DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Preliminary Amendment
The preliminary amendment dated 02/15/2022 has been entered. Claims 1-17 and 29 are pending and under examination.
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. The earliest possible effective filing date for the instant claims is August 19, 2019 based on the filing date of the foreign application EP19192299.6
Election/Restriction
Applicant’s election without traverse of Group I in the reply filed on 07/02/2025 is acknowledged.
Claims 18-20, 22-28, 36-38, 39-41, 43-46 and 48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, generic claims are 1, 18, 36 and 39.
Claims 1-17 and 29 are under examination for their full scope.
Applicant’s species election in the reply filed on 07/02/2025 is acknowledged. Applicant elected SEQ ID NO: 2 as a species of the IRP2 protein, and a T cell as a species of a lymphocyte
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4 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 4 recites the limitation ”modified T cell”. It is unclear the extend of the modifications included in the limitation and therefore, this claim is indefinite.
Appropriate correction is required.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends (claim 3). Claim 4 is drawn to the lymphocyte according to claim 3, wherein the lymphocyte is a tumor infiltrating lymphocyte, a modified T cell or a virus specific T cell and claim 3 is drawn to the lymphocyte, wherein the lymphocyte is a T cell or a natural killer (NK) cell. Claim 4 recites a “tumor infiltrating lymphocyte” which according to the specification: the tumor infiltrating lymphocyte includes T cells and B cells (page 13, 4th paragraph). However, claim 3 does not include B cells. Therefore claim 4 fails to further limit claim 3. For the purposes of compact prosecution, the term ““tumor infiltrating lymphocyte” has been interpreted as “tumor infiltrating T cell” subpopulation of the “tumor infiltrating lymphocyte” population, that is, an activated T cell.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary.
Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-7 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Cullen (US 2019/0100761 A1, Cullen, published on April 4, 2019), in view of Barrett (WO 2017/180587 A2 Barrett, prior filing date: April 1, 2017-04-11), Qin (PLoS ONE May 2010 | Volume 5 | Issue 5, 1-4) and Daniels (Clinical Immunology (2006) 121, 144-158).
Cullen teaches that recombinant DNA technology involves the cloning of a gene encoding a desired polypeptide into a suitable expression vector. The expression vector encoding the desired polypeptide is then transfected into a host cell, which is cultured to produce the RNA encoding the polypeptide. The RNA is translated to produce the polypeptide [0005] (instant claim 1). Cullen also teaches “suitable cells": such as eukaryotic cells (including animal cells and human cells) ……. including a T cell such as a CD4 T cell [0058] (instant claim 3-4) and that promoters useful in the practice of the invention include, but are not limited to, constitutive promoters [0052] (instant claims 1, 5-6).
Cullen does not teach that the desired polypeptide is IRP-2 as set forth in SEQ ID NO: 2, or that the constitutive promoter is EF-1alpha and does not teach pharmaceutical compositions.
Barrett teaches a pharmaceutical composition comprising suitable carriers and excipients (page 2788, [0336]) (instant claim 29). Barrett also teaches the IRP-2 protein encoded by the gene IREB2 which is 100% identical to SEQ ID NO: 2 (instant claims 1 and 2). See sequence alignment below:
Title: US-17-635-534-2
Sequence: 1 MDAPKAGYAFEYLIETLNDS..........VEITLYKHGGLLNFVARKFS 963
US-16-092-829B-42035
Sequence 42035, US/16092829B
Publication No. US20190192691A1
GENERAL INFORMATION
APPLICANT: BARRETT, PETER
APPLICANT: GLADSTONE, MICHAEL N.
APPLICANT: KASSUM, TARIQ A.
