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, 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Sept. 2, 2025 has been entered.
Claim Status
Claims 1-2, 4-5, 7, 25, 29, 32, 39, and 51-52 are currently pending in this application.
Election/Restrictions
Applicant's election without traverse of Group I, claims 1-5, 7-9, 25, 29, 32, 35, 39, and 44, in the reply filed on July 9, 2024 is acknowledged. Claims 1-2, 4-5, 7, 25, 29, 32, 39, and 51-52 have been considered on the merits.
Benefit of Priority Claim
Acknowledgement is made of applicant’s claim for the benefit of the prior-filed application US 62/803,468 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c). The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of US 62/803,468 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application with regard to a transgene encoding TREM2 or CD2AP, therefore the earliest effective filing date of claims 1-2, 4-5, 7, and 51-52 is Feb. 10, 2020 based on PCT/US2020/017515.
Claim Interpretation
Claim 1 recites the term “HSPCs,” which is interpreted to encompass any population of cells wherein the cells are hematopoietic stem cells, hematopoietic progenitor cells, or a combination of the aforementioned cell types. And thus, it follows that claim 2 is interpreted to require those hematopoietic stem cells, hematopoietic progenitor cells, or the combination thereof be CD34+. In claim 51, the term “GEMys” is interpreted as typically used in the art to mean genetically engineered myeloid cells, but in view of claim 1, restricted to only those genetically engineered myeloid cells that are also some type of myeloid progenitor cell (i.e., a subtype of hematopoietic progenitor cell) and comprise the vector. See instant [0028], [0075]-[0077]). Similarly, claim 52 limits the HSPCs to consisting essentially of myeloid hematopoietic progenitor cells that have been genetically engineered to comprise the vector comprising the transgene (e.g., hematopoietic stem cell-derived, myeloid progenitor cells comprising the transgene).
35 USC § 112(a) – Scope of Enablement
Claims 25, 29, 32, and 39 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because while the claims are enabled for a method of treating a cancer or tumor wherein there are sufficient GEMys administered, the mammal is a mouse, and the cancer or tumor is a certain subtype; the specification does not enable any person skilled in the art to which it pertains or with which it is most nearly connected to for performed the claimed methods to treat any connective tissue tumor, kidney tumor, liver tumor, colon or colorectal adenocarcinoma, fibrosarcoma, liver adenocarcinoma, melanoma, pancreatic cancer, primary breast cancer, renal cell carcinoma, or rhabdomyosarcoma in a mouse or human.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). The court in Wands states that "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue.' Not 'experimentation;" (Wands, 8 USPQ2d 104). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighting many factual considerations." (Wands, 8 USPQ2d 1404).
The factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation required is “undue” include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Furthermore, the USPTO does not have laboratory facilities to test if an invention will function as claimed when working examples are not disclosed in the specification. Therefore, enablement issues are raised and discussed based on the state of knowledge pertinent to an art at the time of the invention. And thus, skepticism raised in the enablement rejections are those raised in the art by artisans of expertise.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention:
The claims are directed to methods of treating cancer/tumor in a mouse or human by the step of administering a composition comprising a genetically modified cell population comprising HSPCs and myeloid progenitor cells modified to comprise a vector comprising an IL-12 encoding transgene.
The claims are interpreted as set forth in a previous section. When claims 25, 29, 32, and 39 are analyzed in light of the specification, the instant invention is broadly directed to administering to a mouse or human recipient the recited cell composition of claim 51 specifically comprising a transgene encoding any IL-12 for (1) treating cancer in the recipient, (2) reducing tumor growth in the recipient, (3) extending survival time of a cancer recipient, and/or (4) reducing or preventing metastasis in the recipient wherein the cancer/tumor is selected from any connective tissue tumor, kidney tumor, liver tumor, colon or colorectal adenocarcinoma, fibrosarcoma, liver adenocarcinoma, melanoma, pancreatic cancer, primary breast cancer, renal cell carcinoma, and rhabdomyosarcoma.
