DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 12/22/2025 has been entered.
Claims status
Claims 3-9 is/are cancelled. Claims 1, 10, 11, 21 is/are currently pending and is/are under examination.
Withdrawn Objections
The objections presented herein represent the full set of objections currently pending in this application. Any objections not specifically reiterated are hereby withdrawn.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim recites lentiviral vector “carrying” a recombinant nucleic acid. Standard claim language in the art generally refers to lentiviral vectors “comprising” nucleic acids. The term “comprising” is more appropriate since vectors do not carry a nucleic acid. Replacement of the term “carrying” with “comprising” is recommended. Appropriate correction is required.
Claim 1 is objected to because of the following informalities: Claim recites transmembrane antigens “having” cDNA sequence in options (i-v). Antigens are not DNA sequences but are proteins that are encoded by cDNA sequences. Replacement of the term “having” with “encoded by” in each of options (i-v) is recommended. Appropriate correction is required.
Claim 21 is objected to because of the following informalities: Claim recites a conjunction (“and” at line 13) at the end of the claim without any additional limitations that follow the said conjunction. Removal of this conjunction and preferably using a conjunction after the “wherein […] SUP-B15 cell;” in line 10 is recommended. Appropriate correction is required.
Claim Rejections - 35 USC § 112(d) – Moot
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.
Rejections of Claims 8 and 9 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 are moot due to claim cancellation.
Claim Rejections - 35 USC § 112(b) – New, in light of amendments
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.
Rejection of Claim 21 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 is withdrawn in light of claim amendment.
Claims 1, 10, 11 are 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 1 is directed to a product which is a human target cell. However, the claim appears to recite an active method step of “transducing the human target cell with a lentiviral vector”. It is unclear if the claimed cell is transduced with the claimed vector or not such that the structure of the claimed cell is unclear. For the purpose of compact prosecution, the claim(s) 1 is/are interpreted as “
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “wherein the transmembrane antigen is a tumor associated antigen, a tumor specific antigen, or a patient- and tumor specific antigen”, and the claim also recites “wherein the transmembrane antigen is” PD-L1, CD33, CD123, HER-2, or CD20 with specifically recited sequences, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. For the purpose of compact prosecution, the claim(s) 1 is/are interpreted as “
Claim 10 recites “The recombinant human target cell of claim 9”. Since claim 9 is cancelled, the recombinant human target cell of claim 9 is indefinite. For the purpose of compact prosecution, the claim(s) 10 is/are interpreted as “The recombinant human target cell of claim 1[[9]]”.
Claim 11 recites “The recombinant human target cell of claim 9”. Since claim 9 is cancelled, the recombinant human target cell of claim 9 is indefinite. For the purpose of compact prosecution, the claim(s) 11 is/are interpreted as “The recombinant human target cell of claim 1[[9]]”.
Claim Interpretation
Claim 1, 10, 11 and 21 are directed to a SUP-B15 cell comprising one of the recited transmembrane antigens. Claims further recite functional features of the claimed SUP-B15 cell, reciting that the claimed cell exhibit a spontaneous lysis of equal to or less than 20%, 15% or 10% in the presence of a CAR-T or NK cell at various effector cell to SUP-B15 cell ratios. In [0039], the specification states that “the terms "spontaneous lysis" and "non-specific killing" with regard to target cells refer to cell death of the target cells that is not attributable to a target specific (i.e., specific to the recombinant target antigen expressed in the target cells) cell killing event, wherein the target specific cell killing event is ADCC (via an antibody binding the recombinant target antigen) and/or CAR-mediated cytotoxicity (via the CAR ectodomain binding the recombinant target antigen)”. Thus, functional features of the claimed SUP-B15 cell pertaining to spontaneous lysis in the presence of a CAR-T or NK cell are an inherent feature of the SUP-B15 cell despite the claimed transmembrane antigen and not due to these transmembrane antigen. Thus, the claimed functional features pertaining to spontaneous lysis are met by a SUP-B15 cell itself. A prior art teaching SUP-B15 teaches a cell with the claimed functional features that are inherent.