APPLICANT: SURI, VIPIN
APPLICANT: LI, DAN JUN
APPLICANT: SUN, DEXUE
APPLICANT: DOLINSKI, BRIAN
TITLE OF INVENTION: REGULATED BIOCIRCUIT SYSTEMS
FILE REFERENCE: 2095.1300US371
CURRENT APPLICATION NUMBER: US/16/092,829B
CURRENT FILING DATE: 2018-10-11
PRIOR APPLICATION NUMBER: PCT/US2017/026950
PRIOR FILING DATE: 2017-04-11
PRIOR APPLICATION NUMBER: 62/320,864
PRIOR FILING DATE: 2016-04-11
PRIOR APPLICATION NUMBER: 62/466,596
PRIOR FILING DATE: 2017-03-03
NUMBER OF SEQ ID NOS: 213456
SEQ ID NO 42035
LENGTH: 963
TYPE: PRT
ORGANISM: Homo sapiens
FEATURE:
OTHER INFORMATION: Payload ID: 8547
FEATURE:
OTHER INFORMATION: Gene Symbol: IREB2
FEATURE:
OTHER INFORMATION: Gene Name:
iron-responsive element binding protein 2
FEATURE:
OTHER INFORMATION: ENSP ID: ENSP00000258886
Query Match 100.0%; Score 5004; Length 963;
Best Local Similarity 100.0%;
Matches 963; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MDAPKAGYAFEYLIETLNDSSHKKFFDVSKLGTKYDVLPYSIRVLLEAAVRNCDGFLMKK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MDAPKAGYAFEYLIETLNDSSHKKFFDVSKLGTKYDVLPYSIRVLLEAAVRNCDGFLMKK 60
Qy 61 EDVMNILDWKTKQSNVEVPFFPARVLLQDFTGIPAMVDFAAMREAVKTLGGDPEKVHPAC
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EDVMNILDWKTKQSNVEVPFFPARVLLQDFTGIPAMVDFAAMREAVKTLGGDPEKVHPAC
Qy 121 PTDLTVDHSLQIDFSKCAIQNAPNPGGGDLQKAGKLSPLKVQPKKLPCRGQTTCRGSCDS
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PTDLTVDHSLQIDFSKCAIQNAPNPGGGDLQKAGKLSPLKVQPKKLPCRGQTTCRGSCDS
Qy 181 GELGRNSGTFSSQIENTPILCPFHLQPVPEPETVLKNQEVEFGRNRERLQFFKWSSRVFK
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GELGRNSGTFSSQIENTPILCPFHLQPVPEPETVLKNQEVEFGRNRERLQFFKWSSRVFK
Qy 241 NVAVIPPGTGMAHQINLEYLSRVVFEEKDLLFPDSVVGTDSHITMVNGLGILGWGVGGIE
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 NVAVIPPGTGMAHQINLEYLSRVVFEEKDLLFPDSVVGTDSHITMVNGLGILGWGVGGIE
Qy 301 TEAVMLGLPVSLTLPEVVGCELTGSSNPFVTSIDVVLGITKHLRQVGVAGKFVEFFGSGV
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TEAVMLGLPVSLTLPEVVGCELTGSSNPFVTSIDVVLGITKHLRQVGVAGKFVEFFGSGV
Qy 361 SQLSIVDRTTIANMCPEYGAILSFFPVDNVTLKHLEHTGFSKAKLESMETYLKAVKLFRN
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 SQLSIVDRTTIANMCPEYGAILSFFPVDNVTLKHLEHTGFSKAKLESMETYLKAVKLFRN
Qy 421 DQNSSGEPEYSQVIQINLNSIVPSVSGPKRPQDRVAVTDMKSDFQACLNEKVGFKGFQIA
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 DQNSSGEPEYSQVIQINLNSIVPSVSGPKRPQDRVAVTDMKSDFQACLNEKVGFKGFQIA
Qy 481 AEKQKDIVSIHYEGSEYKLSHGSVVIAAVISCTNNCNPSVMLAAGLLAKKAVEAGLRVKP
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 AEKQKDIVSIHYEGSEYKLSHGSVVIAAVISCTNNCNPSVMLAAGLLAKKAVEAGLRVKP
Qy 541 YIRTSLSPGSGMVTHYLSSSGVLPYLSKLGFEIVGYGCSICVGNTAPLSDAVLNAVKQGD
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 YIRTSLSPGSGMVTHYLSSSGVLPYLSKLGFEIVGYGCSICVGNTAPLSDAVLNAVKQGD
Qy 601 LVTCGILSGNKNFEGRLCDCVRANYLASPPLVVAYAIA GTVNIDFQTEPLGTDPTGKNIY
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 LVTCGILSGNKNFEGRLCDCVRANYLASPPLVVAYAIA GTVNIDFQTEPLGTDPTGKNIY
Qy 661 LHDIWPSREEVHRVEEEHVILSMFKALKDKIEMGNKRWNSLEAPDSVLFPWDLKSTYIRC
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 LHDIWPSREEVHRVEEEHVILSMFKALKDKIEMGNKRWNSLEAPDSVLFPWDLKSTYIRC
Qy 721 PSFFDKLTKEPIALQAIENAHVLLYLGDSVTTDHISPAGSIARNSAAAKYLTNRGLTPRE
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 PSFFDKLTKEPIALQAIENAHVLLYLGDSVTTDHISPAGSIARNSAAAKYLTNRGLTPRE
Qy 781 FNSYGARRGNDAVMTRGTFANIKLFNKFIGKPAPKTIHFPSGQTLDVFEAAELYQKEGIP
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 FNSYGARRGNDAVMTRGTFANIKLFNKFIGKPAPKTIHFPSGQTLDVFEAAELYQKEGIP
Qy 841 LIILAGKKYGSGNSRDWAAKGPYLLGVKAVLAESYEKIHKDHLIGIGIAPLQFLPGENAD
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 LIILAGKKYGSGNSRDWAAKGPYLLGVKAVLAESYEKIHKDHLIGIGIAPLQFLPGENAD 900
Qy 901 SLGLSGRETFSLTFPEELSPGITLNIQTSTGKVFSVIASFEDDVEITLYKHGGLLNFVAR
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 SLGLSGRETFSLTFPEELSPGITLNIQTSTGKVFSVIASFEDDVEITLYKHGGLLNFVAR
Qy 961 KFS 963
|||
Db 961 KFS 963
Qin teaches that the human elongation factor 1 alpha promoter (EF1A) is a constitutive promoter (abstract) (instant claim 7) and is consistently strong in most cell types (page 1, Results and discussion section).
