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Claims 20 – 23 and 27 – 34 were pending, with claim 21, 28, and 42, directed to non-elected species withdrawn. Claims 20 and 32 – 33 have been amended. Claim 27 has been canceled. Claims 35 – 42 have been newly added. Claims 20, 22 – 23, and 29 – 34 are the subject of this Office Action.
WITHDRAWN REJECTIONS
Claim Rejections - 35 USC § 103
Claims 20, 22 – 23, 27, ad 29 – 34 were rejected under 35 U.S.C. 103 as being unpatentable over CRANE (WO 2017/ A1, published 03/16/2017; see PTO-892: Notice of References Cited of 08/01/2024) 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 08/01/2024), SLAWIN (WO 2011/130566 A2, published 10/20/2011; see PTO-892 of 08/01/2024), JENSEN (WO 2001/036001 A2, published 05/25/2001; see PTO-892 of 08/01/2024; see PTO-892 of 08/01/2024), and ANDERSON (Anderson, KG et al. “Obstacles Posed by the Tumor Microenvironment to T Cell Activity: A Case for Synergistic Therapies.” Cancer cell 31.3 (2017): 311–325; see PTO-892 of 08/01/2024).
In view of the claim amendments in the reply of 12/16/2025, this rejection is withdrawn.
Double Patenting
Claims 20, 22, 23, 27, 29 – 34 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 10, 13, 17, 18, and 20 of U.S. Patent No. 10,918,667 in view of CRANE, OLADAPO, SLAWIN, JENSEN, and ANDERSON.
In view of the claim amendments in the reply of 12/16/2025, this rejection is withdrawn.
Claims 20, 22, 23, 27, 29 – 34 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims listed in the table below of U.S. Patent No. listed in the table below in view of CRANE, OLADAPO, SLAWIN, JENSEN, and ANDERSON.
U.S. Patent No.
Claim No(s).
1
11,104,732
1 and 3 – 12
2
11,788,072
1, 6, and 8 - 18
3
11,932,700
1 – 8
In view of the claim amendments in the reply of 12/16/2025, this rejection is withdrawn.
Claims 20, 22, 23, 27, 29 – 34 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims listed in the table below of copending Application No. listed in the table below in view of CRANE, OLADAPO, SLAWIN, JENSEN, and ANDERSON.
U.S. Application No.
Claim No(s).
1
17/091,741
1 – 6, 8 – 12, and 14 - 20
2
17/123,732
1 – 16, 25, and 26
3
17/173,504
1, 10 – 16, and 19 – 21
4
17/420,066
1, 2, 5 – 7, 9 – 18, 21 – 24
5
17/749,824
1 – 23
6
17/996,589
1, 5 – 10, 12, 14, 15, 19, and 20
7
17/998,127
1, 18 – 23
8
18/156,482
1 and 9 – 16
9
18/439,435
1, 7 – 11, 13, and 16
10
18/540,269
1, 7 – 11, 13 – 16, and 21
11
18/563,764
14, 17 – 19, and 23 – 26
12
18/571,062
1, 20 – 22, 25
13
16/856,808
1, 7 – 12, and 18 – 25
In view of the claim amendments in the reply of 12/16/2025, this rejection is withdrawn. Furthermore, in view of the later filing dates of application numbers 17/091,741, 17/123,732, 17/173,504, 17/996,589, 17/998,127, 18/156,482, 18/540,269, 18/563,764, 18/571,062 and 16/856,808, the rejections of the present claims in view of the later-filed applications are withdrawn.
NEW REJECTIONS (necessitated by claim amendments)
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 38 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 38 recites that “the composition comprises modified T cells comprising a CAR that binds GCC.” However, neither the claims nor the specification define(s) “GCC” and thus the scope of the claim is not clear.
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.
Claims 20, 22 – 23, 29 – 36 and 40 – 41 are rejected under 35 U.S.C. 103 as being unpatentable over OLADAPO in view of SLAWIN, JENSEN and SADELAIN (WO 2017/180989 A2, published 10/19/2017).