Claim Rejections - 35 USC § 103 – New, in light of amendments
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Rejection of Claims 1, 3, 5, 8-11 and 21 under 35 U.S.C. 103 as being unpatentable over Chen et al (Stromal cells attenuate the cytotoxicity of imatinib on Philadelphia chromosome-positive leukemia cells by up-regulating the VE-cadherin/β-catenin signal. Leukemia Research, Volume 38, October 2014; reference of record) and Uherek et al (Retargeting of natural killer–cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction. Blood, Volume 100, August 2002; reference of record) in view of Hasenkamp et al (Resistance Against Natural Killer Cell Cytotoxicity: Analysis of Mechanisms. Scandinavian Journal of Immunology, Volume 64, 2006; reference of record) is withdrawn in light of amendment to claim 1 requiring specifically recited sequences.
Rejection of Claims 1, 4, 5, 8-11 and 21 under 35 U.S.C. 103 as being unpatentable over Chen et al (Stromal cells attenuate the cytotoxicity of imatinib on Philadelphia chromosome-positive leukemia cells by up-regulating the VE-cadherin/β-catenin signal. Leukemia Research, Volume 38, October 2014; reference of record) and Hoseini et al (Acute myeloid leukemia targets for bispecific antibodies. Blood Cancer Journal, Volume 7, February 2017; reference of record) in view of Hasenkamp et al (Resistance Against Natural Killer Cell Cytotoxicity: Analysis of Mechanisms. Scandinavian Journal of Immunology, Volume 64, 2006; reference of record) is withdrawn in light of amendment to claim 1 requiring specifically recited sequences.
Rejection of Claims 6 and 7 under 35 U.S.C. 103 as being unpatentable over Chen et al (Stromal cells attenuate the cytotoxicity of imatinib on Philadelphia chromosome-positive leukemia cells by up-regulating the VE-cadherin/β-catenin signal. Leukemia Research, Volume 38, October 2014; reference of record) and Uherek et al (Retargeting of natural killer–cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction. Blood, Volume 100, August 2002; reference of record) in view of Hasenkamp et al (Resistance Against Natural Killer Cell Cytotoxicity: Analysis of Mechanisms. Scandinavian Journal of Immunology, Volume 64, 2006; reference of record) as applied to claims 1 above, further in view of Boissel et al (Comparison of mRNA and lentiviral based transfection of natural killer cells with chimeric antigen receptors recognizing lymphoid antigens. Leukemia & Lymphoma, Volume 53, May 2012) is moot due to claim cancellation.
Claims 1, 10, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (Leukemia Research, Volume 38, October 2014; reference of record) and NM_002183.4 (Homo sapiens interleukin 3 receptor subunit alpha (IL3RA), transcript variant 1, mRNA; available at <https://www.ncbi.nlm.nih.gov/nucleotide/NM_002183.4?report=
genbank&log$=nucltop&blast_rank=1&RID=0VNZRC9C016> and PTO-892, May 2019) in view of Hacker (ed.) (Recombinant Protein Expression in Mammalian Cells: Methods and Protocols, Methods in Molecular Biology, vol. 1850, 2018) as evidenced by Hasenkamp et al (Scandinavian Journal of Immunology, Volume 64, 2006; reference of record).
Regarding claim 1, in view of 112b issues noted above, Chen teaches a recombinant human target cell comprising a vector comprising a promoter operably coupled to a sequence encoding a transmembrane antigen (Materials and Methods: Stable overexpression of VE-cadherin in Ph+ leukemia cells). Chen teaches SUP-B15 as the recombinant human target cell (Materials and Methods: Stable overexpression of VE-cadherin in Ph+ leukemia cells).
Chen teaches a plasmid vector to deliver the sequence encoding the transmembrane antigen and a VE-cadherin transmembrane antigen (Materials and Methods: Stable overexpression of VE-cadherin in Ph+ leukemia cells).
Chen does not teach a lentiviral vector based delivery such that the SUP-B15 comprises a lentiviral vector. Chen does not teach a transmembrane antigen that is CD123 encoded by sequence SEQ ID NO: 1.
