DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse of group I, claims 1-2, 4-5, 7-8, 10-16, and 18 in the reply filed on 6/5/26 is acknowledged. Applicant has further elected anti- anti-CD19 as the species of aCAR, an iCAR having one antigen binding domain that is anti-CS1 scFv, and KIR2DL1 as the species of inhibitory and/or co-inhibitory signaling domain. Claims 7 and 15 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to non-elected species.
Claims 1-2, 4-5, 8, 10-14, 16 and 18 are being acted upon.
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) 1-2, 4-5, 8, 10-12, 14, and 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2016/174407 (of record).
WO 2016/174407 teaches a composition comprising an engineered immune effector cell comprising a first and second CAR, wherein each CAR comprises an antigen recognition domain, a spacer, a transmembrane domain, and a endodomain which transmits a signal, and wherein the first CAR is an activator CAR (aCAR) comprising an activating intracellular signaling domain and the second CAR is an inhibitor CAR (iCAR) comprising an inhibitory intracellular signaling domain (see page 11, in particular). WO 2016/174407 teaches NK cell inhibitory signaling domains in the inhibitory CAR, including KIR2DL1, thus meeting the limitations of claims 1, 10-11, and 14 (i.e. an inhibitor signaling domain or a co-inhibitor domain, see pages 37-38, in particular). Regarding claim 2, WO 2016/174407 teaches that the immune cell is a T cell or an NK cell (See page 15, in particular). WO 2016/174407 teaches that the spacer can be an IgG1 hinge (see page 17, in particular). Regarding claim 12, WO 2016/174407 teaches examples wherein the inhibitory intracellular domain and transmembrane domain of the iCAR are from the same molecule (see page 24-25, in particular). Regarding claim 16, WO 2016/174407 teaches that the antigen binding domain of the CAR is an scFV (see page 2, in particular). WO 2016/174407 teaches activation signaling domains comprising CD3 and/or CD28 (see pages 34-35). WO 2016/174407 teaches that leukemia cells can express certain antigens that are also expressed by normal immune cells, and that targeting one antigen alone to treat leukemia will be associated with significant toxicity as it depletes normal cells. WO 2016/174407 explains that the such off target toxicity can be mitigated by using the iCAR (see page 12, in particular). Regarding claim 4 and 8, WO 2016/174407 teaches that particular pairs can be a tumor antigen express by B-CLL (aCAR) and a normal antigen that is an antigen expressed on NK cells (i.e. an antigen binding domain that binds to an antigen on an NK cell, see page 27 Table 6, in particular). As WO 2016/174407 further teaches that the cell co-expressing the first and second CAR can be any of the cells mentioned above, including NK cells (see pages 60-61), the ordinary artisan would at once envisage that the cell expressing the first and second CARs in Table 6 could be an NK cell, thus meeting the limitations of claim 5.
Claim(s) 1-2, 4-5, 8, 10-14, and 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by 20170296623 (of record).
The ‘623 publication teaches a composition comprising an immune effector cell engineered to express at least one N-CAR and at least one P-CAR, wherein the P-CAR binds to a first antigen and actives the immune cell (i.e. an aCAR), and wherein the N-CAR binds to a second antigen and inhibits the immune cells (i.e. an iCAR), see paragraphs 1-2, in particular. The ‘623 publication teaches that the N-CAR and P-CAR each comprise an antigen binding domain, a transmembrane and intracellular signaling domain (see page 3 and 20, in particular). The ‘623 publication teaches that the transmembrane and intracellular domain of the N-CAR are from KIR2DL1 (see pages 21-22 and paragraphs 263, and 785, in particular). The ‘623 publication teaches that the P-CAR comprise a an activating domain and a costimulatory domain (see paragraphs 568-571, in particular). The ‘623 publication teaches that the cell can be a T cell or an NK cell (see paragraph 12-13, 529, and 617, in particular). The ‘632 publication teaches that the N-CAR binds to an antigen expressed in normal tissues but not cancerous tissues, or that is present in normal tissue but down regulated in the tumor of interest and that the P-CAR binds to a cancer antigen (see page 5 and 19, in particular). The ‘623 publication teaches that the N-CAR can target an antigen expressed on natural killer cells, and the ordinary artisan would at once envisage said N-CAR in an NK cell (See page 19, Table, in particular). The ‘623 publication teaches that the antigen binding domain of the CAR is an scFv (see page 5, in particular).
