NO: 3, which is comprised by the claimed SEQ ID NO: 10.
SEQ ID NOs: 34 of the ‘233 claims comprises IL13(EmY)-IgG4 (L235E,N297Q)-CD8tm-41BB-Zeta with a GMCSFRa signal peptide and is identical to the SEQ ID NO: 34 of the instant specification. See Fig. 14 and Appendix.
One of skill in the would have immediately understood that to express the chimeric antigen receptor that binds to IL13 receptor α2 in the human T cell population nucleic acid expression vectors expressing the CAR would need to be introduced into the T cells. Thus the instant claims are not patentably distinct from the patented claims because they relate to the same inventive concept and would have been obvious in view of the patented claims which have all of the characteristics of the claimed population of human T cells expressing a chimeric antigen receptor, wherein chimeric antigen receptor comprises: a human IL-13 variant comprising the amino acid sequence of SEQ ID NO: 3 with up to 5 single amino acid substitutions, provided that the amino acid at position 11 of SEQ ID NO: 3 is an amino acid other than E; a spacer domain comprising SEQ ID NO: 4;a transmembrane domain selected from: a CD4 transmembrane domain or a CD8 transmembrane domain; a single costimulatory domain which is a 41BB co-stimulatory domain; and CD3z signaling domain.
11. Claims 3, 6, 13 and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. US Pat. No. 12,472,233 B2 (Badie Nov. 18, 2025) as applied to claims 1, 4, 5, 7-12, 14-19 and 24-29 above in further view of Jena et al. (Blood 19 Aug. 2010 116(7): 1035-1044, of record).
The ‘233 claims teach as set forth above, but do not teach using central memory T cells or lentiviral vectors.
Jena 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 ‘233 claims and Jena express the CARs of the ‘233 claims in central memory T-cells with retroviral or lentiviral vectors because Jena teaches that CARs were developed to broaden the clinical application of T cell adoptive immunotherapy by overcoming tolerance to the desired to associated antigens, that the advantage of using retroviral or lentiviral vectors for CAR mediated gene transfer is in the efficiency of gene transfer, which shortens the time for culturing T-cells to reach clinically significant numbers, and that central memory T cells expressing CARs demonstrated superior in vivo persistence compared to differentiated effector T cells. One of skill in the art would have been motivated to expand the CAR memory T-cells to a therapeutically effective amounts so that one could treat patients with the CAR memory T-cells.
12. Claims 24-29 are alternatively rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. US Pat. No. 12,472,233 B2 (Badie Nov. 18, 2025)) as applied to claims 1, 4, 5, 7-12, 14-19 and 24-29 above further in view of WO 01/34645 A2 (Puri et al. May 17, 2001, of record), “Puri”.
The ‘233 claims teach as set forth above, but do not teach conservative substitutions or single amino acid substitutions of the IL13 molecule compared to the claimed SEQ ID NO: 3.
Puri 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 ‘233 claims and Puri and make one or more the mutations of IL13 of Puri in the IL13 molecule of the CAR the ‘233 claims because Puri teaches the mutations increase the affinity of IL-13 molecule for the IL13 receptor. One would have been motivated to make the make one or more the mutations of IL13 of Puri in the IL13 molecule of the CAR Jensen to increase the specificity and efficacy of the CAR of the‘233 claims.
13. Claims 1, 4, 5, 7-12, 14-19 and 24-29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 8-10, 17, 18, 20-23, 27-29, 53, 79, 94, and 125-127 of co-pending Application No. 19/351,506 (reference application published as US 2026/0027181 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘506 claims are drawn to .
1. A method of treating a human patient with a malignancy of the central nervous system comprising administering intraventricularly to the patient a composition comprising an effective amount of T cells expressing a chimeric antigen receptor.
2. The method of claims 1 wherein the T cells are autologous or allogenic T cells.
125. The method of claim 1, wherein the chimeric antigen receptor comprises the amino acid sequence of SEQ ID NO: 3.
126. The method of claim 1, wherein the chimeric antigen receptor comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 31-48.
127. The method of claim 1, wherein the chimeric antigen receptor comprises amino acids 23-540 of SEQ ID NO: 10.
The autologous T cells would be human T cells from the human patient.