Hacker teaches well-known methods of transgene delivery for recombinant protein expression in mammalian cells (Preface, para 1). For transient gene expression, plasmid based delivery was known in the art. Chapter 1 teaches plasmid-based transient gene expression (Abstract; Introduction-para 2; Materials: Plasmid DNA preparation). For stable gene expression, lentiviral vector based gene delivery was known in the art. Chapter 4 teaches that “Lentiviral gene transfer represents a versatile and powerful method for genetic transduction of many cell lines and primary cells including “hard-to-transfect” cells. As a consequence of the integration of the recombinant lentiviral vector into the cellular genome the transgene is stably maintained and long term producing cells are established” (Abstract). Chapter 4 also teaches the method to generate lentiviral vectors using lentiviral vector plasmids wherein the transgene/cDNA encoding protein of interest is inserted (Figure 2, 3, Methods: 3.1 Virus Production in Helper Cells (See Note 4)). It states that “Various lentiviral vector systems are available that allow convenient cloning of the transgene (see Note 1)” (page 45, para 2). Finally, Chapter 4 also teaches the method to transduce cells with lentiviral vector (Methods: 3.5 Transduction of cells by lentiviral vectors). Thus, chapter 4 provides the requisite teachings to generate and use a lentiviral vector comprising any nucleotide sequences of insert.
NM_002183.4 teaches the cDNA sequence of human interleukin 3 receptor subunit alpha (=CD123), a transmembrane antigen, which identical to claimed SEQ ID NO: 1 (see Sequence alignment section below).
The combination of prior art cited above under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S., 82 USPQ2d 1385 (2007). Exemplary rationales that may support a conclusion of obviousness are from MPEP 2143.
In the present situation, rationale B (Simple Substitution of One Known Element for Another To Obtain Predictable Results) is applicable. MPEP 2143 guides that for rationale B “Office personnel must articulate the following: (1) a finding that the prior art contained a device (method, product, etc.) which differed from the claimed device by the substitution of some components (step, element, etc.) with other components; (2) a finding that the substituted components and their functions were known in the art; (3) a finding that one of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable; and (4) whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness”.
(1) The prior art of Chen comprises a recombinant SUP-B15 cell comprising a plasmid comprising a sequence encoding a transmembrane antigen which in Chen’s case is VE-Cadherin. Chen differs from the claimed recombinant SUP-B15 cell which recites the lentiviral vector comprising the sequence of SEQ ID NO: 1 encoding the transmembrane antigen of CD123.
(2) The substituted components were known in the art as taught by Hacker and NM_002183.4. Hacker taught lentiviral vectors for gene delivery to cells (Chapter 7) and NM_002183.4 taught a sequence encoding CD123 identical to claimed SEQ ID NO:1.
(3) As taught by Hacker, both plasmid and lentiviral vectors were routinely used in the art to deliver transgenes to human cells to generate recombinant human cells. An ordinary artisan could substitute a lentiviral vector in place of a plasmid vector and could further substitute the cDNA sequence of VE-Cadherin with the cDNA sequence of CD123 in the vector expecting predictable result of a SUP-B15 cell comprising a lentiviral vector comprising a sequence encoding CD123. Considering the sequence for CD123 was taught by NM_002183.4 and generation of lentiviral vectors to encode transgenes of interest was taught by Hacker, an ordinary artisan could simply substitute Chen’s plasmid vector with Hacker’s lentiviral vector and further, when generating the vector, an ordinary artisan could simply substitute Chen’s VE-Cadherin cDNA with CD123 cDNA. Such a substitution is predicted to result in a SUP-B15 with a lentiviral vector comprising CD123 transmembrane antigen instead of VE-Cadherin.
Further, as noted in the claim interpretation section, since Chen teaches a SUP-B15 cell, Chen meets the limitation pertaining to the claimed spontaneous lysis feature inherent to SUP-B15 cells. As further evidence, this inherent feature was also known in the art. Hasenkamp evidences SUP-B15 as NK cell-resistant cells (Abstract, page 448-col.1-para2) and evidences that SUP-B15 cells show less than 10% lysis in presence of NK cells at an effector cell to target cell ratio of 1 or less (as required for claims 1, 10, 11; Figure 1B).
