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 .
Status of Application, Amendments and/or Claims
The amendment and Applicant’s arguments, filed 18 November 2025, have been entered in full. Claims 2, 4-6, 15, 17, 19, 20, 22-25, 28, 30-38, 40-57, 59-71 are canceled. Claims 7-14, 26 are withdrawn from consideration as being drawn to a non-elected invention. New claims 72 and 73 are added.
Claims 1, 3, 16, 18, 21, 27, 29, 39, 58, 72 and 73 are under examination.
Information Disclosure Statement
The information disclosure statement(s) (IDS) (filed 18 November 2025) was received and complies with the provisions of 37 CFR §§1.97, 1.98 and MPEP § 609. It has been placed in the application file and the information referred to therein has been considered as to the merits.
Withdrawn Objections And/Or Rejections
The objection to the drawings as failing to comply with 37 CFR 1.84(p)(5), as set forth at pages 3-4 of the previous Office Action (16 July 2025), is withdrawn in view of the amendment (18 November 2025).
The rejection to claims 1-3, 16, 18, 21, 27, 29, 39 and 58 under 35 U.S.C. 102(a2) as being anticipated by Vijayanand et al. (US 2022/0033464; published Feb 3, 2022, priority date Aug 24, 2018), as set forth at pages 6-7 of the previous Office Action (16 July 2025), is withdrawn in view of the amendment (18 November 2025).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 18, 21, 27, 29, 39 and 58 remain rejected under 35 U.S.C. 102(a2) as being anticipated by Cobbold et al. (US 2022/0170044; published June 2, 2022, priority Feb 8, 2019). The basis for this rejection is set forth at pages 4-6 of the previous Office Action (16 July 2025).
APPLICANT’S ARGUMENTS Applicant argues that Cobbold fails to disclose every limitation of amended claim 1. Applicant states that previously, Claim 1 recited, "A composition comprising immune cells engineered to express B-cell lymphoma 6 (BCL6) and one or more cell survival-promoting genes." Applicant argues that the Office stated that Cobbold teaches "immune cells" that include "T-cells, natural killer cells and T-helper cells" (paras 0010 and 0011)."
Applicant submits that Claim 1 has been amended to recite "allogenic engineered immune cells that express B-cell lymphoma 6 (BCL6) and B-cell lymphoma 2L1 (Bcl-xL)”. Applicant argues that Cobbold does not teach allogenic engineered immune cells, nor does Cobbold teach allogenic engineered T cells expressing BCL-6 and BCL-xL. Applicant argues that instead, Cobbold describes T cells overexpressing BCL-6 with BCL-2 or BCL-xL alone.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. Cobbold et al. teach genes that are advantageous in modifying immune cells to enhance their function are an aspect of the invention. Cobbold et al. teach methods for modifying immune cells to enhance their function are an aspect of the invention (para 0011). Cobbold et al. teach immune cell survival-enhancing genes include anti-apoptotic genes such as Survivin, Bcl2, Bcl6 and Bcl-XL (para 0013). Cobbold et al. teach “immune cell survival-enhancing genes are provided to immune cells using transposon vectors. The benefit of using a transposon to deliver combinations of genes to the immune cell is that a transposase typically integrates all of the DNA between the transposon ITRs into the genome of the immune cell. Thus multiple genes can be introduced simultaneously” (para 0015).
Contrary to the presented arguments, Cobbold’s teaching of T-cells transfected with genes encoding Bcl2 and Bcl6 in Figure 4 is just one embodiment of the invention. MPEP 2123 [R-5] II states disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or non-preferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). The teachings of Cobbold et al. encompass T cells overexpressing BCL-6 with BCL-xL.
2. “Allogenic” refers to cells, tissues, or genetic material taken from a donor who is genetically different from the recipient but belongs to the same species.
