DETAILED ACTION
Claims 22-24, 26, and 69-71 from the claim set filed 11/11/2025 are pending. Claims 1-21, 25, and 27-68 are cancelled.
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 .
Election/Restrictions
Applicant’s election without traverse of Group VII, claims 22-24, 26, and 69-71, drawn to a method of reducing the number of tumor cells or cancer burden in a subject in need thereof and/or for treating a subject with cancer or an increased risk of cancer and/or inducing or enhancing an immune response or a memory immune response in a subject, in the reply filed 11/11/2025 is acknowledged. Thus, claims 22-24, 26, and 69-71 will be examined on the merits herein.
Priority
A claim for benefit of a prior-filed application under 35 U.S.C. 119(a)-(f) or under 35
U.S.C. 120, 121, 365(a)-(c), 386 (a) or 386(c) has been made. The effective filing date of the
present application is 5/26/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/23/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or listed on the submitted IDS(s), they have not been considered.
Double Patenting
Claims 22-23 and 70-71 are rejected on the grounds of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 10,022,405 in view of Lu (WO 2020081869 A1, published April 23, 2020; PTO 892). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-4 of U.S. Patent No. 10,022,405, in view of Lu, make obvious claims 22-23 and 70-71 of the instant application.
Instant Application
Claim 22: A method of reducing the number of tumor cells or cancer burden in a subject in need thereof and/or for treating a subject with cancer or an increased risk of cancer and/or inducing or enhancing an immune response or a memory immune response in a subject, optionally with cancer or an increased risk of cancer, comprising administering to the subject one or more vector constructs, an isolated virus, an isolated cell, a transduced cell, a population of cells, a whole cell vaccine or a composition, wherein
a) the one or more vector constructs comprise:
a lentiviral vector;
an IL-12 expression cassette; and
an IL-21 expression cassette and/or an IL-18 expression cassette;
wherein the IL-12 expression cassette, and the IL-21 expression cassette and/or the IL- 18 expression cassette are in separate expression vector constructs or in a single expression vector construct,
b) the isolated virus comprises the vector construct of a),
c) the isolated cell or transduced cell secretes IL-12 and at least one of IL-18 and/or IL-21 at the or above a threshold level,
d) the population of cells comprises at least 0.1 to 50% of the isolated cell or transduced cell of c),
e) the whole cell vaccine comprises the isolated cell or transduced cell of c) or the population of cells of d), or
f) the composition comprises the vector construct, the isolated virus, the isolated cell, the transduced cell, the population of cells, or the whole cell vaccine.
Claim 23: The method of claim 22 for treating a subject with cancer or an increased risk of cancer, wherein the cancer is leukemia, preferably ALL, AML, CML or CLL, lymphoma, myeloma, glioblastoma, melanoma, or cancer of the lung, ovary, prostate, breast, colon, bladder, liver, pancreas, thyroid, or head and neck.
Claim 70: The method of claim 22, wherein:
A) the IL-12 expression cassette and the IL-21 expression cassette and/or IL-18 expression cassette are in separate expression vectors; the IL-21 expression cassette and the IL-12 expression cassette form an IL-12-IL- 21 expression cassette or IL-21-IL-12 expression cassette; or the IL-18 expression cassette and the IL-12 expression cassette form an IL-12-IL- 18 expression cassette or IL-18-IL-12 expression cassette;
B) the virus is a lentivirus or adenovirus or adeno associated virus;
C) the isolated cell is transduced with the vector construct of a) or the isolated virus of b);
D) the population of cells comprises at least 0.5% to about 40%, about 0.5%, about 1%, about 1-5%, 5-10%, 10-40% or more isolated cells or transduced cells of c), and wherein the population of cells secretes IL-12 and at least one of IL-18 and/or IL-21 above a threshold level, optionally at a level to induce or enhance an immune response, preferably a CD4+ T cell dependent immune response,
E) the whole cell vaccine of e) further comprises an adjuvant, or
F) the composition of f) is a pharmaceutical composition and further comprises a pharmaceutically acceptable carrier.