Therefore, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR. Therefore, it would be obvious to a person of ordinary skill in the art to substitute the plasmid vector with a lentiviral vector and the VE-Cadherin cDNA sequence with the CD123 cDNA sequence to yield a predictable result of a SUP-B15 cell with lentiviral vector with CD123 cDNA.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (Leukemia Research, Volume 38, October 2014; reference of record) and NM_002183.4 (Homo sapiens interleukin 3 receptor subunit alpha (IL3RA), transcript variant 1, mRNA; available at <https://www.ncbi.nlm.nih.gov/nucleotide/NM_002183.4?report=
genbank&log$=nucltop&blast_rank=1&RID=0VNZRC9C016> and PTO-892, May 2019) as evidenced by Hasenkamp et al (Scandinavian Journal of Immunology, Volume 64, 2006; reference of record).
Regarding claim 21, Chen teaches a recombinant human target cell comprising a vector (= claimed recombinant nucleic acid) comprising a promoter operably coupled to a sequence encoding a transmembrane antigen (Materials and Methods: Stable overexpression of VE-cadherin in Ph+ leukemia cells). Chen teaches SUP-B15 as the recombinant human target cell (Materials and Methods: Stable overexpression of VE-cadherin in Ph+ leukemia cells).
Chen teaches a VE-cadherin transmembrane antigen (Materials and Methods: Stable overexpression of VE-cadherin in Ph+ leukemia cells).
Chen does not teach that the SUP-B15 comprises a transmembrane antigen that is CD123 encoded by sequence SEQ ID NO: 1.
NM_002183.4 teaches the cDNA sequence of human interleukin 3 receptor subunit alpha (=CD123), a transmembrane antigen, which identical to claimed SEQ ID NO: 1 (see Sequence alignment section below).
The combination of prior art cited above under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S., 82 USPQ2d 1385 (2007). Exemplary rationales that may support a conclusion of obviousness are from MPEP 2143.
In the present situation, rationale B (Simple Substitution of One Known Element for Another To Obtain Predictable Results) is applicable. MPEP 2143 guides that for rationale B “Office personnel must articulate the following: (1) a finding that the prior art contained a device (method, product, etc.) which differed from the claimed device by the substitution of some components (step, element, etc.) with other components; (2) a finding that the substituted components and their functions were known in the art; (3) a finding that one of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable; and (4) whatever additional findings based on the Graham factual inquiries may be necessary, in view of the facts of the case under consideration, to explain a conclusion of obviousness”.
(1) The prior art of Chen comprises a recombinant SUP-B15 cell comprising a sequence encoding a transmembrane antigen which in Chen’s case is VE-Cadherin. Chen differs from the claimed recombinant SUP-B15 cell which recites the transmembrane antigen to be CD123 encoded by SEQ ID NO: 1.
(2) The substituted component was known in the art as taught by NM_002183.4, that taught a sequence encoding CD123 identical to claimed SEQ ID NO:1.
(3) An ordinary artisan would substitute the cDNA sequence of VE-Cadherin with the cDNA sequence of CD123, taught by NM_002183.4, in the vector of Chen using routine methods such as used by Chen (2.4. Stable overexpression of VE-cadherin in Ph+ leukemia cells). Such a substitution is predicted to result in a SUP-B15 with CD123 transmembrane antigen instead of VE-Cadherin.
Further, as noted in the claim interpretation section, since Chen teaches a SUP-B15 cell, Chen meets the limitation pertaining to the claimed spontaneous lysis feature inherent to SUP-B15 cells. As further evidence, this inherent feature was also known in the art. Hasenkamp evidences SUP-B15 as NK cell-resistant cells (Abstract, page 448-col.1-para2) and evidences that SUP-B15 cells show less than 10% lysis in presence of NK cells at an effector cell to target cell ratio of 1 or less (Figure 1B).
Therefore, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR. Therefore, it would be obvious to a person of ordinary skill in the art to substitute the VE-Cadherin cDNA sequence with the CD123 cDNA sequence to yield a predictable result of a SUP-B15 cell with CD123.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments with respect to the U.S.C. 103 rejection of claim(s) have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
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Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATASHA DHAR whose telephone number is (571)272-1680. The examiner can normally be reached M-F 8am-4pm (EST).
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/MATASHA DHAR/Examiner, Art Unit 1632
Prosecution Insights