Cobbold et al. teach “primary T-cells from 3 donors transfected with a gene encoding Bcl-XL” (para 0022). Cobbold et al. teach “examples of immune cells include leucocytes, lymphocytes, macrophages, neutrophils, dendritic cells, lymphoid cells, mast cells eosinophils basophils and natural killer cells. Lymphocytes include B and T lymphocytes. T lymphocytes include killer T cells, helper T cells and gamma delta T cells. Immune cells can be primary cells isolated from a subject or can be the result of further culturing including in the form of a cell line. Immune cells can be the subject of genetic engineering in addition to that described herein, e.g., expression of a CAR-T receptor” (para 0058).
The scientific reasoning and evidence as a whole indicates that the rejection should be maintained.
NEW CLAIM REJECTIONS/OBJECTIONS
Claim Rejections-35 USC § 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph
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 18 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 18 recites, “the composition of claim 1, wherein the immune cells are derived from a donor that has not been diagnosed with cancer or are derived from an individual in need of treatment”.
Claim 1 recites, “allogenic engineered immune cells”. “Allogenic” refers to cells, tissues, or genetic material taken from a donor who is genetically different from the recipient but belongs to the same species.
The limitation “immune cells…are derived from an individual in need of treatment” (as recited in Claim 18) reads on immune cells that are “autologous”, which is defined as the individuals own immune cells.
Claim 18 fails to further limit claim 1. 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.
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.
Claims 1, 3, 16, 18, 21, 27, 29, 39 and 58 are rejected under 35 U.S.C. 103 as being unpatentable over Cobbold et al. (US 2022/0170044; published June 2, 2022, priority Feb 8, 2019) in view of Novik et al. (US 2017/0360836; published Dec. 21, 2017).
Cobbold et al. teach compositions for stable genetic modification of immune cells. Cobbold et al. teach that the genetic modifications can be used to produce immune cells for therapeutic purposes (abstract). Cobbold et al. teach stable genetic modifications of immune cells can be made by integrating a polynucleotide into the genome of the immune cell (para 0004). Cobbold et al. teach immune cells include T-cells, natural killer cells and T-helper cells (paras 0010 and 0011) (applies to claims 3 and 21). Cobbold et al. teach the integrated polynucleotides can be immune cell survival-enhancing genes including anti-apoptotic genes such as BCL6, BCL2 and Bcl-XL (para 0013). Cobbold et al. teach immune cell survival-enhancing genes are provided to the immune cells using vectors (para 0015) (applies to claim 1). Cobbold et al. teach immune cells can be primary cells isolated from a subject or from normal donors (paras 0022, 0058, 0150) (applies to claim 18). Cobbold et al. teach wherein the immune cells are engineered to express chimeric antigen receptors (CAR)(paras 0020, 0066) (applies to claim 29). Cobbold et al. teach genes encoding receptors that allow the immune cell to bind to antigens on the surface of a target cell may be introduced. Cobbold et al. teach introducing into T-cells a gene encoding a receptor capable of binding to an antigen, wherein binding of the receptor to a target cell which displays the antigen on its surface, causes the T-cell to kill the target cell, which can be used in the treatment of cancer (paras 0015, 0160 and 0247 and claims) (applies to claim 27). Cobbold et al. teach making modifications of immune cells such as T-cells to enhance their ability to kill tumor cells and to improve their ability to survive and proliferate. Cobbold et al. teach it is useful to be able to also incorporate into the genome of the cell a gene that provides a means of killing the modified immune cell. Examples of such "kill switches" include expression of an antigen that is efficiently recognized by an existing therapeutic agent (for example a surface-expressed antigen such as CD20 that is normally found exclusively on B-cells and is recognized and treated by the drug rituximab or CD19 that is normally found exclusively on B-cells and is recognized and treated by the drug blinotumomab) and an inducible caspase 9 suicide switch. Cobbold et al. teach engineered immune cells having cytotoxicity activity (paras 0066, 0173-0175) (applies to claim 39). Cobbold et al. teach a composition comprising engineered cells for the treatment of immune-related disorders and/or cancers (abstract, paras 0017, 0064) (applies to claim 58).