Claim 71: The method of claim 22, wherein:
i) the transduced cell is produced by a method of expressing IL-12 and at least one of IL-18 and/or IL-21 in a cell, optionally a cancer cell, comprising contacting the cell with the composition, the vector construct, or the isolated virus under conditions that permit transduction of the cell, thereby providing a transduced cell, wherein the IL-12, IL-18, and/or IL-21 is secreted;
ii) the number of cells or population of cells ranges from 105 cells to 109 cells, preferably about 105 cells, about 106 cells, about 107, cells, about 108 cells, or about 109 cells;
iii) the transduced cell, the population of cells or composition is growth arrested or irradiated and introduced in a subject; and/or
iv) the transduced cell is a cancer cell, preferably derived from the subject with cancer, optionally wherein the cancer cell is a leukemic cell, preferably an ALL cell, an AML cell or a CLL cell, lymphoma cell, myeloma cell, glioblastoma cell, melanoma cell, or cancer cell of the lung, ovary, prostate, breast, colon, bladder, liver, pancreas, thyroid, or head and neck.
U.S. Patent No. 10,022,405
Claim 1: A method of treating cancer in a human patient in need thereof, the method comprising administering to the patient a composition comprising a population of human cells transduced with a retroviral vector comprising a polynucleotide encoding human interleukin-12 (IL-12), wherein the population of cells secretes IL-12 at a concentration of at least about 1,500 pg/ml when the cells are cultured at a density of about 106 cells/ml for 2 hours.
Claim 2: The method of claim 1, wherein the cells are cancer cells.
Claim 3: The method of claim 2, wherein the cancer cells are leukemia cells.
Claim 4: The method of claim 3, wherein the leukemia cells are acute myeloid leukemia (AML) cells, acute lymphoid leukemia (ALL) cells, chronic myeloid leukemia (CML) cells, or chronic lymphoid leukemia (CLL) cells.
Claims 1-4 of ‘405 make obvious claims 22-23 and 70-71 of the instant application, in view of Lu, as discussed below.
Claims 1-4 of ‘405 differ from the instant application in that the claims of ‘405 are written in a more concise manner. Ultimately, claim 1 of ‘405 teaches a method of treating cancer in a subject, as does the instant application claim 22. Further, claim 1 of ‘405 teaches administering to the subject a population of cells transduced with a retroviral vector comprising IL12. Instant claim 22 teaches administering to a subject a population of cells secreting IL12 as well as administering a lentiviral vector comprising IL12.
The difference between claims 1-4 of ‘405 and instant claims 22-23 and 70-71 is that ‘405 does not teach of IL21 and/or IL18. However, as will be discussed below, the teachings of Lu make obvious the inclusion of IL21 with IL12.
In regards to the other claim language listed in instant claim 22, said claim language is superfluous as the claim language includes the use of “and/or”.
Lu teaches a multicytokine lentiviral vector comprising an IL-12 expression cassette and an IL-21 expression cassette for engineering human MSCs to overexpress IL12 and IL21 (Example 19, p178) for use in treating cancer (Examples 26-28).
Lu teaches in Example 19 (p178) of engineering human MSCs to produce IL12 and IL21. Lu teaches of using lentiviral transduction (i.e., a lentiviral vector) and teaches various constructs were tested with different combinations and/or arrangements of the IL12 and IL21 expression constructs (see Table 7, p178; Table 8, p179). Thus, Lu teaches wherein the IL12 and the IL21 expression cassettes are in a single expression vector construct.
Lu teaches SB00880 (Table 8, p179) demonstrated expression of both cytokines by engineered MSCs at higher levels than the majority of constructs tested (p183). Additionally, the ratio of IL12 to IL21 was determined (Fig 47). Lu teaches MSCs engineered using SB00880 demonstrated a 10 fold higher ratio of IL12 relative to IL21 and further notes a ratio of 10:1 has demonstrated pre-clinical efficacy (p184).
Lu additionally teaches that MSCs producing both IL12 and IL21 reduce tumor burden in a CT26 IP tumor model, a B16F10 IP tumor model, and a MC-38 IP tumor model (Examples 26-28, p188-190). Lu teaches (Example 28) of mice being treated with different amounts of the engineered MSCs ranging from 3x10^4 to 1x10^6 cells. Lu teaches anti-tumor activity was observed in a dose-dependent manner of MSCs expressing both IL12 and IL21 (p190).
