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 .
Claims 1-20 are under consideration.
Rejections Maintained
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-3, 5, and 7-8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bamdad (Bamdad, et al., WO 2019/173815; Published 9/12/2019; Priority to 03/09/2018 by way of US 62/640,697, of record).
Bamdad teaches compositions comprising a MUC1* extracellular domain peptide attached to a surface and an immune cell that bears a receptor to the peptide (Bamdad, Abstract). Bamdad teaches that the cleaved form MUC1, dubbed MUC1*, transmembrane protein is a growth factor receptor that drives the growth of over 75% of human cancers (Bamdad, ¶ 0004). Bamdad teaches an aspect of the invention that is a cell comprising a chimeric antigen receptor (CAR) with an extracellular domain that binds to a MUC1* transfected or transduced cell that is an immune cell that is a T cell, NK cell, dendritic cell or mast cell (Bamdad, ¶ 0075). Bamdad also teaches immune cells that are transfected or transduced with cleavage enzymes for the treatment of MUC1 positive cancer with cleavage enzymes that are MMP8 (Bamdad, ¶ 00100-00101). Bamdad teaches that in one example, the addition of the catalytic domain of MMP9 caused a dramatic increase in the killing of T47D MUC1 positive breast cancer cells by CAR44 CAR-T cells (Bamdad, ¶ 00250). Regarding claims 1-2, 5 and 7, Bamdad discloses T and NK cells transfected or transduced with a CAR as well as a cleavage enzyme that is MMP8 or a catalytically active fragment thereof (Bamdad, ¶ 00250).
Regarding claim 3, the transduced CAR/MMP8-comprising T cells and NK cells of Bamdad also satisfy claim 3 because “transduced” means the cells have been given a retrovirus comprising nucleic acid encoding for the CAR and MMP8 such that the cells express the genes within the construct and, as such, the transduced CAR/MMP8-comprising T cells and MK cells of Bamdad also satisfy instant claim 3.
Regarding claim 8, the CAR/MMP8-comprising T cells and NK cells of Bamdad also satisfy instant claim 8 because the cells of Bamdad are genetically modified immune cells expressing MMP8 and the patentability of a product does not depend on its method of production (see MPEP § 2113) and, as such, the CAR/MMP8-comprising T cells and NK cells of Bamdad are the same as immune cells isolated from peripheral blood.
Response to Arguments
Applicant's arguments filed 1/26/2026 have been fully considered but they are not persuasive.
Applicant’s arguments rest entirely on the amendments to claims 1, 10 and 16, which have been amended to specify that the MMP8 is in its active form, which is arrived at by cleavage of the MMP8 propeptide. Applicant argues that Bamdad does not teach a genetically modified immune cell expressing a mature form (emphasis added by Applicant) of an MMP, which Applicant argues is arrived at by cleavage of the propeptide from native MMP, citing ¶ 0017 of the instant Specification.
In response, Bamdad specifically refers to all of the MMP proteins disclosed by Bamdad as “cleavage enzymes” (Bamdad, ¶ 0250), which would not be an accurate descriptor if the MMP comprised a propeptide that rendered it unable to engage in enzymatic cleavage. As such, the MMPs disclosed by Bamdad at ¶ 0250 are inherently in their active/mature form.
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.
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.
Claim(s) 1-3, 5-12, 14, 16-17 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over by Bamdad (Bamdad, et al., WO 2019/173815; Published 9/12/2019; Priority to 03/09/2018 by way of US 62/640,697, of record) as applied to claims 1-3, 5 and 7-8 above and in further consideration of the Bamdad reference.
The teachings of Bamdad are discussed above.
Bamdad does not teach that the MMP8/CAR expressing immune cells also express a cytokine. Bamdad does not teach a method of treating a solid tumor that is breast cancer, said method comprising administering the anti-MUC1*-CAR/MMP8 expressing T-cells of Bamdad in combination with chemotherapy and/or immunotherapy. Bamdad does not teach a method of treating a solid tumor that is breast cancer, said method comprising administering the anti-MUC1*-CAR/MMP8 expressing NK-cells of Bamdad in combination with chemotherapy and/or immunotherapy. Bamdad does not teach myeloid cells that are CAR-DCs that express the MMP8 and CAR of Bamdad.
In addition to the teachings above, Bamdad also teaches immune cells that are T or NK cells that express a CAR and a non-CAR species that is a cytokine that is IL-7 (Bamdad, ¶ 00257). Moreover, Bamdad teaches that the compositions of Bambad is administered in combination with chemotherapy agents and targeted biologicals such as ADCs (same as immunotherapies). Bamdad also teaches that the CAR-expressing T cells were prepared by culturing human T cells and then transducing with constructs comprising lentiviral expression vectors (Bamdad, ¶ 00297-00300).