The present application is directed to a pharmaceutical composition for treating a solid tumor, the composition comprising modified T cells, wherein the modified T cells comprise a chimeric antigen receptor (CAR) and one or more exogenous polynucleotide encoding one or more proteins, the one or more proteins comprising IFNγ, wherein the one or more exogenous polynucleotides comprise a first exogenous polynucleotide encoding SEQ ID NO: 287 (an interleukin-6 (IL-6) amino acid sequence) and a second exogenous polynucleotide encoding SEQ ID NO: 328 (an interferon gamma (IFNγ) amino acid sequence, and wherein expression and/or secretion of each of SEQ ID NO: 287 and SEQ ID NO: 328 is modulated by one or more transcription factors selected from the group consisting of HiF1a, NFAT, FOXP3, NFkB, STAT, AP-1, and a combination thereof.
OLADAPO is directed the significance of cytokines, such as IL-12, to the efficacy of CAR T cells in the treatment of tumors. OLADAPO is directed to optimized CAR T-cells (armored CAR T-cells), where modified second-generation CAR T-cells have been further optimized to inducibly or constitutively secrete active cytokines or express ligands that further armor CAR T-cells to improve efficacy and persistence. OLADAPO teaches that IFNγ improves CAR T-cell cytotoxic function (see p. 413, right column). Thus, OLADAPO teaches that armored CAR T-cells are more effective at treating tumors, rendering the pharmaceutical composition of CAR T cells armored with cytokines IL-6 and IFNγ of present claim 20 obvious.
However, OLADAPO does not teach the specific sequences of SEQ ID NO: 287 and 328. Furthermore, although OLADAPO teaches that the CAR T cells are optimized to inducibly secrete active cytokines, OLADAPO does not teach the modulation of the cytokines with the transcription factors listed in present claim 20.
SLAWIN is directed to methods for treating a solid tumor in a subject in need thereof by activating an immune response against a tumor antigen. See Abstract. SLAWIN discloses that IL-6 is important in T cell priming. See p. 51, lines 4 – 7. The protein sequence for IL-6 is disclosed in SLAWIN’s SEQ ID NO: 14 which is identical to SEQ ID NO: 287 of present claim 20. See Appendix.
JENSEN is directed to a conjugate exhibiting interferon gamma activity that may be used for treatment of various diseases. See Abstract. JENSEN discloses that one of these diseases is cancer. See p. 4, lines 22 – 26. JENSEN’s SEQ ID NO: 1 on p. 62 – 63 is identical to SEQ ID NO: 328 of present claim 25.
SADELAIN is directed to a T cell wherein one or more therapeutic transgenes is integrated at a within the genome of the cell such that expression of the transgene is under control of an endogenous promoter of the T cell. SADELAIN teaches that the transgene encodes a molecule selected from the group consisting of a CAR, a CCR, a cytokine, . . . (see paragraph 0024). SADELAIN teaches that the expression of a transgene is under the control of an endogenous inducible promoter induced by HIF1 alpha transcription factor (see paragraph 00302). In addition, SADELAIN lists other inducers such as NFAT, AP1, and NFκb (see Table 1, between paragraphs 00232 and 00234). SADELAIN teaches that the T cells expressing a CAR is used in a method treating a solid tumor (see paragraphs 00315 – 00316).
Because OLADAPO discloses the significance of IL-6 and IFNγ to the activation of T cells in the success of CAR-T cell therapy in solid tumors, SLAWIN discloses the sequence of IL-6 (present SEQ ID NO: 287), JENSEN discloses the sequence of IFNγ (present SEQ ID NO: 328), and SADELAIN teaches that the expression of cytokines by T cells expressing CARs can be modulated by HIF1a, NFAT, NFκB or AP1, it would have been obvious to one having ordinary skill in the art to combine the teachings of the cited references to arrive to the pharmaceutical composition for treating a solid tumor of claim 20. There would have been a reasonable expectation of success considering that the armoring CAR T cells with cytokines have been known to be effective in treating solid tumors and considering that inducible expression of cytokines are known to be an effective in controlling protein expression, as evidenced by the applied art.
Regarding claim 22, SADELAIN teaches that the inducible promoter is HIF1 alpha, involved in the metabolic response to hypoxia. Furthermore, SADELAIN teaches that the endogenous inducible promoter is induced by a metabolic change (see paragraph 00243). This refers to the metabolic state of the cells. For example, when naive T cells rely on oxidative phosphorylation to generate energy, and when they became activated and differentiate into effector T cell, they switch to glycolysis to generate energy. Hypoxia and low-pH also induce metabolic changes (see paragraph 00249).
