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 .
Status of the Claims
Claims 1, 5 – 8, and 24 – 26 were pending. Claims 1, 5 – 8, and 24 – 26 were amended, and claims 27 – 54 were newly added. Claims 1, 5 – 8, and 24 – 54 are currently pending and are the subject of this Office Action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application Nos. 62/828,770, 62/795,810 01/23/2019, 62/774,595, 62/769,987 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. In particular, the listed provisional applications fail to support SEQ ID NO: 524 or present claim 25; SEQ ID NOs: 535 of present claim 26; SEQ ID NOs: 332, 341, and 469 of present claim 29; SEQ ID NO: 457 of present claim 31; SEQ ID NO: 287 of present claim 47; SEQ ID NO: 328 of present claim 48; and SEQ ID NO: 310 of present claim 49. However those sequences do seem to have support from provisional application 62/846,563, filed 05/10/2019, and thus, the effective filing date of the present claims 25 – 26, 29, and 31, 47 – 49 is 5/10/2019.
WITHDRAWN REJECTIONS
Claim Rejections - 35 USC § 103
Claims 1, 5, and 26 were rejected under 35 U.S.C. 103 as being unpatentable over XIAO (WO 2017/167217 A1, published 10/05/2017; see PTO-892: Notice of References Cited of 01/15/2025) in view of KONERU (Koneru, M. et al. A Phase I Clinical Trial of Adoptive T Cell Therapy Using IL-12 Secreting MUC-16(Ecto) Directed Chimeric Antigen Receptors for Recurrent Ovarian Cancer. Journal of translational medicine 13 (2015)), OLADAPO (Oladapo, O. et al. Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy. Biochem Soc Trans 15 April 2016; 44 (2): 412–418; See PTO-892 of 06/25/2024), and CRANE (WO 2017/ A1, published 03/16/2017; see PTO-892 of 06/25/2024).
In view of the claim amendments of 12/10/2025, this rejection is withdrawn.
Claims 6 – 8 were rejected under 35 U.S.C. 103 as being unpatentable over XIAO in view of KONERU, OLADAPO, and CRANE as applied to claims 1, 5, 26 above and further in view of LU (Lu, Ming-Yu et al. Generation of Murine Induced Pluripotent Stem Cells by Using High-Density Distributed Electrodes Network. Biomicrofluidics 9.5 (2015): 054107–054107; see PTO-892 of 06/25/2024).
In view of the claim amendments of 12/10/2025, this rejection is withdrawn.
claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over XIAO in view of KONERU, OLADAPO, AND CRANE as applied to claims 1, 5, 26 above and further in view of JUNE (WO 2012/079000 A1, published 6/14/2012)(See PTO-892 of 01/15/2025).
Claim 25 was rejected under 35 U.S.C. 103 as being unpatentable over XIAO in view of KONERU, OLADAPO, and CRANE as applied to claims 1, 5, 26 above, and further in view of XIAO 2 (US 2019/0216851 A1, filed 09/28/2018; see PTO-892).
In view of the claim amendments of 12/10/2025, this rejection is withdrawn.
Double Patenting
Claims 1, 5 – 8, and 24 – 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 7 – 10, and 18 – 20 of U.S. Patent No. 11,944,645 in view of XIAO, KONERU, OLADAPO, LU, JUNE, and XIAO 2.
In view of the claim amendments of 12/10/2025, this rejection is withdrawn.
Claims 1, 5 – 8, and 24 – 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4 – 6, 8 – 13, 15 – 18 of U.S. Patent No. 11,788,072 in view of XIAO, KONERU, OLADAPO, LU, JUNE, and XIAO 2.
In view of the claim amendments of 12/10/2025, this rejection is withdrawn.
Claims 1, 5 – 8, and 24 – 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, 7 – 9, 15, 16, 18, 21, and 22 of U.S. Patent No. 11,104,732 in view of XIAO, KONERU, OLADAPO, LU, JUNE, and XIAO 2.
In view of the claim amendments of 12/10/2025, this rejection is withdrawn.
Claims 1, 5 – 8, and 24 – 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5 – 10 of U.S. Patent No. 11,739,136 in view of XIAO, KONERU, OLADAPO, LU, JUNE, and XIAO 2.
Claims 1, 5 – 8, and 24 – 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims 1, 5 – 8, 18, and 19 of copending Application No. 18/043,021 in view of XIAO, KONERU, OLADAPO, LU, JUNE, and XIAO 2.
Claims 1, 5 – 8, and 24 – 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims 1, 9 – 16, and 19 of copending Application No. 18/156,482 in view of XIAO, KONERU, OLADAPO, LU, JUNE, and XIAO 2.
Claims 1, 5 – 8, and 24 – 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims 1, 3, 5, 7 – 10, 12, and 15 of copending Application No. 17/996,589 in view of XIAO, KONERU, OLADAPO, LU, JUNE, and XIAO 2.
NEW OBJECTIONS AND REJECTIONS
Claim Objections
Claim 25 is objected to because of the following informalities: a conjunction seems to be missing between “SEQ ID NO: 11” and “SEQ ID NO: 534”. Appropriate correction is required. For the purpose of compact prosecution, “or” is assumed to be the conjunction.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
1. Claims 1, 6 – 8, 28, 32 – 35, 40 – 41, 50 and 53 – 54 are rejected under 35 U.S.C. 103 as being unpatentable over DRANOFF (WO 201/7149515 A1, published 09/08/2017; see PTO-892: Notice of References Cited submitted with this Office Action) in view of OLADAPO (Oladapo, O. et al. Armored CAR T-cells: utilizing cytokines and pro-inflammatory ligands to enhance CAR T-cell anti-tumour efficacy. Biochem Soc Trans 15 April 2016; 44 (2): 412–418; See PTO-892 of 06/25/2024), and CARSGEN (WO 2017/186121 A1, published 11/02/2017; see PTO-892).
The present application is directed to a composition for transfecting or transducing T cells, comprising: a first vector comprising a polynucleotide encoding a first chimeric antigen receptor (CAR) binding a solid tumor antigen selected from the group consisting of TSHR, GUCY2C, and ACPP, a second vector comprising a polynucleotide encoding a second CAR binding CD19 and a polynucleotide encoding IL-6;a third vector comprising a polynucleotide encoding the second CAR and a polynucleotide encoding IL-12; and a fourth vector comprising a polynucleotide encoding the second CAR and a polynucleotide encoding IFNγ, and wherein the expression and/or secretion of each of IL-6, IL-12, and IFNγ is regulated by one or more transcription modulators, optionally wherein the one or more transcription modulators are selected from the group consisting of Hif-1α, NFAT, FOXP3, and NFkB.
DRANOFF is directed to compositions and methods for treating diseases associated with expression of a tumor antigen by the administration of a cell comprising a chimeric antigen receptor that binds a B-Cell antigen and a chimeric antigen receptor which binds a tumor antigen. See abstract. DRANOFF teaches introducing into said cell, a first vector including nucleic acid encoding the first CAR, and introducing into said cells a second vector including nucleic acid encoding the second CAR. Furthermore, DRANOFF teaches that the first chimeric antigen receptor (CAR) binds the B-Cell antigen CD 19 (see claim 3) and that the second CAR binds the solid tumor antigen TSHR (see claim 21).
Thus, DRANOFF teaches a composition of cells expressing two CARs (one that binds TSHR and the other binds CD19)
Regarding the polypeptides encoding the cytokines IL-6, IL-12, and IFNγ of present claim 1, the following references are applied.
OLADAPO is directed to CAR T-cells and teaches that CAR T-cells are efficacious against CD19-expressing B-cell malignancies. OLADAPO further teaches a different approach to optimization of CAR T-cells, which, through additional genetic modifications, results in an armored CAR T-cells are typically modified second generation CAR T-cells that have been further optimized to inducibly or constitutively secrete active cytokines. See abstract.
OLADAPO teaches that IL-6 is an inflammatory cytokine that is necessary for T-cell activation (see p. 415, left column, second paragraph); that IFNγ improves CAR T-cell cytotoxic function (see p. 413, right column); and that IL-12 enhances the cytotoxic ability of CD8 + T-cells and leads to increases in interferon-γ (IFN-γ) (see p. 413, right column, second sentence from top). Thus, OLADAPO teaches the significance of IL-6, IL-12, and IFNγ to T cell function.
CARSGEN is directed to a method for improving the function of an immune response cell and an immune response cell which expresses at least one receptor capable of binding to an antigen and type I interferon, in which the cell has a significant ability to kill tumours or pathogens and can be used for treating tumours and infectious diseases. See abstract. CARSGEN teaches that CAR-modified T-cell (CAR-T) cells targeting CD19 in clinical trials has been a great success in the treatment of B-cell leukemia. See p. 2, Background technique, first paragraph, of the English translation. CARSGEN teaches that cytokines have further immunomodulatory or anti-tumor activity, enhance the function of effector T cells and activated NK cells, or directly exert anti-tumor effects and thus, those skilled in the art will appreciate that the use of these cytokines will help the immune response cells to function better. See p. 13, 10th paragraph from the top of the English translation. CARSGEN teaches NFAT-controlled expression can be used to regulate the expression of cytokines such as IL12 in T lymphocytes. See p. 13, fourth paragraph from the top of the English translation.
Therefore, OLADAPO and CARSGEN teach that cytokines can armor a CAR T cell and make it more effective. Both further teach that the expression of these cytokines may be induced or controlled.
Overall, because DRANOFF teaches cells expressing two CARS, one binding TSHR and the other binding CD19 and OLADAPO and CARSGEN teach that cytokines such as IL-6, IL-12, and IFNγ enhance a CAR-T’s tumor killing function, it would have been obvious to combine the teachings of the cited references to arrive to the invention of present claims 1 and 35. There would have been a reasonable expectation of success considering that a composition comprising multiple vectors encoding a CAR binding TSHR, encoding a CAR binding CD19, and encoding inducible cytokines IL-6, IL-12, IFNγ are known to be effective in the treatment of cancer, as evidenced by the applied art.
Regarding claims 6 – 8 and 53 – 54, DRANOFF teaches that cells are transfected with the set of constructs to express both the B-cell antigen CAR and the solid tumor antigen CAR (see p. 20, lines 10 – 12) and the cells are human T cells (see p. 220, first paragraph).
Regarding claim 28, CARSGEN teaches that an inducible promoter is a controlled promoter and that a promoter is operably linked to a coding sequence if the promoter affects transcription or expression of the coding sequence. See p. 14, fourth paragraph from bottom and p. 6, fourth and third paragraph from the bottom. Because each of the vectors includes the coding sequences, it would be obvious that each of the vectors comprises a promoter comprising a binding site for a transcription modulator that can modulate expression of the coding sequence on each of the four vectors.
Regarding claim 32, CARSGEN teaches that because transcriptional expression of cytokines plays an important role in T cell activation, it was placed under the control of NFAT (Nuclear factor of activated T cells), such as NFAT6. See p. 13, fourth paragraph from the top, of the English translation.
Regarding claim 33, CARSGEN teaches that cytokines such as IFN-y secreted by immune response cells, and improve the survival cycle and anti-tumor effect of CAR immune response cells in vivo. See p. 13, second paragraph from top. Furthermore CARSGEN teaches that the immune response cell may further carry a coding sequence of a foreign cytokine; the cytokine includes, but not limited to, IL-12, IL-15 or IL-21 and the like. See p. 13, ninth paragraph from the top. Thus, it would have been obvious to place IL-6, IL-12, and IFNγ under the regulation of NFAT.
Regarding claim 34, CARSGEN teaches that the immune response cell may further carry a coding sequence of a foreign cytokine; the cytokine includes, but not limited to, IL-12. See p. 13, tenth paragraph from the top. CARSGEN also teaches an inducible promoter for use herein includes Hypoxia-Inducible Transcription factor-1α (HIF-1α). See p. 14, fourth paragraph from bottom, of the English translation.
Regarding claim 40, CARSGEN teaches a CD28 transmembrane region. See p. 23, fifth paragraph from bottom.
Regarding claim 41, CARSGEN teaches that the natural transmembrane portion of CD8α can also be used in the CAR. See p. 9, second paragraph from the bottom.
Regarding claim 50, DRANOFF teaches that the vector is a lentiviral vector. See p. 18, first paragraph.