It would be prima facie obvious to one of ordinary skill in the art to apply the teachings of Bamdad to the treatment of solid tumors that are breast tumors and form a method of treating breast cancer, said method comprising administering the anti-MUC1*-CAR/MMP8 expressing T-cells of Bamdad to a patient having a MUC1 expressing breast tumor in combination with chemotherapy and/or immunotherapy. One of ordinary skill in the art would be motivated to do this in order to better treat breast cancer. One of ordinary skill in the art would have a reasonable expectation of success treating MUC1 expressing breast cancer by administering the anti-MUC1*-CAR/MMP8 expressing T-cells of Bamdad because: 1) Bamdad teaches T cells that express both an anti-MUC1* CAR and MMP8, 2) Bamdad teaches that the addition of a the catalytic domain of another MMP enzyme to adherent cell culture growing T47D breast cancer cells greatly enhanced the ability of CAR-T cells to target and kill the breast cancer cells in vitro and 3) one of ordinary skill in the art would reasonably expect this correlation between MMP catalytic activity and increased CAR-cell based targeting killing of cancer cells would be present in vivo as well. One of ordinary skill in the art would have a reasonable expectation of success further administering chemotherapeutics and/or immunotherapeutics in conjunction with the MMP8-CAR-T cells of Bamdad because Bamdad teaches administration of the modified immune cells of Bamdad in conjunction with chemotherapeutics and/or immunotherapeutics.
It would be prima facie obvious to one of ordinary skill in the art to apply the teachings of Bamdad to the treatment of solid tumors that are breast tumors and form a method of treating breast cancer, said method comprising administering the anti-MUC1*-CAR/MMP8 expressing NK cells of Bamdad to a patient having a MUC1 expressing breast tumor in combination with chemotherapy and/or immunotherapy. One of ordinary skill in the art would be motivated to do this in order to better treat breast cancer. One of ordinary skill in the art would have a reasonable expectation of success treating MUC1 expressing breast cancer by administering the anti-MUC1*-CAR/MMP8 expressing NK-cells of Bamdad because: 1) Bamdad teaches NK cells that express both an anti-MUC1* CAR and MMP8, 2) Bamdad teaches that the addition of a the catalytic domain of another MMP enzyme to adherent cell culture growing T47D breast cancer cells greatly enhanced the ability of CAR-T cells to target and kill the breast cancer cells in vitro and 3) one of ordinary skill in the art would reasonably expect this correlation between MMP catalytic activity and increased CAR-cell based targeting killing of cancer cells would be present in vivo as well. One of ordinary skill in the art would have a reasonable expectation of success further administering chemotherapeutics and/or immunotherapeutics in conjunction with the MMP8-CAR-NK cells of Bamdad because Bamdad teaches administration of the modified immune cells of Bamdad in conjunction with chemotherapeutics and/or immunotherapeutics.
It would also be prima facie obvious to one of ordinary skill in the art to make dendritic cells (a type of myeloid immune cell) expressing the MMP8 and CAR of Bamdad in view of the teachings of Bamdad. Bamdad teaches of dendritic cells expressing the CAR of Bamdad at ¶ 0074 but does not explicitly teach dendritic cells further expressing MMP8. However, the fact that Bamdad teaches MMP activity greatly enhanced the cancer killing activity of CAR-T cells would lead one of ordinary skill in the art to reasonably deduce that MMP activity would also enhance CAR-DC-based antigen presentation and T cell activation with a reasonable expectation of success because CAR-T-based cancer cell killing and CAR-DC-based antigen presentation and T cell activation are CAR-mediated processes initiated when a CAR expressed on a T cell or DC binds to its antigen.
It would also be prima facie obvious to one of ordinary skill in the art to further modify the MMP8/CAR T cells of Bamdad to further express the IL-7 cytokine also taught by Bamdad. One of ordinary skill in the art would be motivated to do this to add an immunostimulatory element to the MMP8/CAR-T cells of Bamdad. One of ordinary skill in the art would have a reasonable expectation of success further modifying the MMP8/CAR T cells of Bamdad to express IL-7 because Bamdad teaches that the modified immune cells of Bamdad can be modified to express IL-7, which would add its well-known immunostimulatory effect to the invention.
Response to Arguments
Applicant's arguments filed 1/26/2026 have been fully considered but they are not persuasive.
Applicant again argues that the amendments to the claims specifying the MMP is in its catalytically active form distinguish the instant claimed invention from Bamdad, who Applicant again argues does not disclose mature MMP8. Applicant points to how MMP8, in its mature form, is capable of degrading ECM material and how ECM degradation surrounding tumors is particularly relevant to the ability of the instant claimed invention to treat solid tumors, pointing to examples 2 and 3, which demonstrate that the instant claimed MMP-comprising genetically modified immune cells are capable of degrading ECM.
In response, Bamdad specifically refers to all of the MMP proteins disclosed by Bamdad as “cleavage enzymes” (Bamdad, ¶ 0250), which would not be an accurate descriptor if the MMP comprised a propeptide that rendered it unable to engage in enzymatic cleavage. As such, the MMPs disclosed by Bamdad at ¶ 0250 are inherently in their active/mature form. Because the MMPs of Bamdad are inherently in their active form, they would be able to degrade ECM every bit as well as the corresponding instant claimed MMP.