Breadth of the claims
The claims are broadly directed to treating any connective tissue tumor, kidney tumor, liver tumor, colon or colorectal adenocarcinoma, fibrosarcoma, liver adenocarcinoma, melanoma, pancreatic cancer, primary breast cancer, renal cell carcinoma, and rhabdomyosarcoma. Further, the instant application defines “treat” broadly to encompass destroying tumor cells, reducing tumor burden, inhibiting tumor growth, reducing the size of a primary tumor, reducing the number of metastatic lesions, increasing survival of the individual, delaying/ inhibiting/ arresting/ preventing the onset or development of metastatic cancer, delaying/arresting primary cancer progression, improving immune responses against the tumor, improving long-term memory immune responses against a tumor antigen, and/or improving the general health of a recipient subject with cancer ([0055]-[0056]).
The claims are also broadly directed to wherein the transgene merely encodes IL-12 but not necessarily expresses IL-12 in the recipient of the administering, such as due to any particular promoter/enhancer setup, e.g., constitutive or conditional. Instead the claims lack any detail on achieving expression and the instant specification merely guides that the vector may optionally include an expression control sequence, such as exemplary promoters ([0037]) amounting merely to express the IL-12 somewhere for an indeterminate amount of time. Thus, the claimed invention is considered for enablement over the scope of wherein no IL-12 expression occurs during the claimed methods.
The level of one of ordinary skill in the art:
The level of skill required to practice all aspects of the invention to its full scope, especially to treat a human patient across the breadth of the claims is high, potentially requiring a medical degree or PhD in a biological/biomedical science.
The state of the art:
The art teaches IL-12 based therapies using cells expressing IL-12, such as mesenchymal stem cells or fibroblasts, including wherein fibroblast based therapy had positive effects for mouse connective tissue tumors (MCA-205) and mouse adenocarcinoma (CT26) but ineffective for mouse adenocarcinomas (MC38 and CT26) in other situations (Nguyen et al., Front Immunol 11: 575597 (2020) at pg. 16, right col., last para., to pg. 17, right col., 3rd para.). The prior art teaches methods of treating tumors and cancers in mammalian subjects comprising administering HSPCs without genetic engineering of any kind, i.e., lacking any IL-12 transgene (hematopoietic stem cell transplantation), such as after chemotherapy for cancer (Dunbar et al., Science 359, eaan4672 (2018), at pg. 1, right col., 2nd para., Fig. 1, Table 1; pg. 6; Naldini, EMBO Mol Med 11: e9958 (2019), IDS ref.; at pg. 1, Fig. 1). The prior art also teaches methods of treating mouse leukemia (e.g., AML or CML) with HSPC GEMys expressing an IL-12 transgene prolonged survival and reduced tumor growth (Gautam et al., Cancer Gene Ther 7: 1060-8 (2000) at Abstract, pg. 1062, left col., last para., to right col., last para; pg. 1065, right col., 2nd para.; Fig. 8). However the prior art is silent as to wherein the cancer is a connective tissue tumor, kidney tumor, liver tumor, colon or colorectal adenocarcinoma, fibrosarcoma, liver adenocarcinoma, melanoma, pancreatic cancer, primary breast cancer, renal cell carcinoma, or rhabdomyosarcoma.
As the prior art does not teach methods of treating any cancer other than acute or chronic myeloid leukemia in a mouse, these aspects must be shown to a reasonable extent so that one of the ordinary skills in the art would be able to practice the invention without any undue burden being on such an Artisan.
The art teaches that preclinical animal models are generally poor predictors of therapeutic or clinical efficacy in humans (Pound and Ritskes-Hoitinga, J Transl Med 16: 304 (2018) at Abstract; pg. 2, left col., 2nd para.; pg. 5, left col., 1st para.), and directs, because of differences between animal and human species, one should first empirically demonstrate, rather than assume, similarity between a model and human disease (id. at pg. 5, left col., 2nd para.). Furthermore, ones of skill in the art would recognize the unpredictability and unreliability in translating treatments in mice cancer models to successfully treat human cancer patients. In particular, animal models using CT26 yield opposite results indicating unpredictability in this field (Nguyen et al., Front Immunol 11: 575597 (2020) at pg. 16, right col., last para., to pg. 17, right col., 3rd para.). In conclusion, animal data (e.g., mouse data) is not predictive for methods of treating human cancer without evidence of clinical predictability, i.e., evidence that animal model data relied upon is predictive for a human subject.