The claimed SEQ ID NO: 10 comprises the IL-13 of SEQ ID NO: 3. See Fig. 9A-9B and Appendix.
The claimed SEQ ID NO: 10 comprises SEQ ID NO: 4. See Fig. 9A-9B and Appendix
The claimed SEQ ID NO: 10 comprises the GM-CSFR alpha signal peptide MLLLVTSLLLCELPHPAFLLIP of SEQ ID NO: 2. See Fig. 9A-9B.
The claimed SEQ ID NO: 10 comprises the T2A ribosome skip sequence LEGGGEGRGSLLTCGDVEENPGPR of SEQ ID NO:8. See Fig. 9A-9B.
The claimed SEQ ID NO: 10 comprises the truncated CD19 of SEQ ID NO: 9 See Fig. 9A-9B and Appendix.
The claimed SEQ ID NO: 10 comprises a CD4 transmembrane domain, a 4-1BB co-stimulatory domain and CD3 zeta signaling domain. . See Fig. 9A-9B.
With regard to claims 24-29, the claims limit the type or number of substitutions that can be made in SEQ ID NO: 3, if substitutions are present. However, the claims do not require substitutions to be made in SEQ ID NO: 3, which is comprised by the claimed SEQ ID NO: 10.
SEQ ID NOs: 34 of the ‘233 claims comprises IL13(EmY)-IgG4 (L235E,N297Q)-CD8tm-41BB-Zeta with a GMCSFRa signal peptide and is identical to the SEQ ID NO: 34 of the instant specification. See Fig. 14 and Appendix.
One of skill in the would have immediately understood that to express the chimeric antigen receptor that binds to IL13 receptor α2 in the human T cell population nucleic acid expression vectors expressing the CAR would need to be introduced into the T cells. Thus the instant claims are not patentably distinct from the co-pending claims because they relate to the same inventive concept and would have been obvious in view of the co-pending claims which have all of the characteristics of the claimed population of human T cells expressing a chimeric antigen receptor, wherein chimeric antigen receptor comprises: a human IL-13 variant comprising the amino acid sequence of SEQ ID NO: 3 with up to 5 single amino acid substitutions, provided that the amino acid at position 11 of SEQ ID NO: 3 is an amino acid other than E; a spacer domain comprising SEQ ID NO: 4;a transmembrane domain selected from: a CD4 transmembrane domain or a CD8 transmembrane domain; a single costimulatory domain which is a 41BB co-stimulatory domain; and CD3z signaling domain.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
14. Claims 3, 6, 13 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 8-10, 17, 18, 20-23, 27-29, 53, 79, 94, and 125-127 of co-pending Application No. 19/351,506 (reference application published as US 2026/0027181 A1) as applied to claims 1, 4, 5, 7-12, 14-19 and 24-29 above in further view of Jena et al. (Blood 19 Aug. 2010 116(7): 1035-1044, of record).
The ‘506 claims teach as set forth above, but do not teach using central memory T cells or lentiviral vectors.
Jena 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 ‘506 claims and Jena express the CARs of the ‘506 claims in central memory T-cells with retroviral or lentiviral vectors because Jena teaches that CARs were developed to broaden the clinical application of T cell adoptive immunotherapy by overcoming tolerance to the desired to associated antigens, that the advantage of using retroviral or lentiviral vectors for CAR mediated gene transfer is in the efficiency of gene transfer, which shortens the time for culturing T-cells to reach clinically significant numbers, and that central memory T cells expressing CARs demonstrated superior in vivo persistence compared to differentiated effector T cells. One of skill in the art would have been motivated to expand the CAR memory T-cells to a therapeutically effective amounts so that one could treat patients with the CAR memory T-cells.
This is a provisional nonstatutory double patenting rejection.
15. Claims 24-29 are alternatively provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 8-10, 17, 18, 20-23, 27-29, 53, 79, 94, and 125-127 of co-pending Application No. 19/351,506 (reference application published as US 2026/0027181 A1) as applied to claims 1, 4, 5, 7-12, 14-19 and 24-29 above further in view of WO 01/34645 A2 (Puri et al. May 17, 2001, of record), “Puri”.