Applicant also argues that none of the working examples of Bamdad use immune cells that do not comprise a co-expressed MMP (mature or otherwise) at their surface. In response, this is not relevant as Bamdad specifically discloses genetically modified immune cells comprising a cleavage enzyme that is MMP8 (Bamdad, ¶ 0250).
Claim(s) 1-12, 14, 16-17 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over by Bamdad (Bamdad, et al., WO 2019/173815; Published 9/12/2019; Priority to 03/09/2018 by way of US 62/640,697, of record) as applied to claims 1-3, 5-12, 14, 16-17 and 19 above and in further view of Parayath (Parayath, et al., Nature Communications 2020 11:6080, of record).
The teachings of Bamdad are discussed above.
Bamdad does not teach that the MMP8 and CAR are encoded by mRNA constructs.
Parayath teaches on the subject of in vitro transcribed (IVT) CAR or TCR mRNA for instantly reprogramming circulating T cells to recognize disease-specific antigens (Pravayath, Abstract). Parayath teaches that mRNA nanocarriers (same as mRNA construct) were able to successfully transfect T cells with both CAR and TCR transgenes (Parayath, p 3, ¶ 1).
It would be prima facie obvious to one of ordinary skill in the art to use the mRNA nanocarrier IVT CAR method of Parayath to transfect T cells to express the CAR and MMP8 of Bamdad. One of ordinary skill in the art would be motivated to do this in order to have a method to express the MMP8/CAR of Bamdad on any T cell and not simply T cells of certain lines. One of ordinary skill in the art would have a reasonable expectation of success using the mRNA nanocarrier IVT CAR method of Parayath to transfect T cells to express the CAR and MMP8 of Bamdad because Parayath teaches that the mRNA nanocarrier IVT CAR method of Parayath was able so successfully transfect T cells with CARs and TCRs.
Response to Arguments
Applicant presents no arguments specific to this rejection other than reiterating previously addressed arguments.
Claim(s) 1-3 and 5-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over by Bamdad (Bamdad, et al., WO 2019/173815; Published 9/12/2019; Priority to 03/09/2018 by way of US 62/640,697, of record) as applied to claims 1-3, 5-12, 14, 16-17 and 19 above and in further view of Nanda (Nanda, et al., JAMA Oncol 2020 6(5):676, of record).
The teachings of the Bamdad reference are discussed above.
Bamdad does not teach that the MMP8/CAR NK cells or MMP8/CAR T Cells are administered in a method of treating breast cancer that also comprises administration of doxorubicin and an anti-PD1 antibody.
Nanda teaches of a study of pembrolizumab (an anti-PD-1 antibody) plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer (Nanda, Objective). Nanda teaches that patients in the pembrolizumab group were administered pembrolizumab (an anti-PD1 antibody) as well as doxorubicin (Nanda, p 678, ¶ 2). Nanda teaches that the pembrolizumab group vastly outperformed the control group in ERBB2- populations HR+/ERBB2- populations and TNBC populations (Nanda, Table 1).
It would be prima facie obvious to one of ordinary skill to combine the method of treating breast cancer taught by Bamdad, said method comprising administering anti-MUC1* CAR/MPP8-NK cells or anti-MUC1* CAR/MPP8-T cells with the method of treating breast cancer taught by Nanda, said method comprising administration of doxorubicin and the administration of pembrolizumab to form a combined method wherein one or both of the CAR/MPP8 modified NK and or T cells are administered in conjunction with the doxorubicin and pembrolizumab of Nanda. One of ordinary skill in the art would be motivated to do this in order to better treat breast cancer. It is considered prima facie obvious to combine two art elements, each of which being taught in the prior art as useful for the same purpose together to form something to be used for that very same purpose is a prima facie obvious combination (see MPEP § 2144.06). In the instant case, Bamdad teaches a method of treating breast cancer comprising administering anti-MUC1* CAR/MPP8-NK cells or anti-MUC1* CAR/MPP8-T cells and Nanda teaches a different method of treating breast cancer comprising administering pembrolizumab as well as doxorubicin. Combining the anti-MUC1* CAR/MPP8-NK cells or anti-MUC1* CAR/MPP8-T cells of Bamdad with the pembrolizumab /doxorubicin of Nanda to form a method of treating breast cancer would be an obvious combination that would an afford one of ordinary skill in the art a reasonable expectation of success because you’re just combining two methods already taught to treat breast cancer and using the combined method to treat breast cancer.
Response to Arguments
Applicant presents no arguments specific to this rejection other than reiterating previously addressed arguments.
Conclusion
Claims 1-20 are rejected.
No claims are allowed.
THIS ACTION IS MADE FINAL. 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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/SYDNEY VAN DRUFF/ Examiner, Art Unit 1643
/JULIE WU/ Supervisory Patent Examiner, Art Unit 1643
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