2. Claims 5, 25, 36 – 38, 43 and 52 are rejected under 35 U.S.C. 103 as being unpatentable over DRANOFF in view of OLADAPO and CARSGEN as applied to claims 1, 6 – 8, 28, 32 – 35, 40 – 41, 50 and 53 – 54 above, and further in view of XIAO (WO 2017/167217 A1, published 10/05/2017; see PTO-892: Notice of References Cited of 01/15/2025).
XIAO is directed to pharmaceutical composition comprising human T cells comprising a nucleic
acid sequence encoding a chimeric antigen receptor (CAR). See claim 1. XIAO teaches a CAR targeting CD19. See line 41, p. 18. Furthermore, XIAO teaches that primary T cells were transduced with lentivirus including various CARs to establish different CAR T cell lines targeting different antigens, such as THSR and GUCY2C. See Construction of T cells, p. 31 and FIG. 1. XIAO teaches a composition for transfection and transduction of vectors comprising nucleic acid sequence/polynucleotides encoding CARs. See claim 1 and p. 16, lines 16 – 36.
Regarding claim 5, XIAO teaches that the CAR may include an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain. See abstract.
Regarding claim 25, XIAO discloses a CAR with a sequence that is identical to that of present SEQ ID NO: 8. See XIAO’s SEQ ID NO: 5 and Appendix (#1 of the alignments listed at the end of this Office Action).
Regarding claims 36 – 37, XIAO teaches that the intracellular domain of a costimulatory molecule selected from the group consisting of CD27, CD28, 4-lBB, OX40, CD30, CD40, PD-1, ICOS, lymphocyte function-associated antigen-1 (LFA-1) , CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, and any combination thereof. See p. 24, lines 14 – 17.
Regarding claims 38, XIAO teaches the sequence of SEQ ID NO: 127. XIAO’s SEQ ID NO: 22 is identical to present SEQ ID NO: 127. See Appendix (#2).
Regarding claim 43, XIAO teaches the sequence of SEQ ID NO: 34. XIAO’s SEQ ID NO: 21 discloses present SEQ ID NO: 34 with 100% identity. See Appendix.
Regarding claim 52, XIAO also teaches that primary T cells were transduced with lentivirus including various CARs to establish different CAR T cell lines targeting different antigens, such as THSR and GUCY2C. See Construction of T cells, p. 31 and FIG. 1.
3. Claims 24, 27, 39, 42, and 45 – 46 are rejected under 35 U.S.C. 103 as being unpatentable over DRANOFF in view of OLADAPO, CARSGEN, XIAO as applied to claims 1, 5 – 8, 2528, 32 – 38, 40 – 41, 43, 50 and 52 – 54 above, and further in view of WU (US 2018/153977-A1, published 06/07/201, 8; see PTO-892 of 01/15/2025), JUNE (WO 2012/079000 A1, published 6/14/2012; see PTO-892 of 01/15/2025), and SADELAIN (US2004043401-A1, published 03/04/2004; see PTO-892).
The teachings of DRANOFF, OLADAPO, and CARSGEN are discussed above and fully incorporated here.
WU is directed to a CAR with an antigen binding domain binds to CD19. See claims 10 – 11.
JUNE is directed to an isolated nucleic acid sequence encoding a CAR with an antigen binding domain binds to a tumor antigen such as CD 19. See claims 1, 6, and 9.
SADELAIN is directed to a nucleic acid polymer encoding a chimeric T cell receptor with a binding element that binds to CD19. See claims 1 – 6.
Regarding claims 24 and 27, WU teaches the sequence of SEQ ID NO: 5. WU’s SEQ ID NO: 43 is identical to present SEQ ID NO: 5 of present claims 24, 27, and 46. See Appendix (#4).
Regarding SEQ ID NO: 6 of claim 24, JUNE discloses the sequence of SEQ ID NO: 6. JUNE’s SEQ ID NO 20 is identical to present SEQ ID NO: 6. See Appendix (#5).
Regarding claim 39, SADELAIN teaches the sequence encoded by SEQ ID NO: 41. SADELAIN’s SEQ ID NO: 14 discloses the amino acid sequence of present SEQ ID NO: 41 with 100% identity. See Appendix (#6).
Regarding claim 42, JUNE teaches the sequence of SEQ ID NO: 37. JUNE’s SEQ ID NO: 22 is identical to present SEQ ID NO: 37 of present claim 42. See Appendix (#7).
Regarding claims 45 and 46, XIAO discloses the sequences of SEQ ID NOs: 11, 35, and 127 with 100% identity; JUNE discloses the sequence of SEQ ID NOs: 37 with 100% identity; SADELAIN teaches the sequence of SEQ ID NO: 41 with 100% identity; and WU teaches the sequence of SEQ ID NO: 5 with 100% identity as discussed above. See Appendix (#s 8, 9, 2, 10, 6, 4).
Because XIAO, WU, JUNE, and SADELAIN teach components of CARs that are effective at treating cancer, it would have been obvious combine different components of the CARs taught by the references to arrive to the CARs of present claims 24, 27, 42, and 45 – 46 with a reasonable expectation of success. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 (I) and (II).
Overall, because DRANOFF teaches CAR-T cells with a CAR binding CD19 and another CAR binding TSHR; OLADAPO and CARSGEN teach that cytokines such as IL-6, IL-12, and IFNγ enhance a CAR-T’s tumor killing function; and XIAO, WU, JUNE, and SADELAIN teach components of CARs that are effective at treating cancer, it would have been obvious to combine the teachings the cited references to arrive to the compositions of present claims 24, 27, 39, 42, and 45 – 46. There would have been a reasonable expectation of success considering that a composition comprising multiple vectors encoding multiple CARs binding TSHR and CD19 and encoding inducible cytokines IL-6, IL-12, IFNγ are known to be effective in the treatment of cancer, as evidenced by the applied art.
4. Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over DRANOFF in view of OLADAPO and CARSGEN as applied to claims 1, 6 – 8, 28, 32 – 35, 40 – 41, 50 and 53 – 54 above and further in view of XIAO 3 (WO2018064921-A1, published 04/12/2018; see PTO-892).
The teachings of DRANOFF, OLADAPO, and CARSGEN are discussed above and fully incorporated here.
XIAO 3 is directed to an isolated nucleic acid sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain that binds to FZD10, TSHR, PRLR, Muc17, GUCY2C, or CD207. See claim 1. XIAO 3 teaches the sequence of present SEQ ID NO: 535 of present claim 26 with 100% identity. See Appendix.
Thus, because DRANOFF teaches CAR-T cells with a CAR binding CD19 and another CAR binding TSHR; OLADAPO and CARSGEN teach that cytokines such as IL-6, IL-12, and IFNγ enhance a CAR-T’s tumor killing function; and XIAO 3 teaches a CAR that is effective at treating cancer, it would have been obvious to combine the teachings the cited references to arrive to the composition of present claim 26. There would have been a reasonable expectation of success considering that a composition comprising multiple vectors encoding multiple CARs binding TSHR and CD19 and encoding inducible cytokines IL-6, IL-12, IFNγ are known to be effective in the treatment of cancer, as evidenced by the applied art.
5. Claim 29 is rejected under 35 U.S.C. 103 as being unpatentable over DRANOFF in view of OLADAPO and CARSGEN as applied to claims 1, 6 – 8, 28, 32 – 35, 40 – 41, 50 and 53 – 54 above and further in view of MORGAN (WO2010126766-A1, published 11/04/2010; see PTO-892).
The teachings of DRANOFF, OLADAPO, and CARSGEN are discussed above and fully incorporated here.
MORGAN is directed to an isolated or purified nucleic acid comprising a nucleotide sequence encoding a nuclear factor of activated T-cells (NFAT) promoter operatively associated with a nucleotide sequence encoding IL- 12.
Regarding claim 29, MORGAN teaches the sequence of SEQ ID NO: 332. MORGAN’s SEQ ID NO: 4 discloses the sequence of present SEQ ID NO: 332 with 100% identity. See Appendix (#12).
Thus, because DRANOFF teaches CAR-T cells with a CAR binding CD19 and another CAR binding TSHR; OLADAPO and CARSGEN teach that cytokines such as IL-6, IL-12, and IFNγ enhance a CAR-T’s tumor killing function; and MORGAN teaches a NFAT promoter effective at inducing cytokine expression, it would have been obvious to combine the teachings the cited references to arrive to the composition of present claim 29. There would have been a reasonable expectation of success considering that a composition comprising multiple vectors encoding multiple CARs binding TSHR and CD19 and encoding inducible cytokines IL-6, IL-12, IFNγ are known to be effective in the treatment of cancer, as evidenced by the applied art.
6. Claims 30 – 32 are rejected under 35 U.S.C. 103 as being unpatentable over DRANOFF in view of OLADAPO and CARSGEN as applied to claims 1, 6 – 8, 28, 32 – 35, 40 – 41, 50 and 53 – 54 above and further in view of JUILLERAT (WO2015092024-A2, published 06/25/2015; see PTO-892).
The teachings of DRANOFF, OLADAPO, and CARSGEN are discussed above and fully incorporated here.
According to the present specification, “a VHL-interaction domain of Hif1a may be linked to a polynucleotide encoding a CAR such that the expression of the CAR can be induced by hypoxia” (paragraph 0250 of the pre-grant publication).
JUILLERAT is directed to immune cells are engineered with chimeric antigen receptors, which be activated by the combination of hypoxia and ligand extracellular binding as input signals. See abstract. JUILLERAT teaches a protein that is sensitive to hypoxia by being under the control of a hypoxia inducible promoter (see claim 16) and that the response to said hypoxia condition is triggered by the alpha hypoxia inducible factor 1 (HIF-1α). JUILLERAT teaches the sequence of SEQ ID NO: 457 of present claim. JUILLERAT’s SEQ ID NO: 22 is identical to present SEQ ID NO: 457. See Appendix (#13).
Because CARSGEN teaches the modulating the expression of cytokines and JUILLERAT teaches the modulation of protein expression using Hif-1α, it would have been obvious to modify CARSGEN’s gene with JUILLERAT’s Hif-1α promoter to arrive to the inventions of 30 – 32. There would have been a reasonable expectation of success considering that the cytokine expression modulation using inducible promoters such as Hif-1α has been known in the art, especially involving CAR-T cells, as evidenced by the applied prior art.
Overall, because DRANOFF teaches CAR-T cells with a CAR binding CD19 and another CAR binding TSHR; OLADAPO and CARSGEN teach that cytokines such as IL-6, IL-12, and IFNγ enhance a CAR-T’s tumor killing function; and JUILLERAT teaches a HIF-1α binding domain, it would have been obvious to combine the teachings the cited references to arrive to the composition of present claims 30 - 32. There would have been a reasonable expectation of success considering that a composition comprising multiple vectors encoding multiple CARs binding TSHR and CD19 and encoding inducible cytokines IL-6, IL-12, IFNγ are known to be effective in the treatment of cancer, as evidenced by the applied art.
7. Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over DRANOFF in view of OLADAPO and CARSGEN as applied to claims 1, 6 – 8, 28, 32 – 35, 40 – 41, 50 and 53 – 54 above and further in view of ORENTAS (WO2013059593-A1, published 04/25/2013; see PTO-892).
The teachings of DRANOFF, OLADAPO, and CARSGEN are discussed above and fully incorporated here.
ORENTAS is directed to a chimeric antigen receptor (CAR) and methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal . See abstract. ORENTAS teaches a CAR having the sequence of SEQ ID NO: 30. ORENTAS’ SEQ ID NO: 33 is identical to present SEQ ID NO: 30 of present claim 44. See Appendix (#14).
Thus, because DRANOFF teaches CAR-T cells with a CAR binding CD19 and another CAR binding TSHR; OLADAPO and CARSGEN teach that cytokines such as IL-6, IL-12, and IFNγ enhance a CAR-T’s tumor killing function; and ORENTAS teaches a CAR that is effective at treating cancer, it would have been obvious to combine the teachings the cited references to arrive to the composition of present claims 44. There would have been a reasonable expectation of success considering that a composition comprising multiple vectors encoding multiple CARs binding TSHR and CD19 and encoding inducible cytokines IL-6, IL-12, IFNγ are known to be effective in the treatment of cancer, as evidenced by the applied art.