The art teaches pancreatic cancer may be of two major classes that differ significantly from each other: exocrine or neuroendocrine (e.g., PanNETs) (Grant et al., Prog Mol Biol Transl Sci 144: 241-75 (2016) at pg. 2, 2nd para.), mammary cancer may be classified as sarcomatoid or basal-like (e.g., “basal-epithelial phenotype,” “basaloid breast cancer,” or TNBC) (Foulkes et al., N Engl J Med 363(20): 1938-48 (2010) at pg. 1938, para. 2; Lim et al., J Clin Pathol 69(5): 373-81 (2016) at Abstract), and rhabdomyosarcoma may be differential categorized at least as embryonal, alveolar, or pleomorphic (Skapek et al., Nat Rev Dis Primers 5(1): 1 (2020)).
The art teaches while mammalian IL-12s can signal in different species, some IL-12 do not cross reactive across mammalian species, e.g., among human, mouse, sheep, cow , pig, rat, dog , cat and horse (Scheerlinck, Vet Immunol Immunopathol 72: 39-44 (1999) at Table 1). Thus, if the only transgene in the engineered cells consists merely of the transgene encoding IL-12, it would not be predicted to provide any therapeutic effect without expression of an IL-12 protein having function in the mammalian species receiving the administering, as the IL-12 may be any IL-12 from any species, e.g., due to high sequence homology to the endogenous IL-12 of the recipient subject.
The amount of direction and guidance and working examples provided by Applicant:
The instant application provides empirical evidence for treating cancer by delivering exogenous IL-12 via expression from genetically-engineered myeloid cells (GEMys) as shown in mouse models with evidence specifically regarding primary growth of human mammary carcinoma tumors (4T1), metastasis of mouse rhabdomyosarcoma muscle tumors (M3-9-M) to the lung, and metastasis of mouse pancreatic tumor cells (KPC177669) from the spleen to the liver (Examples 3-5, 8, 12 and FIGs. 3-8, particularly FIG. 5F-I). However no direct evidence is provided in the instant application or the prior art regarding using populations of HSPCs comprising GEMys to treat mice or humans for any connective tissue tumor, kidney tumor, liver tumor, colon or colorectal adenocarcinoma, fibrosarcoma, liver adenocarcinoma, melanoma, pancreatic cancer, primary breast cancer, renal cell carcinoma, or rhabdomyosarcoma. Thus, evidence of treatment of a mouse is directly supported for mouse 4T1 mammary ductal adenocarcinomas, mouse M3-9-M embryonal rhabdomyosarcomas, and mouse KPC177669 pancreatic adenocarcinomas depending on the required therapeutic effect.
Regarding claims 25, 29, 32, and 39 the instant specification lacks a working example of any method of treating a mammal beyond treating in mice specific mouse primary mammary tumors that are non-sarcomatoid, mouse rhabdomyosarcoma tumors and cancers that are non-alveolar, and mouse pancreatic tumors and cancers that are non-neuroendocrinal (Examples 2-9; FIG.3-5 and 8).
Regarding claims 25, 29, and 32, the evidence of treating (e.g., by extending survival time or inhibiting tumor growth) in a primary mammary carcinoma (mouse 4T1 ductal adenocarcinoma), rhabdomyosarcoma (mouse M3-9-M embryonal type), or pancreatic (mouse KPC177669 adenocarcinoma) cancer mouse model is not evidence of treating a mouse or human having any connective tissue tumor, kidney tumor, liver tumor, colon or colorectal adenocarcinoma, fibrosarcoma, liver adenocarcinoma, melanoma, pancreatic cancer, primary breast cancer, renal cell carcinoma, or rhabdomyosarcoma. However claims 25, 29, and 32 are supported by evidence specifically wherein the cancer or tumor is a primary mammary ductal carcinoma in a mouse, an embryonal rhabdomyosarcoma in a mouse, or a pancreatic adenocarcinoma in a mouse.