Daniels teaches that IRP-2 regulates the expression of CD71 (TfR, Transferrin receptor) (page 145, last paragraph). CD71 is ubiquitously expressed at low levels on normal cells and is expressed at greater levels on cells with a high proliferation rate (page 146 first column, second paragraph). In addition, CD71 plays an immunoregulatory role in T cell activation and can provide the second stimulus required for the activation of T cells (page 149, first column, second paragraph) (instant claim 4). Antibodies against CD71 leads to the downregulation of CD71 on the surface of the cells and inhibits the proliferation of mitogen activated T cells (page 152, second column, first paragraph).
It would be obvious to one of ordinary skill in the art to combine the teachings of Cullen, Barrett and Qin to select a lymphocyte or an activated T cell as the cell type to (over)express (1) a synthetic IRP-2 and/or (2) a modified T cell receptor (TCR) (instant claim 4) polynucleotide sequences (genes) to arrive at the claimed invention. It would further be obvious to link the IRP-2 polynucleotide sequence to a constitutive promoter such as EF-1alpha so the gene would be always turned on and thus overexpressing the protein. One of ordinary skill would have been motivated to do so because IRP-2 is involved in cellular iron homeostasis and the regulation of CD71 gene expression. When IRP-2 is overexpressed, there would be an upregulation of CD71 leading to the proliferation of the lymphocyte or activated T cell (as taught by Daniels). There would be a reasonable expectation of success because the recombinant DNA technology taught by Cullen is well known in the art and it is routinely practiced in many molecular biology laboratories in the world.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 8-17 are rejected under 35 U.S.C. 103 as being unpatentable over Cullen, Barrett and Daniels in view of Zhang (Biomarker Research (2017) 5:22. 1-6) and Liu (Sci Rep 7, 2193 (2017) pages 1-9)
Cullen, Barrett and Daniels teachings have been discussed above.
Cullen, Barrett and Daniels do not teach the lymphocyte further comprising a Chimeric antigen receptors (CAR) or the CAR transcriptionally linked to IRP-2 by a sequenced encoding a self-cleaving peptide.
Zhang teaches that CARs are engineered receptors that can graft an arbitrary specificity onto an immune effector cell (T cell) (instant claim 8). CARs include three parts: (1) an extracellular (instant claim 13) antigen recognition domain of the single-chain Fragment variant (scFv) (instant claim 11) derived from an antibody (instant claim 10), (2) a transmembrane domain and (3) an intracellular T cell activation domain of CD3ζ. (instant claim 9) (page 1, Background section). The third-generation CARs are made by combining multiple signaling domains to augment potency with stronger cytokine production and killing ability (page 3, Third generation section) (instant claim 9). CAR-T cell therapy is designed to redirect a patient’s or donor’s T cells to specifically target (a tumor antigen) and destroy tumor cells (page 1, Background section) (instant claim 12).
Zhang does not teach the CAR transcriptionally linked to IRP-2 by a sequence encoding a self-cleaving peptide.
Liu teaches a systematic comparison of 2A peptides for cloning multi-genes in a polycistronic vector (title, entire article). The construction of a multi-gene co-expression vector with 2A sequences and a schematic representation of the mechanism of “self-cleaving” 2A peptides is taught in Figure 1(A). Basically, Gene 1 and Gene 2 are linked by the 2A sequence in one construct (instant claims 14-16). Figure 2 teaches bi-cistronic 2A constructs including M-T2A-GFP construct where the two genes (M and GFP) are separated by the T2A sequence (instant claim 17).
It would be obvious to one of ordinary skill in the art to combine the teachings of Cullen, Barrett and Zhang to select a lymphocyte expressing both a synthetic IRP-2 (as discussed above) and a CAR to arrive at the claimed invention. It would further be obvious that the CAR would comprise an antigen biding domain (an antibody or a scFv fragment binding a tumor antigen on the cell surface), a transmembrane domain and one or more signaling domains as taught by Zhang. It would further be obvious to generate such a lymphocyte by using a bicistronic construct as taught by Liu where the IRP-2 gene is linked to the CAR polynucleotide by a self-cleaving peptide, such as 2A or T2A, to arrive at the claimed invention. One of ordinary skill would have been motivated to do so because IRP-2 overexpression would lead to the proliferation of the CAR T cell when stimulated with an tumor antigen eliciting stronger cytokine production and killing ability. There would be a reasonable expectation of success because CAR-T cell therapy is designed to redirect a patient’s or donor’s T cells to specifically target and destroy tumor cells.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IMMA BARRERA whose telephone number is (571) 272-0674. The examiner can normally be reached Monday - Friday 9 to 5.
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/IMMA BARRERA/
Examiner, Art Unit 1671
/JANET L ANDRES/ Supervisory Patent Examiner, Art Unit 1671