8. Claim 47 is rejected under 35 U.S.C. 103 as being unpatentable over DRANOFF in view of OLADAPO and CARSGEN as applied to claims 1, 6 – 8, 28, 32 – 35, 40 – 41, 50 and 53 – 54 above and further in view of RALPH (WO200188097-A1, published 11/22/2001; see PTO-892).
The teachings of DRANOFF, OLADAPO, and CARSGEN are discussed above and fully incorporated here.
RALPH is directed to an immunostimulatory molecule and animal cells cultured in the presence of at least one interferon (IFN) for a time and under conditions sufficient to enhance the antigen presenting function of said cells. Also disclosed are immunopotentiating compositions and their use for treatment and/or prophylaxis of a disease or condition. See abstract. RALPH also teaches the structures of interleukins. RALPH teaches the sequence of SEQ ID NO: 287 with 100% identity. See Appendix (#15).
Thus, because DRANOFF teaches CAR-T cells with a CAR binding CD19 and another CAR binding TSHR; OLADAPO and CARSGEN teach that cytokines such as IL-6, IL-12, and IFNγ enhance a CAR-T’s tumor killing function; and RALPH teaches a cytokine having the sequence of SEQ ID NO: 287, it would have been obvious to combine the teachings the cited references to arrive to the composition of present claims 47. There would have been a reasonable expectation of success considering that a composition comprising multiple vectors encoding multiple CARs binding TSHR and CD19 and encoding inducible cytokines IL-6, IL-12, IFNγ are known to be effective in the treatment of cancer, as evidenced by the applied art.
9. Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over DRANOFF in view of OLADAPO and CARSGEN as applied to claims 1, 6 – 8, 28, 32 – 35, 40 – 41, 50 and 53 – 54 above and further in view of JENSEN (WO200136001-A2, published 05/25/2001; see PTO-892).
The teachings of DRANOFF, OLADAPO, and CARSGEN are discussed above and fully incorporated here.
JENSEN is directed to a conjugate exhibiting interferon gamma activity that may be used for treatment of various diseases. See abstract. JENSEN teaches an identical sequence to that of present SEQ ID NO: 328 of present claim 48. See Appendix (#16).
Thus, because DRANOFF teaches mixed CAR-T cells with a CAR binding CD19 and another CAR binding TSHR; OLADAPO and CARSGEN teach that cytokines such as IL-6, IL-12, and IFNγ enhance a CAR-T’s tumor killing function; and JENSEN teaches a cytokine having the sequence of SEQ ID NO: 328, it would have been obvious to combine the teachings the cited references to arrive to the composition of present claims 48. There would have been a reasonable expectation of success considering that a composition comprising multiple vectors encoding multiple CARs binding TSHR and CD19 and encoding inducible cytokines IL-6, IL-12, IFNγ are known to be effective in the treatment of cancer, as evidenced by the applied art.
10. Claims 49 and 51 are rejected under 35 U.S.C. 103 as being unpatentable over DRANOFF in view of OLADAPO and CARSGEN as applied to claims 1, 6 – 8, 28, 32 – 35, 40 – 41, 50 and 53 – 54 above and further in view of FROST (WO 2018136566 A1, published 07/26/2018; see PTO-892).
The teachings of DRANOFF, OLADAPO, and CARSGEN are discussed above and fully incorporated here.
FROST is directed to methods for genetically modifying and expanding immune cells ex vivo, especially for use in cell-based adoptive immunotherapy. See abstract. FROST teaches that the base media in the expansion step, as well as the activation and the transduction steps, can be supplemented with cytokines in the culturing of cells. See paragraph 0052.
Regarding claim 49, FROST teaches the sequence of SEQ ID NO: 310. FROST’s SEQ ID NO: 36 is identical to present SEQ ID NO: 310 of present claim 49. See Appendix (#17).
Regarding claim 51, FROST teaches that T cells and/or NK cells can be transduced with different ratios of replication incompetent recombinant retroviral or lentiviral particles to cells, referred to as the multiplicity of infection (MOI), such as 0.25, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 on the low end of the range and 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 on the high end of the range. See paragraph 0075. Thus, FROST teaches MOI of 10:1 (10) and 1:1 (1).
Thus, because DRANOFF teaches mixed CAR-T cells with a CAR binding CD19 and another CAR binding TSHR; OLADAPO and CARSGEN teach that cytokines such as IL-6, IL-12, and IFNγ enhance a CAR-T’s tumor killing function; and FROST teaches cytokines and methods of transducing T cells, it would have been obvious to combine the teachings the cited references to arrive to the composition of present claims 49 and 51. There would have been a reasonable expectation of success considering that a composition comprising multiple vectors encoding multiple CARs binding TSHR and CD19 and encoding inducible cytokines IL-6, IL-12, IFNγ are known to be effective in the treatment of cancer, as evidenced by the applied art.
Response to Arguments
On p. 9, second paragraph – p. 10, last paragraph, of the reply of 12/10/2025, Applicant argues that IL-6 and IFNγ are known contributors to CRS and that KONERU and OLADAPO teach away from combining IL-6 and IL- 12 in a single composition for transfecting or transducing T cells, as both references disclose IL- 6- and IFNy-induced toxicities, such as CRS, particularly severe CRS, observed with their IL-12- secreting CAR-T cells.
Applicant’s arguments have been fully considered but not found persuasive because the cited references also teach the advantages of the cytokines IL-6, IL-12, and IFNy to CAR T therapy, OLADAPO does not mention CRS, and KONERU teaches ways to mitigate CRS as discussed of record.
OLADAPO states that “[m]ost importantly, none of the previously described toxicities were seen in mice treated with our IL-12 armored CAR T-cell. However, it should be noted that mouse models do not completely recapitulate IL-12 toxicity in humans.” See p. 414, left column, first paragraph. Thus, OLADAPO emphasizes that the armored CAR T cell is safer than the alternative at the time of the reference but acknowledges that more studies are needed to fully assess its safety in humans. Therefore, it would have been obvious at the effective filing date of present independent claim 1 to combine CARs with cytokines to modulate the tumor microenvironment to improve CAR T-cell cytotoxic function as taught by OLADAPO (see p. 413, right column and p. 414, Figure 1).
On p. 11, Applicant argues that the cited references of record teach constitutively expressed proteins. However, OLADAPO teaches that “[t]hrough additional genetic modifications, these resultant armored CAR T-cells are typically modified second generation CAR T-cells that have been further optimized to inducibly or constitutively secrete active cytokines” (see abstract). Thus, OLADAPO teaches that the expression of the cytokines may be induced or constitutive.
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.
11. Claims 1, 5 – 8, and 24 – 54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 7 – 10, and 18 – 20 of U.S. Patent No. 11,944,645 in view of DRANOFF, OLADAPO, CARSGEN, XIAO, WU, JUNE, SADELAIN, XIAO 3, MORGAN, JUILLERAT, ORENTAS, RALPH, JENSEN, and FROST.
The combined teachings of the prior art above render obvious every claim for the reasons discussed above, all incorporated here. Therefore, the addition of the patented claims only further supports this finding of obviousness.
Patented claim 1 recites a method of enhancing an anti-tumor effect of a lymphocyte; patented claim 8 recites a CAR; and patented claim 19 recites a cytokine IL-6, IL-7, IL-15, IL-12, or IFNγ”; antigen-binding domain binds a tumor antigen comprising TSHR, CD19, CD123, CD22, CD30, CD171, CS-1, CLL-1, CD33, EGFRvIII . . . ; and patented claim 20 recites a first population of T cells comprising a CAR binding a cell surface molecule of a white blood cell (WBC) and a second population of T cells comprising a CAR binding a solid tumor antigen. Thus, the patented claims, when combined with the cited art above, render obvious the present claims for the reasons discussed above.
12. Claims 1, 5 – 8, and 24 – 54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4 – 6, 8 – 13, 15 – 18 of U.S. Patent No. 11,788,072 in view of DRANOFF, OLADAPO, CARSGEN, XIAO, WU, JUNE, SADELAIN, XIAO 3, MORGAN, JUILLERAT, ORENTAS, RALPH, JENSEN, and FROST.
The combined teachings of the prior art above render obvious every claim for the reasons discussed above, all incorporated here. Therefore, the addition of the patented claims only further supports this finding of obviousness.
Patented claim 6 recites a CAR; patented claim 9 recites that the antigen binding domain binds to a tumor antigen comprising TSHR, CD19, CD123, CD22, CD30, CD171, CS-1, CLL-1, CD33, EGFRvIII, . . . ; and patented claims 12 and 13 recite that the modified cell is engineered to express and secrete a therapeutic agent IL-12, IL-6, or IFN-γ. Thus, the patented claims, when combined with the cited art above, render obvious the present claims for the reasons discussed above.
13. Claims 1, 5 – 8, and 24 – 54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, 7 – 9, 15, 16, 18, 21, and 22 of U.S. Patent No. 11,104,732 in view of DRANOFF, OLADAPO, CARSGEN, XIAO, WU, JUNE, SADELAIN, XIAO 3, MORGAN, JUILLERAT, ORENTAS, RALPH, JENSEN, and FROST.
The combined teachings of the prior art above render obvious every claim for the reasons discussed above, all incorporated here. Therefore, the addition of the patented claims only further supports this finding of obviousness.
Patented claims 3 and 4 recites that the modified T cell is engineered to express and secrete a therapeutic agent, wherein the therapeutic agent comprises at least one of IL-33, IL-1β, TNFα, MALP-2, IL1, IL17, G-CSF or GM-CSF, IL-6, IL-12, and IFN-γ; patented claim 7 recites a CAR; and patented claim 8 recites that the antigen-binding domain binds a tumor antigen comprising TSHR, CD19, CD123, CD22, CD30, CD171, CS-1, CLL-1, CD33, EGFRvIII . . . Thus, the patented claims, when combined with the cited art above, render obvious the present claims for the reasons discussed above.
14. Claims 1, 5 – 8, and 24 – 54 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5 – 10 of U.S. Patent No. 11,739,136 in view of DRANOFF, OLADAPO, CARSGEN, XIAO, WU, JUNE, SADELAIN, XIAO 3, MORGAN, JUILLERAT, ORENTAS, RALPH, JENSEN, and FROST.
The combined teachings of the prior art above render obvious every claim for the reasons discussed above, all incorporated here. Therefore, the addition of the patented claims only further supports this finding of obviousness.
Patented claim 3 recites that a modified cell comprising a CAR; patented claim 6 recites that the tumor antigen comprising TSHR, CD19, CD123, CD22, CD30, CD171, CS-1, CLL-1, CD33, EGFRvIII, . . . ; and patented claim 10 recites that the modified cell is engineered to express and secrete IL-12, IL-6, or IFN-γ. Thus, the patented claims, when combined with the cited art above, render obvious the present claims for the reasons discussed above.
15. Claims 1, 5 – 8, and 24 – 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims 1, 5 – 8, 18, and 19 of copending Application No. 18/043,021 in view of DRANOFF, OLADAPO, CARSGEN, XIAO, WU, JUNE, SADELAIN, XIAO 3, MORGAN, JUILLERAT, ORENTAS, RALPH, JENSEN, and FROST.
The combined teachings of the prior art above render obvious every claim for the reasons discussed above, all incorporated here. Therefore, the addition of the copending claims only further supports this finding of obviousness.
Copending claim 1 recites a method of enhancing T cell response, the method comprising: introducing a nucleic acid encoding a chimeric antigen receptor (CAR); copending claim 6 recites that the tumor antigen comprises TSHR, CD19, CD123, CD22, CD30, CD171, CS-1, CLL-1, CD33, EGFRvIII, . . . ; copending claim 18 recites that the modified T cells comprise an exogenous nucleic acid encoding a therapeutic agent, and the therapeutic agent comprises one or more of IL-1P, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IL-1Ra, IL-2R, IFNy, MIP-In, MIP-IP, MCP-1, TNFa, GM-CSF, GCSF, CXCL9, CXCL10, CXCR factors, VEGF, RANTES, EOTAXIN, EGF, HGF, FGF-P, and ferritin. Thus, the pending claims, when combined with the cited art above, render obvious the present claims for the reasons discussed above.
This is a provisional nonstatutory double patenting rejection.