Cobbold et al. do not teach that the immune T cells are engineered to express one or more cytokines.
Novik et al. teach compositions and methods of use may increase the efficacy of a CAR T-cell cancer therapy (abstract). Novik et al. teach adoptive cell transfer (ACT), wherein immune cells are modified to recognize and attack their tumors. One example of ACT is when a patient's own cytotoxic T-cells, or a donor's, are engineered to express a chimeric antigen receptor (CAR T-cells) targeted to a tumor specific antigen expressed on the surface of the tumor cells (para 0003). Novik et al. teach using allogenic donor T cells (paras 0019, 0147, 0233). Novik et al. teach CAR-modified T-cell potency may be further enhanced through the introduction of additional genes, including those encoding proliferative cytokines (i.e., IL-12) thus producing “armored” fourth-generation CAR-modified T-cells (para 0140)(applies to claims 16).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a composition comprising allogenic engineered immune cells engineered to express B-cell lymphoma 6 (BCL6) and B-cell lymphoma 2L1 (Bcl-xL), wherein the immune cells are T cells comprising an endogenous T-cell receptor (TCR), or the immune cells are engineered to express one or more chimeric antigen receptors (CAR) and/or one or more T-cell receptors (TCR), as taught by Cobbold et al., by having the immune T cells express one or more cytokines, as taught by Novik et al. One of ordinary skill in the art before the effective filing date, would have been motivated to make such modifications and expect success because Novik et al. teach the “armored CAR technology” (i.e. CAR-modified T-cells encoding introduced additional genes such as proliferative cytokines) incorporates the local secretion of soluble signaling proteins to amplify the immune response within the tumor microenvironment with the goal of minimizing systemic side effects.
Claims 72 and 73 are rejected under 35 U.S.C. 103 as being unpatentable over Bkazar et al. (WO 2017/100403; REGENTS OF THE UNIVERSITY OF MINNESOTA, published June 15, 2017) in view of Sirenko et al. (WO 00/75291; NOVARTIS AG, published December 14, 2000), Spits et al. (CN 101778866-B, published November 26, 2014. See English translation of CN 101778866-B and English equivalent US 2010/0239593; published September 23, 2010) and Gu et al. (Journal of Molecular Science 19, 3455, 12 pages; published 3 November 2018).
Bkazar et al. teach induced pluripotent stem cells (iPSCs) derived from a T cell of a T cell subset; T cells derived from iPSCs derived from a T cell; methods of deriving iPSCs from a T cell; methods of deriving T cells from iPSCs including deriving a T cell of a T cell subset from an iPSC; methods of engineering chimeric antigen receptor (CAR)-expressing or T cell receptor (TCR)-expressing iPSC and methods of administering T cells. Bkazar et al. teach a method that includes differentiating an iPSC derived from a T cell of a T cell subset. Bkazar et al. teach a method that includes differentiating an iPSC derived from a T cell of a T cell subset to a differentiated cell. Bkazar et al. teach wherein the iPSC is preferably derived from a stem memory T cell, a central memory T cell, or a naive T cell. In some embodiments, the iPSC comprises a chimeric antigen receptor-expressing iPSC. Bkazar et al. teach that in some embodiments, the differentiated cell includes a T cell (abstract and pages 1-2). Bkazar et al. teach an inducible BCL6 construct comprising a reverse tetracycline-controlled trans-activator (rtTA) designed to express the BCL6 protein in T cells (page 10, lines 3-12 and page 20, lines 13-21 and page 39, lines 13)(applies to claims 72 and 73). Bkazar et al. teach the use of non-viral and viral vectors, including those from lentivirus (page 17)(applies to claims 72 and 73).