The ‘506 claims teach as set forth above, but do not teach conservative substitutions or single amino acid substitutions of the IL13 molecule compared to the claimed SEQ ID NO: 3.
Puri 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 ‘506 claims and Puri and make one or more the mutations of IL13 of Puri in the IL13 molecule of the CAR the ‘506 claims because Puri teaches the mutations increase the affinity of IL-13 molecule for the IL13 receptor. One would have been motivated to make the make one or more the mutations of IL13 of Puri in the IL13 molecule of the CAR Jensen to increase the specificity and efficacy of the CAR of the ‘506 claims.
This is a provisional nonstatutory double patenting rejection.
Conclusion
16. No claims allowed.
17. 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: 4 with SEQ ID NO: 11 of US 12,551,557
Title: US-16-867-803E-4
Perfect score: 1239
Sequence: 1 ESKYGPPCPPCPAPEFEGGP..........MHEALHNHYTQKSLSLSLGK 229
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 229 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 50 summaries
Database : 17-910931.fasta:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 1239 100.0 229 1 17-910931 SEQ ID 11
ALIGNMENTS
RESULT 1
17-910931
Query Match 100.0%; Score 1239; DB 1; Length 229;
Best Local Similarity 100.0%;
Matches 229; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWY 60
Qy 61 VDGVEVHNAKTKPREEQFQSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VDGVEVHNAKTKPREEQFQSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK 120
Qy 121 AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL 180
Qy 181 DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 229
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 229
Alignment of SEQ ID NO: 3 with SEQ ID NO: 33 of US 12,551,557
Title: US-16-867-803E-3
Perfect score: 579
Sequence: 1 GPVPPSTALRYLIEELVNIT..........QFVKDLLLHLKKLFREGRFN 112
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 112 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 50 summaries
Database : 17910931-SEQ.fasta:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 571 98.6 112 1 17910931-SEQ 33
ALIGNMENTS
RESULT 1
17910931-SEQ
Query Match 98.6%; Score 571; DB 1; Length 112;
Best Local Similarity 99.1%;
Matches 111; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 GPVPPSTALRYLIEELVNITQNQKAPLCNGSMVWSINLTAGMYCAALESLINVSGCSAIE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GPVPPSTALRYLIEELVNITQNQKAPLCNGSMVWSINLTAGMYCAALESLINVSGCSAIE 60
Qy 61 KTQRMLSGFCPHKVSAGQFSSLHVRDTKIEVAQFVKDLLLHLKKLFREGRFN 112
||||||||||||||||||||||||||||| ||||||||||||||||||||||
Db 61 KTQRMLSGFCPHKVSAGQFSSLHVRDTKILVAQFVKDLLLHLKKLFREGRFN 112
Alignment of SEQ ID NO: 3 with SEQ ID NO: 10 of US 12,472,233
Title: US-16-867-803E-3
Perfect score: 579
Sequence: 1 GPVPPSTALRYLIEELVNIT..........QFVKDLLLHLKKLFREGRFN 112
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 889 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 50 summaries
Database : US12742233.fasta:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 579 100.0 889 1 US12742233 SEQ 10
ALIGNMENTS
RESULT 1
US12742233
Query Match 100.0%; Score 579; DB 1; Length 889;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GPVPPSTALRYLIEELVNITQNQKAPLCNGSMVWSINLTAGMYCAALESLINVSGCSAIE 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 23 GPVPPSTALRYLIEELVNITQNQKAPLCNGSMVWSINLTAGMYCAALESLINVSGCSAIE 82
Qy 61 KTQRMLSGFCPHKVSAGQFSSLHVRDTKIEVAQFVKDLLLHLKKLFREGRFN 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 83 KTQRMLSGFCPHKVSAGQFSSLHVRDTKIEVAQFVKDLLLHLKKLFREGRFN 134
Alignment of SEQ ID NO: 4 with SEQ ID NO: 10 of US 12,472,233
Title: US-16-867-803E-4
Perfect score: 1239
Sequence: 1 ESKYGPPCPPCPAPEFEGGP..........MHEALHNHYTQKSLSLSLGK 229
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 889 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 50 summaries
Database : AASEQ2_06042026_133836.fasta:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 1239 100.0 889 1 AASEQ2_06042026_133836
ALIGNMENTS
RESULT 1
AASEQ2_06042026_133836