16. Claims 1, 5 – 8, and 24 – 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims 1, 9 – 16, and 19 of copending Application No. 18/156,482 in view of DRANOFF, OLADAPO, CARSGEN, XIAO, WU, JUNE, SADELAIN, XIAO 3, MORGAN, JUILLERAT, ORENTAS, RALPH, JENSEN, and FROST.
The combined teachings of the prior art above render obvious every claim for the reasons discussed above, all incorporated here. Therefore, the addition of the copending claims only further supports this finding of obviousness.
Copending claim 1 recites a method of promoting maintenance of T cell population expressing a chimeric antigen receptor (CAR); copending claim 9 recites that the CAR binds to tMUC 1, PRLR, CLCA1, MUC12, GUCY2C, GPR35, CR1L, MUC 17, TMPRSS11B, MUC21, TMPRSS11E, CD207, SLC30A8, CFC1, SLC12A3, SSTR1, GPR27, FZD10, TSHR, SIGLEC15, SLC6A3, KISS1R, CLDN18.2, QRFPR, GPR119, CLDN6, UPK2, ADAM12, SLC45A3, ACPP, MUC21, MUC16, MS4A12, ALPP, CEA, EphA2, FAP, GPC3, IL13-Ra2, Mesothelin, PSMA, ROR1, VEGFR-II, GD2, FR-a, ErbB2, EpCAM, EGFRvIII,B7-H3, or EGFR; copending claims 13 – 15 recites that the population of T cells is engineered to express and secrete a therapeutic agent such as IL-6 or IFN-y or IL-12 or a combination thereof; and copending 19 – 20 recites that the population of T cells further comprises an additional CAR binding a white blood cell antigen, wherein the white blood cell antigen is CD19, CD22, CD20, BCMA, CD5,CD7,CD2, CD16, CD56, CD30, CD14, CD68, CD11b, CD18, CD169, CD1c, CD33, CD38, CD138, or CD13. Thus, the copending claims, when combined with the cited art above, render obvious the present claims for the reasons discussed above.
This is a provisional nonstatutory double patenting rejection.
16. Claims 1, 5 – 8, and 24 – 54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims 1, 3, 5, 7 – 10, 12, and 15 of copending Application No. 17/996,589 in view of DRANOFF, OLADAPO, CARSGEN, XIAO, WU, JUNE, SADELAIN, XIAO 3, MORGAN, JUILLERAT, ORENTAS, RALPH, JENSEN, and FROST.
The combined teachings of the prior art above render obvious every claim for the reasons discussed above, all incorporated here. Therefore, the addition of the copending claims only further supports this finding of obviousness.
Copending claim 1 recites a method of enhancing activation of modified cells, the method comprising: obtaining modified cells comprising chimeric antigen receptor (CAR) T cells, wherein the CAR of the CAR T cells comprises a binding domain, a transmembrane domain, and an intracellular domain, the binding domain binding a solid tumor antigen; obtaining a bispecific antibody, wherein the bispecific antibody comprises a first binding domain binding CD3 and a second binding domain binding CD19, CD20, CD22, or BCMA; contacting the CAR T cells with B cells and the bispecific antibody, thereby activating the modified cells, wherein level of activation of the CAR T cells is higher than level of activation in CAR T cells that are contacted with B cells without the bispecific antibody.
Copending claim 5 recites that the solid tumor antigen comprises tMUC1, PRLR, CLCA1, MUC12, GUCY2C, GPR35, CR1L, MUC 17, TMPRSS11B, MUC21, TMPRSS11E, CD207, SLC30A8, CFC1, SLC12A3, SSTR1, GPR27, FZD10, TSHR, SIGLEC15, SLC6A3, KISS1R, QRFPR, GPR119, CLDN6, UPK2, ADAM12, SLC45A3, ACPP, MUC21, MUC16, MS4A12, ALPP, CEA, EphA2, FAP, GPC3, IL13-Ra2, Mesothelin, PSMA, ROR1, VEGFR-II, GD2, FR-a, ErbB2, EpCAM, EGFRvIII,B7-H3,CLDN18.2, MAGE A4, MSLN, CD205, or EGFR.
Copending claim 15 recites that the modified cells comprise an exogenous polynucleotide encoding a therapeutic agent comprising IL-1 P, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, IL-1Ra, IL-2R, IFNy.
Thus, the copending claims, when combined with the cited art above, render obvious the present claims for the reasons discussed above.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
On page 14 – 15 of the reply of 12/10/2025, Applicant argues that none of the cited patents or applications teach or suggest the claimed composition.
However, the rejections are maintained as discussed above.
Conclusion
Claims 1, 5 – 8, and 24 – 54 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
APPENDIX
1. Alignment with SEQ ID NO: 8
RESULT 1
BEJ15803
(NOTE: this sequence has 35 duplicates in the database searched.
See complete list at the end of this report)
ID BEJ15803 standard; protein; 244 AA.
XX
AC BEJ15803;
XX
DT 16-NOV-2017 (first entry)
XX
DE Anti-TSHR single-chain fragment variable (scFv), SEQ ID 5.
XX
KW TSH receptor; TSHR protein; cancer; cell therapy; cytostatic;
KW immune stimulation; single domain antibody; t-lymphocyte; therapeutic;
KW thyrotropin receptor.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2017167217-A1.
XX
CC PD 05-OCT-2017.
XX
CC PF 30-MAR-2017; 2017WO-CN078740.
XX
PR 01-APR-2016; 2016US-0317261P.
XX
CC PA (INNO-) INNOVATIVE CELLULAR THERAPEUTICS CO LTD.
XX
CC PI Xiao L, Wu Z, Pu C, Cao Z, Sun H, Bi M;
XX
DR WPI; 2017-68343K/73.
XX
CC PT Pharmaceutical composition for stimulating T cell-mediated immune
CC PT response to cell population expressing antigen and for treating cancer,
CC PT comprises human T cells comprising nucleic acid sequence encoding
CC PT chimeric antigen receptor (CAR).
XX
CC PS Claim 2; SEQ ID NO 5; 62pp; English.
XX
CC The present invention relates to a pharmaceutical composition useful for
CC stimulating T cell-mediated immune response to cell population expressing
CC antigen. The invention further relates to: (1) a method for stimulating a
CC T cell-mediated immune response to a cell population expressing the
CC antigen; and (2) a modified T cell comprising a nucleic acid sequence
CC encoding chimeric antigen receptor (CAR). The invention also relates to a
CC use of CAR modified cells for treating cancer. The present sequence
CC represents an anti-thyrotropin receptor (TSHR) single-chain fragment
CC variable (scFv), which is useful for the construction of CAR of the
CC invention.
XX
SQ Sequence 244 AA;
Query Match 100.0%; Score 1306; Length 244;
Best Local Similarity 100.0%;
Matches 244; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QSVLTQPPSVSAAPGQKVTISCSGSSSDIGSNYVSWYQQFPGTAPKLLIYDNNKRPSAIP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSVLTQPPSVSAAPGQKVTISCSGSSSDIGSNYVSWYQQFPGTAPKLLIYDNNKRPSAIP 60
Qy 61 DRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSRLGIAVFGGGTQLTVLGGGGSGGGGS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DRFSGSKSGTSATLGITGLQTGDEADYYCGTWDSRLGIAVFGGGTQLTVLGGGGSGGGGS 120
Qy 121 GGGGSEVQLVQSGAEVKKPGQSLKISCKASGYSLTDNWIGWVRQKPGKGLEWMGIIYPGD 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GGGGSEVQLVQSGAEVKKPGQSLKISCKASGYSLTDNWIGWVRQKPGKGLEWMGIIYPGD 180
Qy 181 SDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCVGLDWNYNPLRYWGPGTLV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SDTRYSPSFQGQVTISADKSINTAYLQWSSLKASDTAIYYCVGLDWNYNPLRYWGPGTLV 240
Qy 241 TVSS 244
||||
Db 241 TVSS 244
2. Alignment with SEQ ID NO: 127
BEJ15820
ID BEJ15820 standard; protein; 42 AA.
XX
AC BEJ15820;
XX
DT 16-NOV-2017 (first entry)
XX
DE CAR construction related costimulatory signaling region, SEQ ID 22.
XX
KW cancer; cell therapy; cytostatic; immune stimulation; t-lymphocyte;
KW therapeutic.
XX
OS Unidentified.
XX
CC PN WO2017167217-A1.
XX
CC PD 05-OCT-2017.
XX
CC PF 30-MAR-2017; 2017WO-CN078740.
XX
PR 01-APR-2016; 2016US-0317261P.
XX
CC PA (INNO-) INNOVATIVE CELLULAR THERAPEUTICS CO LTD.
XX
CC PI Xiao L, Wu Z, Pu C, Cao Z, Sun H, Bi M;
XX
DR WPI; 2017-68343K/73.
XX
CC PT Pharmaceutical composition for stimulating T cell-mediated immune
CC PT response to cell population expressing antigen and for treating cancer,
CC PT comprises human T cells comprising nucleic acid sequence encoding
CC PT chimeric antigen receptor (CAR).
XX
CC PS Disclosure; SEQ ID NO 22; 62pp; English.
XX
CC The present invention relates to a pharmaceutical composition useful for
CC stimulating T cell-mediated immune response to cell population expressing
CC antigen. The invention further relates to: (1) a method for stimulating a
CC T cell-mediated immune response to a cell population expressing the
CC antigen; and (2) a modified T cell comprising a nucleic acid sequence
CC encoding chimeric antigen receptor (CAR). The invention also relates to a
CC use of CAR modified cells for treating cancer. The present sequence
CC represents a costimulatory signaling region, which is useful for the
CC construction of CAR of the invention.
XX
SQ Sequence 42 AA;
ALIGNMENT:
Query Match 100.0%; Score 232; Length 42;
Best Local Similarity 100.0%;
Matches 42; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 42
||||||||||||||||||||||||||||||||||||||||||
Db 1 KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 42
3. Alignment with SEQ ID NO: 34
RESULT 4
BEJ15819
(NOTE: this sequence has 86 duplicates in the database searched.
See complete list at the end of this report)
ID BEJ15819 standard; protein; 69 AA.
XX
AC BEJ15819;
XX
DT 16-NOV-2017 (first entry)
XX
DE CAR construction related hinge and transmembrane domain, SEQ ID 21.
XX
KW cancer; cell therapy; cytostatic; immune stimulation; t-lymphocyte;
KW therapeutic.
XX
OS Unidentified.
XX
CC PN WO2017167217-A1.
XX
CC PD 05-OCT-2017.
XX
CC PF 30-MAR-2017; 2017WO-CN078740.
XX
PR 01-APR-2016; 2016US-0317261P.
XX
CC PA (INNO-) INNOVATIVE CELLULAR THERAPEUTICS CO LTD.
XX
CC PI Xiao L, Wu Z, Pu C, Cao Z, Sun H, Bi M;
XX
DR WPI; 2017-68343K/73.
XX
CC PT Pharmaceutical composition for stimulating T cell-mediated immune
CC PT response to cell population expressing antigen and for treating cancer,
CC PT comprises human T cells comprising nucleic acid sequence encoding
CC PT chimeric antigen receptor (CAR).
XX
CC PS Disclosure; SEQ ID NO 21; 62pp; English.
XX
CC The present invention relates to a pharmaceutical composition useful for
CC stimulating T cell-mediated immune response to cell population expressing
CC antigen. The invention further relates to: (1) a method for stimulating a
CC T cell-mediated immune response to a cell population expressing the
CC antigen; and (2) a modified T cell comprising a nucleic acid sequence
CC encoding chimeric antigen receptor (CAR). The invention also relates to a
CC use of CAR modified cells for treating cancer. The present sequence
CC represents a hinge and transmembrane domain, which is useful for the
CC construction of CAR of the invention.
XX
SQ Sequence 69 AA;
Query Match 100.0%; Score 272; Length 69;
Best Local Similarity 100.0%;
Matches 50; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIY 50
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIY 50
4. Alignment with SEQ ID NO: 5
RESULT 1
BFJ31747
(NOTE: this sequence has 41 duplicates in the database searched.
See complete list at the end of this report)
ID BFJ31747 standard; protein; 242 AA.
XX
AC BFJ31747;
XX
DT 26-JUL-2018 (first entry)
XX
DE ScFv humanized CD19, SEQ ID 43.