Regarding claim 23, SADELAIN teaches the use of inducible promoters within viral vectors (see paragraph 0009).
Regarding claim 29, OLADAPO teaches modifying CAR T-cells to secrete IL-12 as a mechanism to deliver IL-12 to the tumour microenvironment (see p. 413, right column).
Regarding claim 30, SADELAIN teaches that the endogenous promoter that is inducible is induced by activation of the T cell (see paragraph 0017).
Regarding claim 31, SADELAIN teaches that a CAR generally has the structure of a cell surface receptor, with the antigen binding activity, such as an scFv, as at least a portion of the extracellular domain, fused to a transmembrane domain, which is fused to an intracellular domain that has cell signaling activity in a T cell. (see paragraph 00263).
Regarding claim 32, OLADAPO discloses CAR T-cells directed against CD19 (Applicant’s elected species). See p. 413, left column, first paragraph.
Regarding claim 33, OLADAPO discloses second generation CAR T-cell therapy utilizing 4-1BB (Applicant’s elected species) and ‘third generation’ CAR T-cells which utilize two distinct costimulatory domains (e.g. CD28/4-1BB/CD3ζ or CD28/OX-40/CD3ζ). See p. 413, left column, end of first paragraph.
Regarding claims 34 and 35, SADELAIN teaches a method of treating a subject with T cell therapy in need thereof, comprising administering to the subject the pharmaceutical composition of T cell with the disclosed transgene (see claims 1, 8 – 9, and 16 of SADELAIN).
Regarding claim 36, OLADAPO teaches CAR T-cells that were efficacious against cluster of differentiation (CD)19-expressing B-cell malignancies (see abstract).
Regarding claim 40, OLADAPO teaches the modification of T-cells to secrete IL-12 (see p. 413, right column).
Regarding claim 41, SADELAIN teaches inducer NFAT (see Table 1, between paragraphs 00232 and 00234).
Claims 37 and 39 are rejected under 35 U.S.C. 103 as being unpatentable over OLADAPO in view of SLAWIN, JENSEN and SADELAIN as applied to claims 20, 22 – 23, 29 – 36 and 40 – 41 above, and further in view of XIAO (US 20190216851 A1, filed 09/28/2018, published 07/18/2019; see PTO-892).
The teachings of OLADAPO, SLAWIN, JENSEN and SADELAIN are discussed above and fully incorporated herein. However, none of OLADAPO, SLAWIN, JENSEN or SADELAIN teaches a CAR binding TSHR (of present claim 37) or ACPP (of present claim 39).
XIAO is directed to compositions and methods for enhancing T cell response and/or CAR cell expansion in vivo and/or in vitro. XIAO teaches treating solid tumor antigens TSHR and ACPP by administering CAR T cells (see claims 1 and 2 of XIAO).
Because OLADAPO discloses the significance of IL-6 and IFNγ to the success of CAR-T cell therapy in solid tumors, SLAWIN discloses the sequence of IL-6 (present SEQ ID NO: 287), JENSEN discloses the sequence of IFNγ (present SEQ ID NO: 328), SADELAIN teaches that the expression of cytokines by T cells expressing CARs can be modulated by HIF1a, NFAT, NFκB or AP1, and XIAO teaches the effective treatment of solid tumors with CARs targeting antigen TSHR or ACPP, it would have been obvious to one having ordinary skill in the art to combine the teachings of the applied prior art to arrive to the pharmaceutical compositions of claims 37 and 39. There would have been a reasonable expectation of success considering that the therapy involving the combination of CAR-T cells and cytokines are known to be effective in the treatment of solid tumors, as evidenced by the applied art.
Response to Arguments
On page 10 of the reply of 12/16/2025, second paragraph, Applicant argues that “Anderson does not teach or suggest using HIF-1a to control or modulate the expression of exogenous cytokines for treating solid tumors. Similar to Anderson, the other cited references also do not teach or suggest treating solid tumors using CAR and an exogenous polynucleotide encoding one or more cytokines such as IFNγ and IL-6, wherein expression and/or secretion of the one or more cytokines is regulated by one or more transcription factors”.
Applicant’s arguments are not persuasive because ANDERSON teaches “[i]n tumors, oncogenic signaling and hypoxia can drive the expression of glucose metabolism genes”, and thus it would have been obvious to use a promoter that responds to hypoxia to drive the claimed polynucleotides encoding cytokines. Nonetheless, because of further amendments of the claims, ANDERSON is replaced with SADELAIN, a reference that renders the modulation of cytokine expression obvious as discussed above.