Regarding claim 39, the evidence of inhibiting or preventing metastasis of rhabdomyosarcoma or pancreatic cancer cells is not evidence of reducing or preventing metastasis of any connective tissue tumor, kidney tumor, liver tumor, colon or colorectal adenocarcinoma, fibrosarcoma, liver adenocarcinoma, melanoma, pancreatic cancer, primary breast cancer, renal cell carcinoma, or rhabdomyosarcoma. Claim 39 is supported by direct evidence specifically wherein the cancer is an exocrine pancreatic cancer in a mouse or an embryonal rhabdomyosarcoma in a mouse.
The quantity of experimentation needed to make and/or use the invention:
Extensive experimentation would be required to determine how to treat each condition encompassed by the claims (each individual cancer or tumor type). The science of medicine has not evolved such that, without guidance or working examples in the specification regarding a nexus between expression of the IL-12 transgene in any HSPC population comprising GEMys administered to a mammalian subject and a treating effect for each condition being treated, to enable predictably providing a treatment effect without undue or unreasonable experimentation.
Thus, the skilled artisan cannot envision predictably treating the genus of conditions recited in the claims specifically using IL-12 encoding transgenes across the breadth of the claims, including wherein the mammal is a mouse. The claimed invention as a whole is not adequately described if the claims require essential or critical elements that are not adequately described in the specification and that is not conventional in the art as of applicants effective filing date, such as methods of treating cancer comprising administering HSPCs and/or myeloid progenitor cells expressing IL-12 to a mouse or human having a cancer selected from any connective tissue tumor, kidney tumor, liver tumor, colon or colorectal adenocarcinoma, fibrosarcoma, liver adenocarcinoma, melanoma, pancreatic cancer, primary breast cancer, renal cell carcinoma, and rhabdomyosarcoma. The skilled artisan can envision predictably performing the claimed methods using GEMys expressing a mouse IL-12 in a recipient mouse to treat a primary mammary basal carcinoma, an embryonal rhabdomyosarcoma, a pancreatic adenocarcinoma, or acute/chronic myeloid leukemia.
Therefore, the skilled artisan cannot envision the claimed methods treating the full scope of conditions recited, such as in a human or wherein the pancreatic cancer is neuroendocrine, the primary mammary tumor is a sarcoma, or the rhabdomyosarcoma is alveolar. The specification does not provide any disclosure to what structures or steps provide the recited treating effects across the scope of claimed conditions being treated. Instead, the claims rely on prophetic predictions without providing a sufficient nexus to providing the function of such treating from the limited description of methods using myeloid cells expressing IL-12 from a transgene and the broad genus of cancer conditions in the mouse or human recipient described combined with the knowledge in the prior art as detailed above.
In summary, the claims are rejected under 35 U.S.C. 112(a) because the specification does not reasonably provide enablement, to a person skilled in the art to which it pertains or with which it is most nearly connected to, to perform the claimed invention to treat a mammal having any cancer beyond treating a mouse with a primary mammary basal carcinoma, an embryonal rhabdomyosarcoma, or an exocrine pancreatic adenocarcinoma. Given the lack of working examples, the limited guidance provided in the specification, the lack of guidance in the prior art, and the broad scope of the claims with regard to the diverse conditions being treated, undue and unreasonable experimentation would have been required for one skilled in the art to use the claimed methods to produce the recited result.
Response to Arguments
Applicant's arguments filed 9/2/25 regarding the previous 112(a) rejections (pg. 6-7) have been fully considered but not found persuasive beyond wherein the mammal is a mouse with a primary mammary basal carcinoma, an embryonal rhabdomyosarcoma, or an exocrine pancreatic cancer or tumor.