XX
KW B-lymphocyte antigen CD19; adenocarcinoma; antibody therapy;
KW basal cell carcinoma; breast tumor; cancer; carcinoma; chondrosarcoma;
KW colon tumor; cytostatic; ewing sarcoma; fibrosarcoma;
KW hepatocellular carcinoma; immunotherapy; leiomyosarcoma; liposarcoma;
KW lung tumor; medullary thyroid cancer; mesothelioma; myxosarcoma;
KW osteosarcoma; ovary tumor; pancreas tumor; papillary thyroid tumor;
KW prostate tumor; rhabdomyosarcoma; sarcoma; single chain antibody;
KW squamous cell carcinoma; sweat gland disease; therapeutic.
XX
OS Unidentified.
XX
CC PN US2018153977-A1.
XX
CC PD 07-JUN-2018.
XX
CC PF 22-JAN-2018; 2018US-00876538.
XX
PR 24-JUL-2015; 2015WO-CN084991.
PR 05-JAN-2017; 2017WO-CN070208.
XX
CC PA (INNO-) INNOVATIVE CELLULAR THERAPEUTICS CO LTD.
XX
CC PI Wu Z, Liu Z, Xiao L, Pu C, Cao Z;
XX
DR WPI; 2018-45006Q/42.
XX
CC PT New isolated nucleic acid sequence encoding humanized antibody or its
CC PT antigen-binding fragment useful in composition for treating tumor e.g.
CC PT sarcoma, carcinoma, fibrosarcoma, myxosarcoma, liposarcoma,
CC PT chondrosarcoma, or osteosarcoma.
XX
CC PS Claim 12; SEQ ID NO 43; 45pp; English.
XX
CC The present invention relates to a novel isolated nucleic acid sequence
CC encoding humanized antibody or its antigen-binding fragment useful in a
CC composition for treating tumor. The invention further relates to: (1) an
CC expression vector comprising the isolated nucleic acid sequence operably
CC linked to control sequences recognized by a host cell transfected with
CC the expression vector; (2) a host cell comprising the expression vector;
CC (3) a chimeric antigen receptor (CAR) comprising a single-chain variable
CC fragment (scFv); (4) a vector comprising a nucleic acid sequence encoding
CC the CAR; (5) a cell comprising the CAR; and (6) a composition comprising
CC a population of the cell. The isolated nucleic acid sequence is useful in
CC the composition for treating a CD19-expressing tumor, and stimulating an
CC anti-tumor immune response to the tumor, where the tumor is chosen from
CC sarcoma, carcinoma, fibrosarcoma, myxosarcoma, liposarcoma,
CC chondrosarcoma, osteosarcoma, and other sarcomas, synovioma,
CC mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon
CC carcinoma, lymphoid malignancy, pancreatic cancer, breast cancer, lung
CC cancers, ovarian cancer, prostate cancer, hepatocellular carcinoma,
CC squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat
CC gland carcinoma, medullary thyroid carcinoma, and papillary thyroid
CC carcinoma. The present sequence represents a ScFv humanized CD19 useful
CC for homology comparison.
XX
SQ Sequence 242 AA;
Query Match 100.0%; Score 1283; Length 242;
Best Local Similarity 100.0%;
Matches 242; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDISKYLNWYQQKPGKAPKLLIYHTSRLHSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDISKYLNWYQQKPGKAPKLLIYHTSRLHSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTLPYTFGQGTKVEIKGGGGSGGGGSGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTLPYTFGQGTKVEIKGGGGSGGGGSGGG 120
Qy 121 GSEVQLVESGGGLVQPGGSLRLSCAASGVSLPDYGVSWVRQAPGKGLEWVSVIWGSETTY 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSEVQLVESGGGLVQPGGSLRLSCAASGVSLPDYGVSWVRQAPGKGLEWVSVIWGSETTY 180
Qy 181 YNSALKSRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKHYYYGGSYAMDYWGQGTLVTV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YNSALKSRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAKHYYYGGSYAMDYWGQGTLVTV 240
Qy 241 SS 242
||
Db 241 SS 242
5. Alignment with SEQ ID NO: 6
RESULT 1
AZX24807
(NOTE: this sequence has 443 duplicates in the database searched.
See complete list at the end of this report)
ID AZX24807 standard; protein; 242 AA.
XX
AC AZX24807;
XX
DT 02-AUG-2012 (first entry)
XX
DE Murine anti-CD19 antibody scFv SEQ ID NO:20.
XX
KW B-lymphocyte antigen CD19; CD19 protein; cancer; cell therapy;
KW chimeric protein; cytostatic; gene expression; gene therapy;
KW immune stimulation; leukemia; lymphoma; monoclonal antibody;
KW protein therapy; single chain antibody; therapeutic.
XX
OS Mus sp.
XX
CC PN WO2012079000-A1.
XX
CC PD 14-JUN-2012.
XX
CC PF 09-DEC-2011; 2011WO-US064191.
XX
PR 09-DEC-2010; 2010US-0421470P.
PR 29-JUN-2011; 2011US-0502649P.
XX
CC PA (UPEN ) UNIV PENNSYLVANIA.
XX
CC PI June CH, Levine BL, Porter DL, Kalos MD;
XX
DR WPI; 2012-G81463/42.
DR N-PSDB; AZX24801.
XX
CC PT New isolated nucleic acid sequence encoding a chimeric antigen receptor
CC PT containing antigen binding domain, transmembrane domain, costimulatory
CC PT signaling region, and zeta signaling domain, useful for treating cancer,
CC PT and lymphocytic leukemia.
XX
CC PS Example 2; SEQ ID NO 20; 131pp; English.
XX
CC The invention relates to a novel isolated nucleic acid sequence encoding
CC a chimeric antigen receptor (CAR) useful for treating cancer, and
CC lymphocytic leukemia selected from refractory CD19+ leukemia and lymphoma
CC in a patient. The CAR of SEQ ID NO: 12 (AZX24799) comprises an antigen
CC binding domain, a transmembrane domain, a costimulatory signaling region,
CC and a CD3 zeta signaling domain of SEQ ID NO: 24 (AZX24811). The
CC invention independently claims for: a cell and a vector comprising a
CC nucleic acid sequence of SEQ ID NO: 8 (AZX24795) encoding the CAR; a
CC method of stimulating a T cell-mediated immune response to a target cell
CC population or tissue in a mammal; a method of providing an anti-tumor
CC immunity in a mammal; a method of treating a mammal having a disease,
CC disorder or condition associated with an elevated expression of a tumor
CC antigen; a method of generating a persisting population of genetically
CC engineered T cells in a patient diagnosed with cancer; and a method of
CC expanding a population of genetically engineered T cells in a patient
CC diagnosed with cancer. The isolated nucleic acid sequence treats a
CC patient who is resistant to at least one chemotherapeutic agent. The
CC method generates a population of genetically engineered T cells that
CC persist in a patient for a period of four months to three years after
CC administration. The present sequence is a murine anti-CD19 scFv antibody
CC used for vector construction which is further used to obtain the chimeric
CC antigen receptor of the invention.
XX
SQ Sequence 242 AA;
Query Match 100.0%; Score 1279; Length 242;
Best Local Similarity 100.0%;
Matches 242; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQTTSSLSASLGDRVTISCRASQDISKYLNWYQQKPDGTVKLLIYHTSRLHSGVPS 60
Qy 61 RFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPYTFGGGTKLEITGGGGSGGGGSGGG 120
Qy 121 GSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTY 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSEVKLQESGPGLVAPSQSLSVTCTVSGVSLPDYGVSWIRQPPRKGLEWLGVIWGSETTY 180
Qy 181 YNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTV 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YNSALKSRLTIIKDNSKSQVFLKMNSLQTDDTAIYYCAKHYYYGGSYAMDYWGQGTSVTV 240
Qy 241 SS 242
||
Db 241 SS 242
6. Alignment with the amino acid sequence encoded by SEQ ID NO: 41
RESULT 1
ADL67239
(NOTE: this sequence has 2567 duplicates in the database searched.
See complete list at the end of this report)
ID ADL67239 standard; protein; 112 AA.
XX
AC ADL67239;
XX
DT 20-MAY-2004 (first entry)
XX
DE Human CD3 zeta chain intracellular domain.
XX
KW T cell receptor; TCR; CD3 zeta chain; co-stimulatory signalling region;
KW binding element; immunostimulant; therapy; cancer; human.
XX
OS Homo sapiens.
XX
CC PN US2004043401-A1.
XX
CC PD 04-MAR-2004.
XX
CC PF 28-MAY-2003; 2003US-00448256.
XX
PR 28-MAY-2002; 2002US-0383872P.
XX
CC PA (SLOK ) SLOAN KETTERING INST CANCER RES.
XX
CC PI Sadelain M, Brentjens R, Maher J;
XX
DR WPI; 2004-225696/21.
DR N-PSDB; ADL67228.
XX
CC PT New nucleic acid polymer encoding a chimeric T cell receptor having a
CC PT zeta chain portion, useful for treating disorders where the immune
CC PT response needs to be induced, such as cancer.
XX
CC PS Disclosure; SEQ ID NO 14; 25pp; English.
XX
CC The invention relates to a nucleic acid polymer encoding a chimeric T
CC cell receptor (TCR) which comprises human CD3 zeta chain intracellular
CC domain, a co-stimulatory signalling region and a binding element that
CC specifically interacts with a selected target. The methods and
CC compositions of the invention are useful for treating disorders where the
CC immune response needs to be induced, such as cancer. The present sequence
CC is human CD3 zeta chain intracellular domain.
XX
SQ Sequence 112 AA;
Alignment Scores:
Length: 112
Score: 593.00 Matches: 112
Percent Similarity: 100.0% Conservative: 0
Best Local Similarity: 100.0% Mismatches: 0
Query Match: 95.2% Indels: 0
Gaps: 0
US-17-749-824B-41 (1-339) x ADL67239 (1-112)
Qy 1 AGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ArgValLysPheSerArgSerAlaAspAlaProAlaTyrGlnGlnGlyGlnAsnGlnLeu 20
Qy 61 TATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGGCGTGGC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 TyrAsnGluLeuAsnLeuGlyArgArgGluGluTyrAspValLeuAspLysArgArgGly 40
Qy 121 CGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTACAAT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 41 ArgAspProGluMetGlyGlyLysProArgArgLysAsnProGlnGluGlyLeuTyrAsn 60
Qy 181 GAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAAAGGCGAGCGC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GluLeuGlnLysAspLysMetAlaGluAlaTyrSerGluIleGlyMetLysGlyGluArg 80
Qy 241 CGGAGGGGCAAGGGGCACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 ArgArgGlyLysGlyHisAspGlyLeuTyrGlnGlyLeuSerThrAlaThrLysAspThr 100
Qy 301 TACGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC 336
||||||||||||||||||||||||||||||||||||
Db 101 TyrAspAlaLeuHisMetGlnAlaLeuProProArg 112
8. Alignment with SEQ ID NO: 11
BEJ15812
ID BEJ15812 standard; protein; 241 AA.
XX
AC BEJ15812;
XX
DT 16-NOV-2017 (first entry)
XX
DE Anti-GUCY2C single-chain fragment variable (scFv), SEQ ID 14.
XX
KW GUCY2C protein; Heat stable enterotoxin receptor; cancer; cell therapy;
KW cytostatic; guanylyl cyclase 2C; immune stimulation;
KW single domain antibody; t-lymphocyte; therapeutic.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2017167217-A1.
XX
CC PD 05-OCT-2017.
XX
CC PF 30-MAR-2017; 2017WO-CN078740.
XX
PR 01-APR-2016; 2016US-0317261P.
XX
CC PA (INNO-) INNOVATIVE CELLULAR THERAPEUTICS CO LTD.
XX
CC PI Xiao L, Wu Z, Pu C, Cao Z, Sun H, Bi M;
XX
DR WPI; 2017-68343K/73.
XX
CC PT Pharmaceutical composition for stimulating T cell-mediated immune
CC PT response to cell population expressing antigen and for treating cancer,
CC PT comprises human T cells comprising nucleic acid sequence encoding
CC PT chimeric antigen receptor (CAR).
XX
CC PS Claim 2; SEQ ID NO 14; 62pp; English.
