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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/07/2026 has been entered.
Rejections/Objections Withdrawn
All 35 USC §§ 102 and 103 rejections have been withdrawn in view of claim amendments.
New Rejections Necessitated by Amendment
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) in view of Borunda (Borunda, et al., US 2004/0156827A1; Published 8/12/2004; Priority to 9/17/1999 via MX998515).
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).
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).
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.
Bambdad does not teach that the genetically engineered CAR/MMP8-comprising immune cells of Bambdad comprise a nucleic acid that encodes the active sequence of MMP8 but does not encode the native, inactivating propeptide. 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.
Borunda teaches on the subject of gene therapies comprising delivery of genes encoding both active and latent MMP8 (Borunda, Abstract). Borunda teaches of a transfection-ready nucleic acid construct comprising the PCR product coding for the MMP8 catalytic domain, which lacks the inactivating propeptide (Borunda, ¶ 0075).
It would be prima facie obvious to use the catalytic domain only MMP8 nucleic acid construct of Borunda as the MMP8 gene used to transfect the CAR/MMP8-comprising genetically modified immune cells of Bamdad. One of ordinary skill in the art would be motivated to do this to produce CAR/MMP8-comprising immune cells that only produce active MMP8. Bamdad teaches genetically modified immune cells comprising “cleavage enzymes” at Bamdad ¶ 00100-00101 and teaches genetically modified CAR/MMP8 cells transduced by a “cleavage enzyme” that is MMP8 or a catalytically active fragment thereof at Bamdad ¶ 002500. One of ordinary skill in the art would have a reasonable expectation of success using the MMP8 nucleic acid construct of Borunda (that comprises the MMP8 catalytic domain and not the native inactivating propeptide) to transfect the CAR/MMP8-comprising genetically modified immune cells of Bamdad because Bamdad teaches transfection with MMP8 “catalytically active fragments” and Borunda teaches a specific MMP8 catalytically active fragment nucleic acid construct suitable for transfection.
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 08/07/2026 have been fully considered but they are not persuasive.
None of Applicant’s arguments presented 08/07/2026 apply to the rejection above, as all of Applicant’s arguments relate to Applicant’s allegations that the Bamdad reference fails to sufficiently teach a nucleic acid construct that contains nucleic acid material encoding the active domain of MMP8 but does not encode the inactivating propeptide. These arguments are not relevant to the instant rejection made in view of the Borunda reference because the Borunda reference provides a specific, transfection ready nucleic acid construct that contains nucleic acids encoding the catalytic portion of MMP8 but not the inactivating propeptide (Borunda, ¶ 0075). The Bamdad reference teaches transfection of genetically modified immune cells with “catalytically active fragments” of MMP8 at (Bamdad, ¶ 002500) and the Borunda reference provides a specific, transfection-ready nucleic acid construct encoding a specific MMP8 catalytically active fragment.
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) in view of Borunda (Borunda, et al., US 2004/0156827A1; Published 8/12/2004; Priority to 9/17/1999 via MX998515), 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 and Borunda are discussed above.
Bamdad and Borunda do 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 and Borunda. 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's arguments filed 08/07/2026 have been fully considered but they are not persuasive.
Applicant asserts that the Parayath reference fails to make up for the Bamdad’s alleged lack of teaching of a specific nucleic acid construct that encodes catalytically active MMP8 but does not encode the inactivating propeptide. These arguments have been addressed above and by inclusion of the Borunda reference.
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) in view of Borunda (Borunda, et al., US 2004/0156827A1; Published 8/12/2004; Priority to 9/17/1999 via MX998515), 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 Bamdad and Borunda are discussed above.
Bamdad and Borunda do 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's arguments filed 08/07/2026 have been fully considered but they are not persuasive.
Applicant asserts that the Nanda reference fails to make up for the Bamdad’s alleged lack of teaching of a specific nucleic acid construct that encodes catalytically active MMP8 but does not encode the inactivating propeptide. These arguments have been addressed above and by inclusion of the Borunda reference.
Conclusion
Claims 1-20 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sydney Van Druff whose telephone number is (571)272-2085. The examiner can normally be reached 10 am - 6 pm.
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/SYDNEY VAN DRUFF/ Examiner, Art Unit 1643
/JULIE WU/ Supervisory Patent Examiner, Art Unit 1643
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