Thus, Lu teaches a method of reducing the number of tumor cells or cancer burden in a subject in need thereof and/or treating a subject with cancer and/or inducing an immune response in a subject with cancer, comprising administering to the subject one or more vector constructs wherein the one or more vector constructs comprise a lentiviral vector; an IL12 expression cassette; and an IL21 expression cassette; wherein the IL12 expression cassette and the IL21 expression cassette are in a single expression vector construct.
Therefore, it would have been obvious, to one of ordinary skill in the art before the effective filing date of the claimed invention, to combine the teachings of Lu and ‘405 in order to have a method for treating a subject with cancer via administering a population of cells expressing IL12 and IL21 via a vector construct. A POSITA would have been so motivated and have a reasonable expectation of success due to both ‘405 and Lu studying cytokine expression as a form of cancer treatment.
Further, in regards to claim 70, Lu teaches at least of (a) the IL 21 and the IL12 expression cassette form an IL12-IL21 expression cassette (Table 7, p178); (b) the virus is a lentivirus (lines 21-25, p32); and (c) the isolated cell is transduced with the vector construct of a) or the isolated virus of b) (Example 6, p172).
In regards to claim 71, Lu teaches a transduced cell produced by a method of expressing IL12 and IL21 in cancer cell, comprising contacting the cells with the vector construct that permits transduction of the cell, thereby providing a transduced cell wherein IL12 and IL21 is secreted. Lu teaches the cell secretes the effector molecules (i.e., IL12 and IL21) (p31, lines 19-21). Thus, Lu teaches i) .
Thus, claims 1-4 of ‘405, in view of Lu, make obvious claims 22-23 and 70-71.
The nonstatutory obviousness-type double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory obviousness-type double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory obviousness-type double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plainest meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claims 22, 70, and 71 use the term “optionally” and claims 23, 26, 70, and 71 use the term “preferably”. Examiner notes that said terms do not further limit claims 22, 23, 26, and 70-71.
Thus, claim 22: “A method of … inducing or enhancing an immune response or a memory immune response in a subject, optionally with cancer or an increased risk of cancer…” is not further limited by the phrase “optionally with cancer or an increased risk of cancer…”.
Claim 23: “wherein the cancer is leukemia, preferably ALL, AML, CML, or CLL,” is not further limited by the phrase “preferably ALL, AML, CML, or CLL,”.
Claim 26: “against a leukemia, preferably ALL, AML, CML, or CLL,” is not further limited by the phrase “preferably ALL, AML, CML, or CLL,”.
Claim 70: “wherein the population of cells secretes IL-12 and at least one of IL-18 and/or IL-21 above a threshold level, optionally at a level to induce or enhance an immune response, preferably a CD4+ T cell dependent immune response” is not further limited by the phrases “optionally at a level to induce or enhance an immune response, preferably a CD4+ T cell dependent immune response”.
Claim 71: “i) the transduced cell is produced by a method of expressing IL-12 and at least one of IL-18 and/or IL-21 in a cell, optionally a cancer cell …. iv) the transduced cell is a cancer cell, preferably derived from the subject with cancer, optionally wherein the cancer cell is a leukemic cell, preferably an ALL cell, an AML cell or a CLL cell, lymphoma cell, myeloma cell, glioblastoma cell, melanoma cell, or cancer cell of the lung, ovary, prostate, breast, colon, bladder, liver, pancreas, thyroid, or head and neck” is not further limited but the incorporation of the “optionally” and “preferably” phrases.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claim 22 and dependent claims 23-24, 26, and 69-71 are rejected under 35 U.S.C. 112(a), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, at the time the application was filed, had possession of the claimed invention. Dependent claims 23-24, 26, and 69-71 are rejected by virtue of their dependency on claim 22 and for not remedying the issue at hand.
In regards to claim 22, the claim language as currently written requires:
A method:
of reducing the number of tumor cells or cancer burden in a subject in need thereof; and/or
for treating a subject with cancer or an increased risk of cancer; and/or
inducing or enhancing an immune response or a memory immune response in a subject, optionally with cancer or an increased risk of cancer,
comprising administering to the subject:
one or more vector constructs;
an isolated virus;
an isolated cell;
a transduced cell;
a population of cells;
a whole cell vaccine; or
a composition,
wherein:
the one or more vector constructs comprise:
a lentiviral vector;
an IL-12 expression cassette; and
an IL-21 expression cassette and/or an IL-18 expression cassette;
wherein the IL-12 expression cassette, and the IL-21 expression cassette and/or the IL- 18 expression cassette are in separate expression vector constructs or in a single expression vector construct;
the isolated virus comprises the vector construct of a);
the isolated cell or transduced cell secretes IL-12 and at least one of IL-18 and/or IL-21 at the or above a threshold level;
the population of cells comprises at least 0.1 to 50% of the isolated cell or transduced cell of c);
the whole cell vaccine comprises the isolated cell or transduced cell of c) or the population of cells of d); or
the composition comprises the vector construct, the isolated virus, the isolated cell, the transduced cell, the population of cells, or the whole cell vaccine.