XX
CC The present invention relates to a pharmaceutical composition useful for
CC stimulating T cell-mediated immune response to cell population expressing
CC antigen. The invention further relates to: (1) a method for stimulating a
CC T cell-mediated immune response to a cell population expressing the
CC antigen; and (2) a modified T cell comprising a nucleic acid sequence
CC encoding chimeric antigen receptor (CAR). The invention also relates to a
CC use of CAR modified cells for treating cancer. The present sequence
CC represents an anti-guanylyl cyclase 2C (GUCY2C) single-chain fragment
CC variable (scFv), which is useful for the construction of CAR of the
CC invention.
XX
SQ Sequence 241 AA;
ALIGNMENT:
Query Match 100.0%; Score 1283; Length 241;
Best Local Similarity 100.0%;
Matches 241; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVMTQSPATLSVSPGERATLSCRASQSVSRNLAWYQQKPGQAPRLLIYGASTRATGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVMTQSPATLSVSPGERATLSCRASQSVSRNLAWYQQKPGQAPRLLIYGASTRATGIPA 60
Qy 61 RFSGSGSGTEFTLTIGSLQSEDFAVYYCQQYKTWPRTFGQGTNVEIKGGGGSGGGGSGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTEFTLTIGSLQSEDFAVYYCQQYKTWPRTFGQGTNVEIKGGGGSGGGGSGGG 120
Qy 121 GSQVQLQQWGAGLLKPSETLSLTCAVFGGSFSGYYWSWIRQPPGKGLEWIGEINHRGNTN 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GSQVQLQQWGAGLLKPSETLSLTCAVFGGSFSGYYWSWIRQPPGKGLEWIGEINHRGNTN 180
Qy 181 DNPSLKSRVTISVDTSKNQFALKLSSVTAADTAVYYCARERGYTYGNFDHWGQGTLVTVS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DNPSLKSRVTISVDTSKNQFALKLSSVTAADTAVYYCARERGYTYGNFDHWGQGTLVTVS 240
Qy 241 S 241
|
Db 241 S 241
9. Alignment with SEQ ID NO: 35
RESULT 20
BEJ15819
(NOTE: this sequence has 86 duplicates in the database searched.
See complete list at the end of this report)
ID BEJ15819 standard; protein; 69 AA.
XX
AC BEJ15819;
XX
DT 16-NOV-2017 (first entry)
XX
DE CAR construction related hinge and transmembrane domain, SEQ ID 21.
XX
KW cancer; cell therapy; cytostatic; immune stimulation; t-lymphocyte;
KW therapeutic.
XX
OS Unidentified.
XX
CC PN WO2017167217-A1.
XX
CC PD 05-OCT-2017.
XX
CC PF 30-MAR-2017; 2017WO-CN078740.
XX
PR 01-APR-2016; 2016US-0317261P.
XX
CC PA (INNO-) INNOVATIVE CELLULAR THERAPEUTICS CO LTD.
XX
CC PI Xiao L, Wu Z, Pu C, Cao Z, Sun H, Bi M;
XX
DR WPI; 2017-68343K/73.
XX
CC PT Pharmaceutical composition for stimulating T cell-mediated immune
CC PT response to cell population expressing antigen and for treating cancer,
CC PT comprises human T cells comprising nucleic acid sequence encoding
CC PT chimeric antigen receptor (CAR).
XX
CC PS Disclosure; SEQ ID NO 21; 62pp; English.
XX
CC The present invention relates to a pharmaceutical composition useful for
CC stimulating T cell-mediated immune response to cell population expressing
CC antigen. The invention further relates to: (1) a method for stimulating a
CC T cell-mediated immune response to a cell population expressing the
CC antigen; and (2) a modified T cell comprising a nucleic acid sequence
CC encoding chimeric antigen receptor (CAR). The invention also relates to a
CC use of CAR modified cells for treating cancer. The present sequence
CC represents a hinge and transmembrane domain, which is useful for the
CC construction of CAR of the invention.
XX
SQ Sequence 69 AA;
Query Match 100.0%; Score 256; Length 69;
Best Local Similarity 100.0%;
Matches 47; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIY 47
|||||||||||||||||||||||||||||||||||||||||||||||
Db 4 TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIY 50
10. Alignment with SEQ ID NO: 37
RESULT 1
AZX24809
(NOTE: this sequence has 201 duplicates in the database searched.
See complete list at the end of this report)
ID AZX24809 standard; peptide; 22 AA.
XX
AC AZX24809;
XX
DT 02-AUG-2012 (first entry)
XX
DE Human CD8 transmembrane peptide SEQ ID NO:22.
XX
KW CD8 protein; T-cell surface glycoprotein CD8; cancer; cell therapy;
KW chimeric protein; cytostatic; gene expression; gene therapy;
KW immune stimulation; leukemia; lymphoma; protein therapy; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2012079000-A1.
XX
CC PD 14-JUN-2012.
XX
CC PF 09-DEC-2011; 2011WO-US064191.
XX
PR 09-DEC-2010; 2010US-0421470P.
PR 29-JUN-2011; 2011US-0502649P.
XX
CC PA (UPEN ) UNIV PENNSYLVANIA.
XX
CC PI June CH, Levine BL, Porter DL, Kalos MD;
XX
DR WPI; 2012-G81463/42.
DR N-PSDB; AZX24803.
XX
CC PT New isolated nucleic acid sequence encoding a chimeric antigen receptor
CC PT containing antigen binding domain, transmembrane domain, costimulatory
CC PT signaling region, and zeta signaling domain, useful for treating cancer,
CC PT and lymphocytic leukemia.
XX
CC PS Example 2; SEQ ID NO 22; 131pp; English.
XX
CC The invention relates to a novel isolated nucleic acid sequence encoding
CC a chimeric antigen receptor (CAR) useful for treating cancer, and
CC lymphocytic leukemia selected from refractory CD19+ leukemia and lymphoma
CC in a patient. The CAR of SEQ ID NO: 12 (AZX24799) comprises an antigen
CC binding domain, a transmembrane domain, a costimulatory signaling region,
CC and a CD3 zeta signaling domain of SEQ ID NO: 24 (AZX24811). The
CC invention independently claims for: a cell and a vector comprising a
CC nucleic acid sequence of SEQ ID NO: 8 (AZX24795) encoding the CAR; a
CC method of stimulating a T cell-mediated immune response to a target cell
CC population or tissue in a mammal; a method of providing an anti-tumor
CC immunity in a mammal; a method of treating a mammal having a disease,
CC disorder or condition associated with an elevated expression of a tumor
CC antigen; a method of generating a persisting population of genetically
CC engineered T cells in a patient diagnosed with cancer; and a method of
CC expanding a population of genetically engineered T cells in a patient
CC diagnosed with cancer. The isolated nucleic acid sequence treats a
CC patient who is resistant to at least one chemotherapeutic agent. The
CC method generates a population of genetically engineered T cells that
CC persist in a patient for a period of four months to three years after
CC administration. The present sequence is a human CD8 transmembrane DNA
CC used for vector construction which is further used to obtain the chimeric
CC antigen receptor of the invention.
XX
SQ Sequence 22 AA;
Query Match 100.0%; Score 117; Length 22;
Best Local Similarity 100.0%;
Matches 22; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 IWAPLAGTCGVLLLSLVITLYC 22
||||||||||||||||||||||
Db 1 IWAPLAGTCGVLLLSLVITLYC 22
11. Alignment with SEQ ID NO: 535
RESULT 1
BFE93953
(NOTE: this sequence has 13 duplicates in the database searched.
See complete list at the end of this report)
ID BFE93953 standard; protein; 485 AA.
XX
AC BFE93953;
XX
DT 31-MAY-2018 (first entry)
XX
DE Colorectal cancer treatment related CAR construct, SEQ ID 40.
XX
KW CD3-zeta protein; CD3Z protein; GUCY2C protein; Guanylyl cyclase 2C;
KW Heat stable enterotoxin receptor; T-cell CD3 glycoprotein zeta chain;
KW cancer; cytostatic; fusion protein; immune stimulation; immunotherapy;
KW therapeutic.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN WO2018064921-A1.
XX
CC PD 12-APR-2018.
XX
CC PF 25-AUG-2017; 2017WO-CN098971.
XX
PR 06-OCT-2016; 2016US-0404898P.
XX
CC PA (INNO-) INNOVATIVE CELLULAR THERAPEUTICS CO LTD.
XX
CC PI Xiao L, Wu Z, Pu C, Cao Z, Sun H, Bi M;
XX
DR WPI; 2018-283870/28.
XX
CC PT Isolate nucleic acid sequence encoding chimeric antigen receptor for
CC PT stimulating anti-tumor immune response in patient, comprises antigen
CC PT binding domain that binds to FZD10, thyroid-stimulating hormone and
CC PT prolactin receptor.
XX
CC PS Claim 5; SEQ ID NO 40; 86pp; English.
XX
CC The present invention relates to a novel isolated nucleic acid sequence
CC encoding a chimeric antigen receptor (CAR), useful for treating cancer.
CC The invention further relates to: 1) a vector comprising the isolated
CC nucleic acid sequence; 2) a cell comprising the isolated nucleic acid
CC sequence; 3) a composition comprising a population of T cells comprising
CC the isolated nucleic acid sequence; and 4) a method for stimulating an
CC anti-tumor immune response in a subject. The method and kit of the
CC invention is useful for treating cancer. The present sequence is a CAR
CC construct comprising a signal peptide, an anti-guanylyl cyclase 2C
CC (GUCY2C) single chain antibody, a hinge region, a transmembrane domain, a
CC co-stimulatory domain and a CD3-zeta glycoprotein, useful for treating
CC colorectal cancer.
XX
SQ Sequence 485 AA;
Query Match 100.0%; Score 2577; Length 485;
Best Local Similarity 100.0%;
Matches 485; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MALPVTALLLPLALLLHAARPEIVMTQSPATLSVSPGERATLSCRASQSVSRNLAWYQQK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MALPVTALLLPLALLLHAARPEIVMTQSPATLSVSPGERATLSCRASQSVSRNLAWYQQK 60
Qy 61 PGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTIGSLQSEDFAVYYCQQYKTWPRTFG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTIGSLQSEDFAVYYCQQYKTWPRTFG 120
Qy 121 QGTNVEIKGGGGSGGGGSGGGGSQVQLQQWGAGLLKPSETLSLTCAVFGGSFSGYYWSWI 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QGTNVEIKGGGGSGGGGSGGGGSQVQLQQWGAGLLKPSETLSLTCAVFGGSFSGYYWSWI 180
Qy 181 RQPPGKGLEWIGEINHRGNTNDNPSLKSRVTISVDTSKNQFALKLSSVTAADTAVYYCAR 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 RQPPGKGLEWIGEINHRGNTNDNPSLKSRVTISVDTSKNQFALKLSSVTAADTAVYYCAR 240
Qy 241 ERGYTYGNFDHWGQGTLVTVSSAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAV 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 ERGYTYGNFDHWGQGTLVTVSSAKPTTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAV 300
Qy 301 HTRGLDFACDIYIWAPLAGTCGVLLLSLVITKRGRKKLLYIFKQPFMRPVQTTQEEDGCS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 HTRGLDFACDIYIWAPLAGTCGVLLLSLVITKRGRKKLLYIFKQPFMRPVQTTQEEDGCS 360
Qy 361 CRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGG 420
Qy 421 KPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQ 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 KPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQ 480
Qy 481 ALPPR 485
|||||
Db 481 ALPPR 485
12. Alignment with SEQ ID NO: 332
RESULT 3
AYL46092
(NOTE: this sequence has 22 duplicates in the database searched.
See complete list at the end of this report)
ID AYL46092 standard; DNA; 390 BP.
XX
AC AYL46092;
XX
DT 23-DEC-2010 (first entry)
XX
DE Human nuclear factor of activated T-cells (NFAT) promoter DNA, SEQ: 4.
XX
KW NFAT gene; T-cell transcription factor NFAT; anti-hiv; antiinflammatory;
KW antiparasitic; cancer; cytostatic; dermatological; ds;
KW gastrointestinal-gen.; gene therapy; hepatitis; hepatotropic;
KW herpesvirus infection; hiv infection; influenza virus infection;
KW melanoma; nuclear factor of activated T-cells;
KW plasmodium falciparum infection; promoter; prophylactic to disease;
KW respiratory-gen.; therapeutic; virucide.
XX
OS Homo sapiens.
XX
CC PN WO2010126766-A1.