On page 11, second paragraph, Applicant argues that “during the video conference interview of November 6, 2025, the Examiners suggested amending the claims to provide structural features for controlling or regulating the expression of the exogenous cytokines and/or secretion to overcome the obviousness rejection”.
Applicant’s argument is not persuasive because, as stated during the interview, a new search must be completed to address any new amendments. After a thorough search of the prior art, new 103 rejections are applied above.
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.
Claims 20, 22 – 23, 27, and 29 – 34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 10, 13, 17, 18, and 20 of U.S. Patent No. 10,918,667 in view of OLADAPO, SLAWIN, JENSEN, SADELAIN and XIAO.
The patented claims recite a pharmaceutical composition, wherein the pharmaceutical composition comprises modified T cells comprising a first nucleic acid encoding a chimeric antigen receptor (CAR) and a second nucleic acid encoding therapeutic agents IL-6 and IFN-γ and comprising SEQ ID NO: 469.
The main difference between the present claims and the patented claims is that the present claims recite that the exogenous polynucleotide comprises SEQ ID NO: 287 and a polynucleotide encoding SEQ ID NO: 328 whose expressions and/or secretion of each of is modulated by a transcription factor listed. However, the cited references disclose this difference. The teachings of the cited references and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the patented claims recite a pharmaceutical composition, wherein the pharmaceutical composition comprises modified T cells comprising a first nucleic acid encoding a chimeric antigen receptor (CAR) and a second nucleic acid encoding therapeutic agents IL-6 and IFN-γ, and the cited references disclose the sequences of IL-6 and IFN-γ, respectively and thus disclose present SEQ ID NOs 297 and 328, respectively, wherein expression and/or secretion of each of SEQ ID NO: 287 and SEQ ID NO:328 is modulated by a transcription modulator, it would have been obvious to one having ordinary skill in the art to use the sequences rendered obvious by the cited references in the pharmaceutical composition of the patented claims to arrive to the present claims.
Claims 20, 22 – 23, 27, and 29 – 34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims listed in the table below of U.S. Patent No. listed in the table below in view of OLADAPO, SLAWIN, JENSEN, SADELAIN and XIAO.
Similar double patenting issues as described in the rejection above were found in other patented claims listed in the table below in view of OLADAPO, SLAWIN, JENSEN, SADELAIN and XIAO render the present claims obvious.
U.S. Patent No.
Claim No(s).
1
11,104,732
1 and 3 – 12
2
11,788,072
1, 6, and 8 - 18
3
11,932,700
1 – 8
Claims 20, 22 – 23, 27, and 29 – 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5 – 8 and 24 – 54 of copending Application No. 17/749,824 in view of OLADAPO, SLAWIN, JENSEN, SADELAIN and XIAO.
Copending claim 1 recites 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; anda fourth vector comprising a polynucleotide encoding second CAR and a polynucleotide encoding IFNy, and wherein the expression and/or secretion of each of IL-6, IL-12, and IFNy is regulated by one or more transcription modulators, optionally wherein the one or more transcription modulators are selected from the group consisting of Hif- la, NFAT, FOXP3, and NFkB.
The main difference between the present claims and the patented claims is that the present claims recite that the exogenous polynucleotide comprises SEQ ID NO: 287 and a polynucleotide encoding SEQ ID NO: 328. However, the cited references disclose this difference. The teachings of the cited references and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the copending claims recite a composition for transfecting or transducing T cells comprising vectors encoding CARs and encoding IL-6 and IFN-γ whose expression is modulated by the transcription factors listed and the cited references disclose the sequences of IL-6 and IFN-γ, it would have been obvious to one having ordinary skill in the art to use the sequences rendered obvious by the cited references in the composition of the copending claims to arrive to the present claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
On page 12 of the reply of 12/16/2025, Applicant argues that the claims of the present application is distinct from those of the cited U.S. patents. However, as discussed above, the secondary references in addition to the U.S. patents render the present claims obvious.
Furthermore, in view of the later filing dates of application numbers 17/091,741, 17/123,732, 17/173,504, 17/996,589, 17/998,127, 18/156,482, 18/540,269, 18/563,764, 18/571,062 and 16/856,808, the rejections of the present claims in view of the later-filed applications are withdrawn.