To satisfy the written description aspect of 35 U.S.C. 112, first paragraph, Applicants must show that they are in possession of the invention being claimed. Possession of an invention may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings, structural chemical formulas or sequences that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998).
The application is considered to lack written description for the full genus of the above written method.
Issues in regards to the method claimed:
In regards to the claimed method, a review of the specification shows Applicant does not provide sufficient written description for:
A method:
of reducing the number of tumor cells or cancer burden in a subject in need thereof; and/or
for treating a subject with cancer or an increased risk of cancer; and/or
inducing or enhancing an immune response or a memory immune response in a subject, optionally with cancer or an increased risk of cancer,
Examiner notes the scope of the claimed method is overly broad. The application contains written description, in the form of proof-of-concept (Figures 1-5), to the single species of a method for treating a subject with leukemia. Examiner notes IL-12, IL-21 and IL-18 have been studied in regards to their therapeutic effects on different types of cancer. However, Applicant is claiming a very broad genus of method and such a broad genus needs sufficient written description to show Applicant is in possession of the genus claimed.
Applicant has not provided sufficient written description for the claimed method. Applicant has provided data showing an increase in survival in a murine leukemia model when mice are transduced with either LV12:LV21 or LV12:LV18. Applicant has not provided data that the claimed method reduces the number of tumor cells or cancer burden in ANY subject in need (e.g., a subject with glioblastoma multiform, pancreatic cancer, melanoma, etc), nor does Applicant provide data for treating ANY subject with an increased risk of cancer (i.e., said subject does not currently have cancer), nor does Applicant provide data showing an induced or enhanced immune response or a memory immune response in ANY subject either with or without cancer. Due to the prior art teaching (as noted in the instant specification [0012]) that combining cytokines (i.e., IL-12 and IL-18) can cause a toxic effect, Examiner notes Applicant needs to provide more data in regards to the claimed method in order to be considered to have sufficient written description.
Thus, Applicant has not disclosed a representative number of species within the claimed genus to demonstrate Applicants were in possession of the full genus as claimed. The data provided in Figures 1-5 are not representative of the broad genus claimed.
Issues in regards to administering to the subject:
In regards to the claimed administering, a review of the specification shows Applicant has not provided sufficient written description for the claimed genus of: administering to the subject, in ANY amount and through ANY route of administration. As noted in the instant specification ([0017], [0018]), low levels of IL-12 may not be recognized and as such there must be a certain level of the second cytokine being administered. Examiner notes:
(a) there is not a specified amount of the vector construct to be administered
(b) there is not a specified amount of the isolated virus comprising the vector construct to be administered
(c ) there is not a specified amount of the isolated cell or transduced cell to be administered as well as there not being a specified threshold level of secretion of IL-12 and at least one of IL-18 and/or IL-21
(d) there is not a specified amount of the population of cells to be administered
(e ) there is not a specified amount of the whole cell vaccine to be administered
(f) there is not a specified amount of the composition to be administered.
Applicants have not disclosed a representative number of species within the claimed genus to demonstrate that Applicants were in possession of the full genus as claimed. The application contains written description, via proof of concept (Figures 1-5) to support administering a therapeutically effective amount of LV12:LV21 or LV12:LV18 via injection.