XX
CC PD 04-NOV-2010.
XX
CC PF 22-APR-2010; 2010WO-US031988.
XX
PR 30-APR-2009; 2009US-0174046P.
XX
CC PA (USSH ) US DEPT HEALTH&HUMAN SERVICES.
XX
CC PI Morgan RA, Rosenberg SA, Zhang L, Restifo NP;
XX
DR WPI; 2010-N79164/75.
XX
CC PT New isolated/purified nucleic acid comprises nucleotide sequence encoding
CC PT nuclear factor of activated T-cells promoter operatively associated with
CC PT nucleotide sequence encoding interleukin-12 for treating e.g. herpes,
CC PT hepatitis and cancer.
XX
CC PS Claim 6; SEQ ID NO 4; 64pp; English.
XX
CC The present invention relates to a novel isolated or purified nucleic
CC acid useful in the treatment or prevention of an infectious disease or
CC cancer in a mammal. The infectious agent can be HIV, influenza, herpes,
CC hepatitis or malaria and the cancer can be a melanoma. The isolated or
CC purified nucleic acid comprises a nucleotide sequence encoding a nuclear
CC factor of activated T-cells (NFAT) promoter operatively associated with a
CC nucleotide sequence encoding interleukin-12 (IL12). The invention further
CC provides recombinant expression vectors, host cells, populations of
CC cells, and pharmaceutical compositions involved in the treatment or
CC prevention of an infectious disease or cancer in a mammal. The nucleic
CC acid is useful in controlling the expression of IL12 to enhance cytolytic
CC activity and eliminating the toxicity of IL12. The present sequence
CC represents a human nuclear factor of activated T-cells (NFAT) promoter of
CC the novel nucleic acid which is useful in controlling the expression of
CC IL12 to enhance cytolytic activity and in the treatment or prevention of
CC an infectious disease or cancer in a mammal as described in the
CC invention.
XX
SQ Sequence 390 BP; 131 A; 75 C; 81 G; 103 T; 0 U; 0 Other;
Query Match 100.0%; Score 277; Length 390;
Best Local Similarity 100.0%;
Matches 277; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TCGAGGTCGACGGTATCGATAAGCTTGATATCGAATTAGGAGGAAAAACTGTTTCATACA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 TCGAGGTCGACGGTATCGATAAGCTTGATATCGAATTAGGAGGAAAAACTGTTTCATACA 60
Qy 61 GAAGGCGTCAATTAGGAGGAAAAACTGTTTCATACAGAAGGCGTCAATTAGGAGGAAAAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GAAGGCGTCAATTAGGAGGAAAAACTGTTTCATACAGAAGGCGTCAATTAGGAGGAAAAA 120
Qy 121 CTGTTTCATACAGAAGGCGTCAATTGGTCCCATCGAATTAGGAGGAAAAACTGTTTCATA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CTGTTTCATACAGAAGGCGTCAATTGGTCCCATCGAATTAGGAGGAAAAACTGTTTCATA 180
Qy 181 CAGAAGGCGTCAATTAGGAGGAAAAACTGTTTCATACAGAAGGCGTCAATTAGGAGGAAA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 CAGAAGGCGTCAATTAGGAGGAAAAACTGTTTCATACAGAAGGCGTCAATTAGGAGGAAA 240
Qy 241 AACTGTTTCATACAGAAGGCGTCAATTGGTCCCGGGA 277
|||||||||||||||||||||||||||||||||||||
Db 241 AACTGTTTCATACAGAAGGCGTCAATTGGTCCCGGGA 277
13. Alignment with SEQ ID NO: 457
RESULT 1
BCB30929
(NOTE: this sequence has 16 duplicates in the database searched.
See complete list at the end of this report)
ID BCB30929 standard; protein; 74 AA.
XX
AC BCB30929;
XX
DT 13-AUG-2015 (first entry)
XX
DE Hypoxia-inducible factor 1-alpha (HIF-1 alpha), SEQ ID:22.
XX
KW HIF-1 alpha protein; Hypoxia inducible factor-1 alpha; cancer;
KW cytostatic; immunotherapy; solid tumor; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2015092024-A2.
XX
CC PD 25-JUN-2015.
XX
CC PF 19-DEC-2014; 2014WO-EP078876.
XX
PR 20-DEC-2013; 2013DK-00070806.
XX
CC PA (CELL-) CELLECTIS.
XX
CC PI Juillerat A, Bertonati C, Valton J, Duchateau P, Poirot L;
XX
DR WPI; 2015-360688/48.
DR GENBANK; Q16665.
XX
CC PT New chimeric antigen receptor useful for engineering immune cell useful
CC PT in therapeutic composition for treating cancer, comprising extracellular
CC PT ligand binding domain, transmembane domain, and oxygen-sensitive
CC PT polypeptide domain.
XX
CC PS Claim 2; SEQ ID NO 22; 102pp; English.
XX
CC The present invention relates to a novel chimeric antigen receptor (CAR)
CC for engineering an immune cell for immunotherapy. The invention further
CC claims: (1) a method for engineering an immune cell for specifically
CC targeting a cell; (3) the immune cell obtained by the method; and (4) a
CC method for treating a subject using the immune cell. The immune cell is
CC useful in therapeutic composition for treating a cancer, preferably solid
CC tumors. The present sequence is a hypoxia-inducible factor 1-alpha (HIF-1
CC alpha), which is useful in the method for engineering an immune cell for
CC immunotherapy.
XX
SQ Sequence 74 AA;
Query Match 100.0%; Score 369; Length 74;
Best Local Similarity 100.0%;
Matches 74; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GIIQHDLIFSLQQTECVLKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GIIQHDLIFSLQQTECVLKPVESSDMKMTQLFTKVESEDTSSLFDKLKKEPDALTLLAPA 60
Qy 61 AGDTIISLDFGSND 74
||||||||||||||
Db 61 AGDTIISLDFGSND 74
14. Alignment with SEQ ID NO: 30
RESULT 1
BAN78353
(NOTE: this sequence has 545 duplicates in the database searched.
See complete list at the end of this report)
ID BAN78353 standard; protein; 69 AA.
XX
AC BAN78353;
XX
DT 20-JUN-2013 (first entry)
XX
DE CD8 transmembrane domain, SEQ 33.
XX
KW T-cell surface glycoprotein CD8; cancer; cytostatic; diagnostic test;
KW prophylactic to disease; recombinant protein; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2013059593-A1.
XX
CC PD 25-APR-2013.
XX
CC PF 19-OCT-2012; 2012WO-US061025.
XX
PR 20-OCT-2011; 2011US-0549516P.
XX
CC PA (USSH ) US DEPT HEALTH&HUMAN SERVICES.
XX
CC PI Orentas RJ, Mackall CL, Pastan IH;
XX
DR WPI; 2013-G24619/30.
XX
CC PT New chimeric antigen receptor comprising an antigen binding domain of
CC PT bacterial 22, a transmembrane domain and an intracellular T cell
CC PT signaling domain, useful for treating or preventing cancer e.g. acute
CC PT lymphocytic cancer.
XX
CC PS Claim 9; SEQ ID NO 33; 55pp; English.
XX
CC The present invention relates to a novel chimeric antigen receptor (CAR),
CC useful for treating or preventing cancer in a mammal. The novel CAR
CC comprises an antigen binding domain of immunotoxin HA22, a transmembrane
CC domain and an intracellular T cell signaling domain, or an antigen
CC binding domain of immunotoxin BL22, a transmembrane domain and an
CC intracellular T cell signaling domain comprising CD28 and/or CD137, where
CC the antigen binding domain can be a light chain variable (VL) region or a
CC heavy chain variable (VH) region. The invention further discloses: (1) a
CC nucleic acid comprising a nucleotide encoding the CAR; (2) a recombinant
CC expression vector comprising the nucleic acid; (3) an isolated host cell
CC comprising the recombinant expression vector; (4) a population of cells
CC comprising the host cell; (5) an antibody, or its antigen binding
CC portion, which specifically binds to the CAR; and (6) a method for
CC detecting, preventing or treating a cancer in a mammal. The composition
CC can be used in conjunction with other therapeutic agents or therapies so
CC as to avoid repeated administrations of the composition thus increasing
CC convenience to the subject and the physician. The present sequence
CC represents a CD8 transmembrane domain present in the novel CAR of the
CC invention.
XX
SQ Sequence 69 AA;
Query Match 100.0%; Score 373; Length 69;
Best Local Similarity 100.0%;
Matches 69; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLL 60
Qy 61 LSLVITLYC 69
|||||||||
Db 61 LSLVITLYC 69
15. Alignment with SEQ ID NO: 287
RESULT 1
AAE15825
(NOTE: this sequence has 407 duplicates in the database searched.
See complete list at the end of this report)
ID AAE15825 standard; protein; 212 AA.
XX
AC AAE15825;
XX
DT 15-JUN-2007 (revised)
DT 26-MAR-2002 (first entry)
XX
DE Human interferon (IFN) beta 2 protein.
XX
KW Human; vaccine; immunostimulatory molecule; interferon; IFN; therapy;
KW antigen presentation; vaccine; tumourigenesis; cancer; cytostatic;
KW antitumour; antibacterial; virucide; fungicide; protozoacide; BOND_PC;
KW interleukin 6 (interferon, beta 2);
KW interleukin 6 (interferon, beta 2) [Homo sapiens]; IL6; HGF; HSF; BSF2;
KW IL-6; IFNB2; interleukin 6 (interferon, beta 2), isoform CRA_a;
KW interleukin 6 (interferon, beta 2), isoform CRA_a [Homo sapiens];
KW unknown; unknown [Homo sapiens]; interleukin-6;
KW interleukin-6 [Homo sapiens]; interferon 6 precursor; interleukin 6;
KW hybridoma growth factor peptide; interleukin 6 [Homo sapiens];
KW unnamed protein product; unnamed protein product [Homo sapiens];
KW put. mature polypeptide (AA 1-184); IL6 [Homo sapiens];
KW B cell stimulatory factor-2 (BSF-2);
KW B cell stimulatory factor-2 (BSF-2) [Homo sapiens];
KW interleukin 6 [synthetic construct];
KW interleukin 6 (interferon, beta 2) [synthetic construct]; GO1781; GO5125;
KW GO5138; GO5515; GO5576; GO5615; GO6953; GO6959; GO7166; GO7267; GO8284;
KW GO8285; GO43066; GO45079; GO45630; GO45727.
XX
OS Homo sapiens.
XX
CC PN WO200188097-A1.
XX
CC PD 22-NOV-2001.
XX
CC PF 17-MAY-2001; 2001WO-AU000565.
XX
PR 17-MAY-2000; 2000AU-00007553.
XX
CC PA (MONU ) UNIV MONASH.
XX
CC PI Ralph SJ;
XX
DR WPI; 2002-082990/11.
DR N-PSDB; AAD25505.
DR PC:NCBI; gi10834984.
DR PC:SWISSPROT; P05231.
DR PC:BIND; 116560, 179493, 116559, 179102, 262686, 227104, 179037.
XX
CC PT New composition, useful for treatment and/or prophylaxis of cancer and
CC PT tumor, comprises immunostimulatory molecule and animal cells cultured in
CC PT presence of interferon to enhance antigen presenting function of the
CC PT cells.
XX
CC PS Claim 40; Page 91; 127pp; English.