Bkazar et al. do not teach a construct comprising BCL-xl, wherein Bcl-xl is expressed. Bkazar et al. teach a tet regulatory mechanism but do not explicitly teach that the tet regulatory mechanism can be located on a lentiviral vector.
Sirenko et al. teach a construct designed to express the BCL-xl protein in T cells (abstract, page 1, lines 1-3; page 6, 3rd paragraph; page 9, 4th paragraph; page 16, 2nd paragraph). Sirenko et al. teach vectors to include viral vector based on lentivirus (page 11, last paragraph-page 12, first paragraph)(applies to claims 72 and 73).
Spits et al. teach a construct comprising a nucleotide sequence encoding BCL6 and encoding a Bcl-xL. Spits et al. teach that the construct also includes an inducible promoter system, such as Tet-on, Tet-off system (See English Translation, para 0107)(applies to claims 72 and 73).
Gu et al. teach that chimeric antigen receptor T-cell therapy has shown great potential fighting against cancer. Gu et al. teach that despite the encouraging clinical success achieved in recent years, the potentially dangerous side effects associated with CAR-T therapies remain a major concern in its clinical application, such as cytokine release syndrome (CRS), neurotoxicity, and low blood cell counts. Gu et al. teach that to overcome these potential limitations, the tetracycline regulatory system might be an ideal alternative since transgene expression can be regulated by a very small dose of doxycycline (Dox) without the need to kill the CAR-T cells. Gu et al. teach that in typical Tet-on systems, a reverse tetracycline-controlled trans-activator (rtTA) can bind with the tetracycline-responsive element (TRE) promoter in the presence of doxycycline and activates transcription. Gu et al. teach an all-in-one Tet-on system into the third-generation lentiviral vector containing a CD19CAR construct, to explore the feasibility of regulating CD19CAR T-cell activity by doxycycline (pages 1-2).
It would have been obvious for one of ordinary skill in the art before the effective filling date to modify a composition comprising allogenic engineered immune cells engineered to express B-cell lymphoma 6 (BCL6) and has a tet regulatable mechanism, wherein the vector is a viral vector based on lentivirus, wherein the immune cells are T cells comprising an endogenous T-cell receptor (TCR), or the immune cells are engineered to express one or more chimeric antigen receptors (CAR) and/or one or more T-cell receptors (TCR), as taught by Bkazar et al., by combining it with a composition comprising allogenic engineered immune cells engineered to express B-cell lymphoma 2L1 (BCL-xL), wherein the immune cells are T cells comprising an endogenous T-cell receptor (TCR), or the immune cells are engineered to express one or more chimeric antigen receptors (CAR) and/or one or more T-cell receptors (TCR), wherein the vector is a viral vector based on lentivirus as taught by Sirenko et al., wherein BCL6 and Bcl-xL and a tet regulatory mechanism are all located on a lentiviral vector as taught by Spits et al. and Gu et al.
One of ordinary skill in the art before the effective filing date, would have been motivated to make such modifications and expect success for the following reasons. BCL6 and Bcl-xl are anti-apoptotic proteins, so it would be obvious to have the BCL6 and BCL-xL genes recombinantly expressed in engineered immune cells immune cells that might be used for in vivo treatment. Furthermore, Spits teaches a construct that comprises both the BCL6 gene and the Bcl-xL gene, which allows the skilled artisan the ease of transfecting (because they are on the same construct) into immune cells. Lastly, all of the references teach lentiviral vectors and/or tet regulatory mechanism. In particular, Spits et al. teach a construct comprising a nucleotide sequence encoding BCL6 and a nucleotide sequence encoding a Bcl-x and an inducible promoter systems, such as Tet-on, Tet-off system. Gu teaches the motivation of using tet regulatory mechanism on lentiviral vectors as it provides a way to regulate transgene expression while avoiding potential side effects. Based on all of this, it would be obvious to combine the teachings of the instant references.
Conclusion
No claims are allowed.
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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/R.M.D/Examiner, Art Unit 1647 2/24/2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647