While enablement of treating a human subject can be demonstrated using solely in vitro or animal testing, in the instant case there needs to be demonstration in the prior art and/or the instant application of a nexus between administering any HSPC population comprising GEMys expressing an IL-12 transgene to a mouse or human with a specific tumor type as providing evidence of a predictably applying a different treatment of another tumor type or providing an different therapeutic effect (reducing or preventing metastasis). Neither the prior art nor the instant application establishes that mouse data solely would apply in a predictable fashion to a human treatment.
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 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.
(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, 4, 7, and 51-52 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gautam (Gautam et al., Cancer Gene Ther 7: 1060-8 (2000)).
The claims are interpreted as provided in a previous section.
Regarding claims 1 and 7, Gautam discloses an HSPC population (32Dc13) transduced to comprise a vector comprising a transgene encoding an IL-12 (Abstract; Fig. 1; Table 1).
Regarding claim 4, Gautam discloses that the vector is a viral vector (retroviral) (Abstract; Fig. 1).
Regarding claim 51, Gautam discloses wherein that the genetically modified cell population comprises GEMys (32Dc13) (pg. 1061, left col., 2nd para.; pg. 1062, right col., 1st para.).
Regarding claim 52, Gautam discloses wherein that the genetically modified HSPC population consists essentially of GEMys (32DIL-12 cells) (Abstract, Table 1 and 3).
Thus, Gautam anticipates the claimed invention.
Claim Rejections - 35 USC § 103
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.
Claims 1-2, 4-5, and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Chmielewski (Chmielewski and Abken, Expert Opin Biol Ther 15: 1145-54 (2015) in view of Vodyanyk (US20180305664A1) and Delaney (US20180355318A1).
The claims are interpreted as set forth in a previous section.
Chmielewski teaches making populations of T cells (TRUCKs) genetically engineered via a viral vector to have a transgene for expression and delivery of an IL-12 cytokine payload in an adoptive cell therapy for treating cancer (Fig. 2; pg. 1147, right col., 1st para., to pg. 1148, left col., 1st para.; pg. 1150, left col., last para., to right col., 1st para.; pg. 1151, right col., 3rd para.; pg. 1146, left col., last para.; pg. 1149, left col., last para., to right col., last para.).
Regarding claims 1 and 7, Chmielewski does not teach wherein the cells are HSPCs. However Vodyanyk teaches obtaining T cells from differentiating in vitro cultured genetically modified HSPCs as a source for mass production of genetically modified T cells for adoptive cell therapies (Abstract, [0043], [0063], [0146], [0160]; Examples 1-4, FIG. 11 and 13). Further, Delaney teaches genetically engineering an HSPC precursor to the T cell instead of performing the engineering after differentiation ([0276], [0055], [0065], [0077]).
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to make an intermediate HSPC population before making the TRUCKs taught by Chmielewski wherein the HSPC are genetically modified to comprise a vector comprising a transgene encoding IL-12 along with a CAR. One of ordinary skill in the art without the goal of providing large numbers of cells of interest for use in an adoptive cell theory would be motivated to first prepare the genetically engineered HSPCs prior to differentiation to form IL-12 expressing TRUCKs as taught by Chmielewski.
Regarding claim 2, Vodyanyk teaches wherein the HSPC population comprises hematopoietic stem cells (HSCs) or hematopoietic precursor cells (HPCs) expressing CD34, such as a marker of lymphoid potential ([0011]; [0086], FIGs. 11, 1C, 3B-C, 4-5; [0041], [063]).
Regarding claims 4-5, Chmielewski teaches genetically engineering the cells using a viral vector which is a lentiviral vector to express IL-12 (pg. 1146, left col., last para.), and also Delany teaches using a lentiviral vector for encoding the CAR ([205]; [0055]).
Thus, the claimed invention as a whole is prima facie obvious prior to the earliest effective filing date in the absence of evidence to the contrary.
Claims 1, 4, 7, 25, 29, 32, 39, and 51-52 are rejected under 35 U.S.C. 103 as being unpatentable over Naldini2 (WO2018193119A1; IDS ref.) in view of Faggioli (Faggioli et al., Breast Cancer Res Treat 110: 223-6 (2008)) and Moyes (Moyes et al., Hum Gene Ther 28: 200-15 (2016); IDS ref.).