XX
CC The present invention relates to a composition of matter comprising an
CC immunostimulatory molecule and animal cells cultured in the presence of
CC at least one interferon (IFN) for a time and under conditions sufficient
CC to enhance the antigen presenting function of the cells. The invention is
CC used as vaccine. The composition is useful for treatment and/or
CC prophylaxis of tumourigenesis, cancer, viral, bacterial, fungal and
CC protozoal infections. The composition which comprises the soluble
CC immunostimulatory molecule and the cultured animal cells is administered
CC separately, sequentially or simultaneously to the patient. The present
CC sequence is human IFN beta 2 protein
CC
CC Revised record issued on 15-JUN-2007 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 212 AA;
Query Match 100.0%; Score 1071; Length 212;
Best Local Similarity 100.0%;
Matches 212; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MNSFSTSAFGPVAFSLGLLLVLPAAFPAPVPPGEDSKDVAAPHRQPLTSSERIDKQIRYI 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MNSFSTSAFGPVAFSLGLLLVLPAAFPAPVPPGEDSKDVAAPHRQPLTSSERIDKQIRYI 60
Qy 61 LDGISALRKETCNKSNMCESSKEALAENNLNLPKMAEKDGCFQSGFNEETCLVKIITGLL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LDGISALRKETCNKSNMCESSKEALAENNLNLPKMAEKDGCFQSGFNEETCLVKIITGLL 120
Qy 121 EFEVYLEYLQNRFESSEEQARAVQMSTKVLIQFLQKKAKNLDAITTPDPTTNASLLTKLQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 EFEVYLEYLQNRFESSEEQARAVQMSTKVLIQFLQKKAKNLDAITTPDPTTNASLLTKLQ 180
Qy 181 AQNQWLQDMTTHLILRSFKEFLQSSLRALRQM 212
||||||||||||||||||||||||||||||||
Db 181 AQNQWLQDMTTHLILRSFKEFLQSSLRALRQM 212
16. Alignment with SEQ ID NO: 328
RESULT 1
AAB99130
(NOTE: this sequence has 273 duplicates in the database searched.
See complete list at the end of this report)
ID AAB99130 standard; protein; 166 AA.
XX
AC AAB99130;
XX
DT 15-JUN-2007 (revised)
DT 29-AUG-2001 (first entry)
XX
DE Human interferon gamma dimer subunit precursor.
XX
KW Human; interferon gamma; cytostatic; antibacterial; virucide; IFNG;
KW antiinflammatory; antirheumatic; antiarthritic; osteopathic; cytokine;
KW interstitial pulmonary disease; idiopathic pulmonary fibrosis;
KW interstitial lung disease; cancer; bacterial infection; viral infection;
KW inflammatory disease; granulomatous disease; bone disorder;
KW malignant osteoporosis; autoimmune disease; rheumatoid arthritis;
KW BOND_PC; interferon, gamma; interferon, gamma [Homo sapiens]; IFNG; IFG;
KW IFI; interferon gamma; interferon gamma [Homo sapiens]; interferon-gamma;
KW interferon-gamma [Homo sapiens]; unnamed protein product;
KW unnamed protein product [Homo sapiens]; GO1558; GO1781; GO5125; GO5133;
KW GO5576; GO5615; GO6925; GO6928; GO7166; GO7267; GO9615; GO19882; GO30593;
KW GO30968; GO31642; GO42742; GO45080; GO45084; GO45348; GO45410; GO45449;
KW GO45893; GO48304; GO50718; GO50776.
XX
OS Homo sapiens.
XX
CC PN WO200136001-A2.
XX
CC PD 25-MAY-2001.
XX
CC PF 13-NOV-2000; 2000WO-DK000631.
XX
PR 12-NOV-1999; 99DK-00001631.
PR 18-NOV-1999; 99US-0166293P.
PR 17-MAR-2000; 2000DK-00000447.
XX
CC PA (MAXY-) MAXYGEN APS.
XX
CC PI Jensen AD, Andersen KV, Hansen CK;
XX
DR WPI; 2001-355555/37.
DR PC:NCBI; gi56786138.
DR PC:SWISSPROT; P01579.
DR PC:BIND; 316097.
XX
CC PT Novel conjugate useful for treating interstitial pulmonary diseases,
CC PT exhibits interferon (IFN) gamma activity and comprises non-polypeptide
CC PT group covalently attached to IFNgamma polypeptide that differs from
CC PT parent IFNgamma.
XX
CC PS Disclosure; Page 62-63; 72pp; English.
XX
CC Interferon gamma (IFNG) is a cytokine produced by T-cells and natural
CC killer cells. IFNG exists as a homodimer of two noncovalently bound
CC polypeptide subunits. The present sequence is the precursor form of human
CC IFNG dimer subunit, which was used in the present invention. The present
CC invention relates to a conjugate exhibiting IFNG activity. The conjugate
CC comprises a first non-polypeptide group covalently attached to an IFNG
CC polypeptide, the polypeptide comprising an amino acid sequence that
CC differs from that of a parent IFNG polypeptide in at least one introduced
CC and/or one removed amino acid residue comprising an attachment group for
CC the non-polypeptide group. The conjugate is useful for the treatment of
CC interstitial pulmonary diseases, preferably idiopathic pulmonary
CC fibrosis, interstitial lung diseases, cancer, bacterial and viral
CC infections, inflammatory diseases, granulomatous diseases, bone disorders
CC such as malignant osteoporosis, and autoimmune diseases such as
CC rheumatoid arthritis
CC
CC Revised record issued on 15-JUN-2007 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 166 AA;
Query Match 100.0%; Score 856; Length 166;
Best Local Similarity 100.0%;
Matches 166; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKYTSYILAFQLCIVLGSLGCYCQDPYVKEAENLKKYFNAGHSDVADNGTLFLGILKNWK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKYTSYILAFQLCIVLGSLGCYCQDPYVKEAENLKKYFNAGHSDVADNGTLFLGILKNWK 60
Qy 61 EESDRKIMQSQIVSFYFKLFKNFKDDQSIQKSVETIKEDMNVKFFNSNKKKRDDFEKLTN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EESDRKIMQSQIVSFYFKLFKNFKDDQSIQKSVETIKEDMNVKFFNSNKKKRDDFEKLTN 120
Qy 121 YSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQMLFRGRRASQ 166
||||||||||||||||||||||||||||||||||||||||||||||
Db 121 YSVTDLNVQRKAIHELIQVMAELSPAAKTGKRKRSQMLFRGRRASQ 166
17. Alignment with SEQ ID NO: 310
RESULT 1
BCB39667
(NOTE: this sequence has 35 duplicates in the database searched.
See complete list at the end of this report)
ID BCB39667 standard; protein; 532 AA.
XX
AC BCB39667;
XX
DT 13-AUG-2015 (first entry)
XX
DE Human single-chain IL-12 fusion protein construct (1480544), SEQ ID 36.
XX
KW IL-12; Interleukin 12 ligand; antimicrobial-gen.; cancer; cytostatic;
KW fusion protein; immune disorder; immune stimulation; immunomodulator;
KW infection; infectious disease; protein therapy; recombinant protein;
KW therapeutic.
XX
OS Homo sapiens.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Region 1..328
FT /note= "Human interleukin-12 p40 subunit protein fragment
FT (1-328)"
FT Region 329..335
FT /note= "Linker"
FT Region 344..532
FT /note= "Human interleukin-12 p35 subunit protein fragment
FT (57-253)"
XX
CC PN WO2015095249-A1.
XX
CC PD 25-JUN-2015.
XX
CC PF 17-DEC-2014; 2014WO-US070695.
XX
PR 18-DEC-2013; 2013US-0917495P.
XX
CC PA (INTR-) INTREXON CORP.
XX
CC PI Zhang C, Sopczynski JM;
XX
DR WPI; 2015-365200/45.
DR N-PSDB; BCB39666.
XX
CC PT New single-chain interleukin (IL)-12 polypeptide comprises first IL-12
CC PT p40 domain (p40N), optional first peptide linker, IL-12 p35 domain,
CC PT optional second peptide linker, and second IL-12 p40 domain (p40C), used
CC PT for treating cancer.
XX
CC PS Example 1; SEQ ID NO 36; 89pp; English.
XX
CC The present invention relates to a novel single-chain interleukin-12 (IL-
CC 12) polypeptide and its applications. The single-chain IL-12 polypeptide
CC comprising from N- to C-terminus: (i) a first IL-12 p40 domain (p40N);
CC (ii) an optional first peptide linker; (iii) an IL-12 p35 domain; (iv) an
CC optional second peptide linker; and (v) a second IL-12 p40 domain (p40C).
CC The first IL-12 p40N is an N-terminal fragment of a p40 subunit; the IL-
CC 12 p35 domain is a mature p35 subunit or its fragment; and the second IL-
CC 12 p40C is a C-terminal fragment of a p40 subunit. The invention also
CC provides: (1) a polynucleotide comprising a nucleic acid sequence
CC encoding the single chain IL-12 polypeptide; (2) a vector comprising the
CC polynucleotide; (3) an isolated host cell or a non-human organism
CC transformed or transfected with the vector; (4) a method for treating a
CC patient comprising administering an amount of the single chain IL-12
CC polypeptide, the polynucleotide, the vector, or the host cell; and (5) a
CC medicament comprising the polypeptide, the polynucleotide, the vector, or
CC the isolated host cell. The single chain IL-12 polypeptide, the
CC polynucleotide, the vector, or the host cell is useful for preparing a
CC medicament for treating a condition selected from cancer, an infectious
CC disease, and an immune system disorder, where cancer is selected from
CC breast cancer, prostate cancer, lymphoma, skin cancer, pancreatic cancer,
CC colon cancer, melanoma, malignant melanoma, ovarian cancer, brain cancer,
CC primary brain carcinoma, head-neck cancer, glioma, glioblastoma, liver
CC cancer, bladder cancer, non-small cell lung cancer, head or neck
CC carcinoma, breast carcinoma, ovarian carcinoma, lung carcinoma, small-
CC cell lung carcinoma, Wilms' tumor, cervical carcinoma, testicular
CC carcinoma, bladder carcinoma, pancreatic carcinoma, stomach carcinoma,
CC colon carcinoma, prostatic carcinoma, genitourinary carcinoma, thyroid
CC carcinoma, esophageal carcinoma, myeloma, multiple myeloma, adrenal
CC carcinoma, renal cell carcinoma, endometrial carcinoma, adrenal cortex
CC carcinoma, malignant pancreatic insulinoma, malignant carcinoid
CC carcinoma, choriocarcinoma, mycosis fungoides, malignant hypercalcemia,
CC cervical hyperplasia, leukemia, acute lymphocytic leukemia, chronic
CC lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous
CC leukemia, chronic granulocytic leukemia, acute granulocytic leukemia,
CC hairy cell leukemia, neuroblastoma, rhabdomyosarcoma, Kaposi's sarcoma,
CC polycythemia vera, essential thrombocytosis, Hodgkin's disease, non-
CC Hodgkin's lymphoma, soft-tissue sarcoma, mesothelioma, osteogenic
CC sarcoma, primary macroglobulinemia, and retinoblastoma. The single chain
CC IL-12 fusion proteins and nucleic acids encoding fusion proteins are
CC provided for use in enhancing immune system function, for example as
CC vaccine adjuvants and in the treatment of infections and cancer. The
CC present sequence is a human single-chain IL-12 fusion protein construct
CC (1480544) comprising human interleukin-12 p40 subunit fragments, human
CC interleukin-12 p35 subunit fragment and a linker peptide, used in the
CC invention for treating a condition selected from cancer, an infectious
CC disease, and an immune system disorder.
XX
SQ Sequence 532 AA;
Query Match 100.0%; Score 2811; Length 532;
Best Local Similarity 100.0%;
Matches 532; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MCHQQLVISWFSLVFLASPLVAIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITW 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MCHQQLVISWFSLVFLASPLVAIWELKKDVYVVELDWYPDAPGEMVVLTCDTPEEDGITW 60
Qy 61 TLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TLDQSSEVLGSGKTLTIQVKEFGDAGQYTCHKGGEVLSHSLLLLHKKEDGIWSTDILKDQ 120
Qy 121 KEPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAATLSAERV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 KEPKNKTFLRCEAKNYSGRFTCWWLTTISTDLTFSVKSSRGSSDPQGVTCGAATLSAERV 180
Qy 181 RGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKN 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 RGDNKEYEYSVECQEDSACPAAEESLPIEVMVDAVHKLKYENYTSSFFIRDIIKPDPPKN 240
Qy 241 LQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVIC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LQLKPLKNSRQVEVSWEYPDTWSTPHSYFSLTFCVQVQGKSKREKKDRVFTDKTSATVIC 300
Qy 301 RKNASISVRAQDRYYSSSWSEWASVPCSGGGGGGSRNLPVATPDPGMFPCLHHSQNLLRA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 RKNASISVRAQDRYYSSSWSEWASVPCSGGGGGGSRNLPVATPDPGMFPCLHHSQNLLRA 360
Qy 361 VSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITN 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 VSNMLQKARQTLEFYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITN 420
Qy 421 GSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELM 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GSCLASRKTSFMMALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELM 480
Qy 481 QALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS 532
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 QALNFNSETVPQKSSLEEPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS 532