Query Match 100.0%; Score 1239; DB 1; Length 889;
Best Local Similarity 100.0%;
Matches 229; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 135 ESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWY 194
Qy 61 VDGVEVHNAKTKPREEQFQSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 195 VDGVEVHNAKTKPREEQFQSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISK 254
Qy 121 AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 255 AKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL 314
Qy 181 DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 229
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 315 DSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 363
Alignment of SEQ ID NO: 9 with SEQ ID NO: 10 of US 12,472,233
Title: US-16-867-803E-9
Perfect score: 1760
Sequence: 1 MPPPRLLFFLLFLTPMEVRP..........LCSLVGILHLQRALVLRRKR 323
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 889 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 50 summaries
Database : SEQ.fasta:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 1760 100.0 889 1 SEQ ID NO: 10
ALIGNMENTS
RESULT 1
SEQ
Query Match 100.0%; Score 1760; DB 1; Length 889;
Best Local Similarity 100.0%;
Matches 323; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MPPPRLLFFLLFLTPMEVRPEEPLVVKVEEGDNAVLQCLKGTSDGPTQQLTWSRESPLKP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 567 MPPPRLLFFLLFLTPMEVRPEEPLVVKVEEGDNAVLQCLKGTSDGPTQQLTWSRESPLKP 626
Qy 61 FLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGE 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 627 FLKLSLGLPGLGIHMRPLAIWLFIFNVSQQMGGFYLCQPGPPSEKAWQPGWTVNVEGSGE 686
Qy 121 LFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPEIWEGEPPCVPPRDSL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 687 LFRWNVSDLGGLGCGLKNRSSEGPSSPSGKLMSPKLYVWAKDRPEIWEGEPPCVPPRDSL 746
Qy 181 NQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMW 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 747 NQSLSQDLTMAPGSTLWLSCGVPPDSVSRGPLSWTHVHPKGPKSLLSLELKDDRPARDMW 806
Qy 241 VMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITARPVLWHWLLRTGGWKVSAVTLAYL 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 807 VMETGLLLPRATAQDAGKYYCHRGNLTMSFHLEITARPVLWHWLLRTGGWKVSAVTLAYL 866
Qy 301 IFCLCSLVGILHLQRALVLRRKR 323
|||||||||||||||||||||||
Db 867 IFCLCSLVGILHLQRALVLRRKR 889
Alignment of SEQ ID NO: 34 with SEQ ID NO: 34 of US 12,472,233
ALIGNMENT:
Query Match 100.0%; Score 2880; Length 541;
Best Local Similarity 100.0%;
Matches 541; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MLLLVTSLLLCELPHPAFLLIPGPVPPSTALRYLIEELVNITQNQKAPLCNGSMVWSINL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MLLLVTSLLLCELPHPAFLLIPGPVPPSTALRYLIEELVNITQNQKAPLCNGSMVWSINL 60
Qy 61 TAGMYCAALESLINVSGCSAIEKTQRMLSGFCPHKVSAGQFSSLHVRDTKIEVAQFVKDL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TAGMYCAALESLINVSGCSAIEKTQRMLSGFCPHKVSAGQFSSLHVRDTKIEVAQFVKDL 120
Qy 121 LLHLKKLFREGRFNESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LLHLKKLFREGRFNESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVV 180
Qy 181 DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFQSTYRVVSVLTVLHQDWLNGKEYKCKVS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFQSTYRVVSVLTVLHQDWLNGKEYKCKVS 240
Qy 241 NKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 NKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESN 300
Qy 301 GQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLS 360
Qy 361 LGKIYIWAPLAGTCGVLLLSLVITKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEE 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LGKIYIWAPLAGTCGVLLLSLVITKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEE 420
Qy 421 EGGCELGGGRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRR 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 EGGCELGGGRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRR 480
Qy 481 KNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPP 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 KNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPP 540
Qy 541 R 541
|
Db 541 R 541
Prosecution Insights