Regarding claims 1, 7, and 51, Naldini2 teaches a genetically engineered myeloid progenitor cell (myeloid/monocyte-committed progenitor), and populations thereof, engineered to express cytokines from transgenes (preferably IL-12) for use in treating or preventing a cancer in a patient (claim 1, pg. 22, last para.; pg. 37, 3rd para.; pg. 19, 5th para.). Regarding claim 4, Naldini teaches wherein the vector is preferably a viral vector (pg. 51, 2nd para.).
Regarding claim 25, Naldini2 teaches GEMys engineered to express an IL-12 transgene from a vector for use in treating or preventing a cancer or tumor in a patient (claim 1, pg. 22, last para.; pg. 37, 3rd para.; pg. 19, 5th para.), such as wherein the tumor or cancer is selected from a breast cancer, colon cancer, pancreatic cancer, rabdomyosarcoma, liver cancer, renal cancer, soft tissue sarcoma, or colorectal cancer (claim 10, pg. 22, 5th para.). Naldini2 teaches methods of administering such GEMys comprising a vector comprising a sequence encoding IL-12 to a human or animal (pg. 5, 4th para.; pg. 6, 2nd para.; claims 18-19; pg. 76, last line). However Naldini2 does not expressly teach administering to a mouse or human having breast cancer, a population of cells comprising or consisting of GEMys expressing IL-12.
However Faggioli teaches gene therapy with IL-12 inhibits breast tumor growth and increases survival of a mice model of breast cancer (Fig. 1A, C-D; pg. 223, right col., last para.). Further, Moyes teaches an immunotherapy approach for solid tumors comprising local implantation of human GEMs (monocytes and macrophages) virally engineered to overexpress an immune activating cytokine (IL-21 payload) and with reduced PD-L1 and/or IL-10 expression (pg. 212, 1st para.; Abstract; pg. 213, left col., 2nd para.; Fig. 5E).
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the effective time of filing to select from among the cytokines and cancers taught by Naldini2 to treat breast cancer using an IL-12 transgene in view of Faggioli. Moreover, one of ordinary skill in the art with a goal of applying methods of treating taught by Naldini2 would be motivated to by Moyes to select myeloid precursors cells for administration as a source of IL-12-payload armed monocytes and macrophages in vivo that are engineered to resist tumor secreted suppressive signals (PD-L1 inhibitory signals) and stably secrete immunoactivating cytokine (IL-12), which activates antitumor functions of NK cells, as in Moyes but by selecting IL-12 for breast cancer as already shown to specifically provide benefits in a mouse model of breast cancer as taught by Faggioli.
As previously noted, the intended results recited in the preambles of each of claims 29, 32, and 39 are intended purposes of the claimed methods that do not further limit the method claimed and, thus, carry no patentable weight except requiring the mouse or human of claims 29, 32, or 39 has at least one of the recited cancers and, further for claim 29, must comprise at least one recited tumor. See MPEP 2111. Therefore, the combination of Naldini2, Faggioli and Moyes teaches the methods of claims 29, 32, and 39 for the same reasons as teaching all recited method steps of claim 25 as set forth fully above. Furthermore, Faggioli teaches systemic increase in IL-12 alone is capable of reduced breast tumor growth and extended survival in a mouse model of breast cancer (Fig. 1A, C-D).
Regarding claim 52, Naldini2 teaches wherein the cell population is composed only of myeloid progenitor cells (pg. 22, last para.).
Thus, the claimed invention as a whole is prima facie obvious prior to the earliest effective filing date in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 9/2/25 regarding the previous art rejections (pg. 8-10) have been fully considered and found persuasive; however applicant’s claim amendments resulted in the new grounds of rejection laid out above.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC J ROGERS whose telephone number is (571)272-8338. The examiner can normally be reached Monday - Friday 9:00-6:00.
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/ERIC J ROGERS/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638