Accordingly, said claims are considered to lack sufficient written description and are properly rejected.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 22 and dependent claims 23-24, 26, and 70-71 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
In regards to claim 22, the phrase “threshold level” is a relative term which renders the claim indefinite. The term “threshold level” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Examiner notes the specification teaches: [00181] “In one aspect, methods for expressing IL-12 and one or more of IL-21 or IL-18 in cells above a threshold level, within a selected range or at a selected ratio are provided. For example, the threshold level, range and/or ratio can be determined by identifying the level of expression that for the cytokine of interest (e.g. IL -12) produces an incomplete immunity when administered to mice at a 1:10 ratio with untransduced cells but produces complete immunity when administered at 10% when further expressing either IL-21 or IL-18 as described in the examples.” Additionally, the specification teaches: [00311] “and analyzed for the required level of expression (e.g., above a threshold level, within a selected range and/or at a selected ratio)”. However, Applicant has not stated what the specific range and/or ratio of expression is required for said “threshold level” and thus the metes and bounds of the claim cannot be determined.
The claims are considered indefinite because there is a question or doubt as to how to quantitatively measure the “threshold level”.
Thus, the claims are properly rejected.
Claim Rejections - 35 USC § 102
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 22-24, 26, and 69-71 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lu (WO 2020081869 A1, published April 23, 2020; PTO 892).
In regards to claim 22, Lu teaches a multicytokine lentiviral vector comprising an IL-12 expression cassette and an IL-21 expression cassette for engineering human MSCs to overexpress IL12 and IL21 (Example 19, p178) for use in treating cancer (Examples 26-28).
Lu teaches in Example 19 (p178) of engineering human MSCs to produce IL12 and IL21. Lu teaches of using lentiviral transduction (i.e., a lentiviral vector) and teaches various constructs were tested with different combinations and/or arrangements of the IL12 and IL21 expression constructs (see Table 7, p178; Table 8, p179). Thus, Lu teaches wherein the IL12 and the IL21 expression cassettes are in a single expression vector construct.
Lu teaches SB00880 (Table 8, p179) demonstrated expression of both cytokines by engineered MSCs at higher levels than the majority of constructs tested (p183). Additionally, the ratio of IL12 to IL21 was determined (Fig 47). Lu teaches MSCs engineered using SB00880 demonstrated a 10 fold higher ratio of IL12 relative to IL21 and further notes a ratio of 10:1 has demonstrated pre-clinical efficacy (p184).
Lu additionally teaches of MSCs producing both IL12 and IL21 reduce tumor burden in a CT26 IP tumor model, a B16F10 IP tumor model, and a MC-38 IP tumor model (Examples 26-28, p188-190). Lu teaches (Example 28) of mice being treated with different amounts of the engineered MSCs ranging from 3x10^4 to 1x10^6 cells. Lu teaches anti-tumor activity was observed in a dose-dependent manner of MSCs expressing both IL12 and IL21 (p190).
Thus, Lu anticipates claim 22 in at least that Lu teaches a method of reducing the number of tumor cells or cancer burden in a subject in need thereof and/or treating a subject with cancer and/or inducing an immune response in a subject with cancer, comprising administering to the subject one or more vector constructs wherein the one or more vector constructs comprise a lentiviral vector; an IL12 expression cassette; and an IL21 expression cassette; wherein the IL12 expression cassette and the IL21 expression cassette are in a single expression vector construct.
Thus, the claim is anticipated and is properly rejected.
In regards to claim 23, Lu teaches the method of claim 22 and further teaches the tumor is selected from the group consisting of: an adenocarcinoma, an acute myeloid leukemia (AML), an acute lymphoblastic B-cell leukemia (BALL), an acute lymphoblastic T-cell leukemia (TALL), a B-cell prolymphocytic leukemia, a bladder tumor, a brain tumor, a breast tumor, a cervical tumor, a chronic lymphocytic leukemia, a chronic myeloid leukemia (CML), a colorectal tumor, an esophageal tumor, a glioma, a kidney tumor, a liver tumor, a lung tumor, a lymphoma, a melanoma, a mesothelioma, a myelodysplasia, an ovarian tumor, a pancreatic tumor, a plasma cell myeloma, a prostate tumor, a skin tumor, a thyroid tumor, and a uterine tumor. In some aspects, the tumor is an ovarian tumor (p35-36).
Thus, the claim is anticipated and is properly rejected.
In regards to claim 24, Lu teaches the method of claim 23 and further teaches monitoring of cancer progression. Lu teaches of measuring the tumor burden by tumor weight at day 7 post treatment of MSC treated mice, engineered to express both IL12 and IL21, and further teaches mice were euthanized when reaching endpoint criteria due to tumor burden. As shown in Fig 64A, mice treated with said MSCs outperformed recombinant cytokine therapy as assessed by tumor weight. Additionally, as shown in Fig 64B, mice treated with said MSCs outperformed recombinant cytokine therapy as assessed by tumor-free prolonged survival (Example 32, p193-194). This reads on “monitoring cancer progression.”