Conclusion
Claims 20, 22 – 23 and 29 – 41 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Estella Gustilo whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:30 AM - 5:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached at 571-272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
APPENDIX
Alignment with SEQ ID NO: 287
AZN80196
ID AZN80196 standard; protein; 212 AA.
XX
AC AZN80196;
XX
DT 08-DEC-2011 (first entry)
XX
DE Human interleukin-6 (IL-6), SEQ ID 14.
XX
KW IL-6; angiogenesis inhibition; bone tumor; cytostatic;
KW immune stimulation; interleukin 6; liver tumor; lung tumor;
KW prophylactic to disease; prostate tumor; protein therapy; therapeutic;
KW tumor-associated antigen; vaccine, anticancer; BOND_PC;
KW interleukin 6 (interferon, beta 2); IL6; HGF; HSF; BSF2; IL-6; IFNB2;
KW interleukin 6 precursor; hybridoma growth factor; interleukin BSF-2;
KW B-cell differentiation factor; B cell stimulatory factor-2;
KW CTL differentiation factor; interleukin 6;
KW interleukin 6 (interferon, beta 2), isoform CRA_a; unknown;
KW interleukin-6; interferon 6 precursor; hybridoma growth factor peptide;
KW unnamed protein product; put. mature polypeptide (AA 1-184);
KW B cell stimulatory factor-2 (BSF-2); GO1781; GO5125; GO5138; GO5515;
KW GO5576; GO5615; GO6953; GO6959; GO7166; GO7267; GO8284; GO8285; GO43066;
KW GO45079; GO45630; GO45727.
XX
OS Homo sapiens.
XX
CC PN WO2011130566-A2.
XX
CC PD 20-OCT-2011.
XX
CC PF 14-APR-2011; 2011WO-US032572.
XX
PR 16-APR-2010; 2010US-0325127P.
PR 04-JUN-2010; 2010US-0351760P.
PR 14-FEB-2011; 2011US-0442582P.
XX
CC PA (BELL-) BELLICUM PHARM INC.
XX
CC PI Slawin K, Spencer D, Lapteva N;
XX
DR WPI; 2011-N10423/72.
DR N-PSDB; AZN80195.
DR PC:NCBI; gi10834984.
DR PC:SWISSPROT; P05231.
DR PC:BIND; 116560, 179493, 116559, 179102, 262686, 227104, 179037.
XX
CC PT Inducing immune response against tumor antigen involves administering
CC PT cell encoding chimeric protein of membrane targeting region, ligand
CC PT binding region and cluster of differentiation 40 lacking extracellular
CC PT domain, and antigen; and ligand.
XX
CC PS Example 10; SEQ ID NO 14; 267pp; English.
XX
CC The present invention relates to a novel method for treating a solid
CC tumor in a subject. The method involves: administering a transduced or
CC transfected antigen presenting cell to the subject, where the antigen
CC presenting cell is transduced or transfected with a nucleic acid encoding
CC a chimeric protein comprising a membrane targeting region, a multimeric
CC ligand binding region and a CD40 cytoplasmic polypeptide region lacking
CC CD40 extracellular domain; and administering a multimeric ligand that
CC binds to the multimeric ligand binding region. The present invention also
CC provides: a method for inducing an immune response against a tumor
CC antigen in a subject; a method for reducing tumor size, inhibiting tumor
CC growth, reducing or inhibiting tumor vascularization in a subject; a
CC method for preventing prostate cancer in the subject; a method for
CC improving quality of life in the subject; and a method for increasing the
CC chemo-sensitivity of the tumor. The method for treating the solid tumor
CC is useful for treating and preventing tumor in liver, prostate, bone,
CC lymph node and lungs. The antigen presenting cells such as dendritic
CC cells can be used in preparing vaccine against cancer cells. The present
CC sequence is a human interleukin-6 (IL-6), which is used in the
CC exemplification as a biomarker for optimizing the therapeutic methods for
CC treating the solid tumors of the invention.
CC
CC Revised record issued on 22-NOV-2011 : Enhanced with precomputed
CC information from BOND.
XX
SQ Sequence 212 AA;
ALIGNMENT:
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
Alignment with SEQ ID NO: 328
RESULT 1
AAB99130
(NOTE: this sequence has 223 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
Prosecution Insights