Thus, the claim is anticipated and is properly rejected.
In regards to claim 26, Lu teaches the method of claim 22. Lu further teaches a method of stimulating a cell-mediated immune response to a tumor cell in a subject, the method comprising administering to a subject having a tumor a therapeutically effective dose of any of the engineered cells or the population of cells described herein (lines 1-5, p17). As noted above in regards to claim 23, Lu teaches said tumor cells may be selected from the group consisting of: an adenocarcinoma, an acute myeloid leukemia (AML), an acute lymphoblastic B-cell leukemia (BALL), an acute lymphoblastic T-cell leukemia (TALL), a B-cell prolymphocytic leukemia, a bladder tumor, a brain tumor, a breast tumor, a cervical tumor, a chronic lymphocytic leukemia, a chronic myeloid leukemia (CML), a colorectal tumor, an esophageal tumor, a glioma, a kidney tumor, a liver tumor, a lung tumor, a lymphoma, a melanoma, a mesothelioma, a myelodysplasia, an ovarian tumor, a pancreatic tumor, a plasma cell myeloma, a prostate tumor, a skin tumor, a thyroid tumor, and a uterine tumor. In some aspects, the tumor is an ovarian tumor (p35-36).
Thus, the claim is anticipated and is properly rejected.
In regards to claim 69, Lu teaches the method of claim 22. Further, Lu teaches MSCs engineered using SB00880 (i.e., the transduced cells) demonstrated a 10 fold higher ratio of IL12 relative to IL21 and further notes a ratio of 10:1 has demonstrated pre-clinical efficacy (p184).
Thus, the claim is anticipated and is properly rejected.
In regards to claim 70, Lu teaches the method of claim 22 and further teaches at least of (a) the IL 21 and the IL12 expression cassette form an IL12-IL21 expression cassette (Table 7, p178); (b) the virus is a lentivirus (lines 21-25, p32); and (c) the isolated cell is transduced with the vector construct of a) or the isolated virus of b) (Example 6, p172).
Thus, the claim is anticipated and is properly rejected.
In regards to claim 71, Lu teaches the method of claim 22. As noted in the above discussed claims, Lu teaches a transduced cell produced by a method of expressing IL12 and IL21 in cancer cell, comprising contacting the cells with the vector construct that permits transduction of the cell, thereby providing a transduced cell wherein IL12 and IL21 is secreted. Lu teaches the cell secretes the effector molecules (i.e., IL12 and IL21) (p31, lines 19-21). Thus, Lu teaches i).
Thus, the claim is anticipated and is properly rejected.
Prior Art Made of Record
Examiner wishes to note the following prior art which relates to the instant application but has not been applied:
Medin (EP 3293266 A1, published March 14, 2018; PTO 892)
Medin ‘266 teaches of IL12 for immunotherapy for cancer. Medin ‘266 teaches of compositions and methods for delivering immune modulatory molecules to result in a therapeutic effect. Medin teaches the compositions and methods use stably integrating lentiviral delivery systems. The methods are useful for therapeutically and prophylactically treating cancer such as leukemia (Abstract). Medin ‘266 further notes IL-18 is a useful immune modulatory molecule for promoting anti-tumor effects and would be suitable for use in the constructs of the present application [0099].
Zhang (WO 2018/184484 A1, published November 10, 2018; PTO 892)
Zhang teaches of a cytokine combination for treating a tumor and/or preventing recurrence or metastasis of the tumor. The cytokine combination comprises at least 3 cytokines. The cytokines are selected from the following groups: an IL12 or a functional variant thereof, … an IL21 or a functional variant thereof… Also provided is a nucleic acid molecule encoding the cytokine combination and a vector thereof, a cell, a pharmaceutical composition, and a use thereof for the manufacture of a medicament for treating the tumor and/or preventing recurrence or metastasis of the tumor (Abstract).
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE R SMALL whose telephone number is (703)756-4783. The examiner can normally be reached Monday - Friday 8:30am-4pm.
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/KATHERINE R SMALL/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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