Claim(s) 1-2, 4-5, 8, 10-11, 14, 16 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2019068007.
WO2019068007 teaches a composition comprising engineered immune effector cell comprising an iCAR and an aCAR (see paragraphs 355, 408, exemplary embodimetns and and Fig. 1-2, in particular). WO2019068007 teaches that each CAR comprising an antigen recognition moiety that is an scFV, a transmembrane domain and an intracellular signaling domain (see paragraph 180). WO2019068007 teaches that the immune effector cells is an NK cell and that the iCAR comprising a single transduction element capable of inhibiting the immune effector cells, such as KIR2DL1 (See paragraphs 6, 51 and 148, in particular). WO2019068007 teaches that the aCAR comprises an activation intracellular signaling domain (i.e. endodomain) such as CD3 with or without a costimulatory signaling region (see paragraphs 59-63, in particular). WO2019068007 teaches that the target for the aCAR is a cancer antigen, such as CD19, and the target for the iCAR can be expressed in the same tissues as the aCAR used to treat cancer, but is lost in the tumor cells. WO2019068007 teaches an embodiment wherein the target for the aCAR can be CD19 and the target for the iCAR can be, for example, HLA-A2(i.e. an antigen expressed on NK cells), at once envisage said iCAR in the disclosed immune cells including an NK cell (see paragraph 328). WO2019068007 teaches that the target for the iCAR can be SLAMF7, i.e. CS-1 (See paragraphs 189 and 389, in particular).
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.
Claim 1-2, 4-5, 8, 10-12, 14, 16, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over by WO2019068007 (of record), in view of WO 2016/174407 (of record) and 20170296623 (of record).
The teachings of WO2019068007 are described above. In summary, WO2019068007 teaches an immune effector cell with an iCAR and an aCAR according to claim 1, wherein the iCAR comprises a scFV binds to SLAMF7 (I.e. CS1), a hinge domain, a transmembrane domain, and an inhibitor signaling domain such as from KIR2DL1 (see citations above, and paragraph 151, in particular).
The reference differs from the claimed invention in that it does not explicitly teach that the iCAR comprises an IgG hinge, or a transmembrane domain of KIR2DL1.
The ‘623 publication teaches an immune effector cell engineered to express at least one N-CAR and at least one P-CAR, wherein the P-CAR binds to a first antigen and actives the immune cell (i.e. an aCAR), and wherein the N-CAR binds to a second antigen and inhibits the immune cells (i.e. an iCAR), see paragraphs 1-2, in particular. The ‘623 publication teaches using the transmembrane and intracellular domain from KIR2DL1 in the inhibitory CAR (see pages 21-22 and paragraphs 263, and 785, in particular). The ‘632 publication teaches that when using an inhibitory CAR (N-CAR) the antigen should be expressed in normal tissues but not cancerous tissues, and that antigens present in normal tissue but down regulated in the tumor of interest are suitable for use in an iCAR (see page 5 and 19, in particular).
WO 2016/174407 teaches a composition comprising an engineered immune effector cell comprising a first and second CAR, wherein each CAR comprises an antigen recognition domain, a spacer, a transmembrane domain, and a endodomain which transmits a signal, and wherein the first CAR is an activator CAR (aCAR) comprising an activating intracellular signaling domain and the second CAR is an inhibitor CAR (iCAR) comprising an inhibitory intracellular signaling domain (see page 11, in particular). WO 2016/174407 teaches that the spacer can be an IgG1 hinge (see page 17, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made use KIR2DL1 transmembrane domain, as taught by the ‘623 publication, in the iCAR immune effector cells of WO2019068007. The ordinary artisan at the time the invention was made would have been motivated to do so as a matter of convenience when constructing the modular CAR components (to use both transmembrane and intracellular domain from the same KIR2DL1 receptor, thus decreasing the number of modular components to assemble). Furthermore, it would be obvious to select IgG hinge, as taught by WO 2016/174407, as the hinge in the iCAR of WO 201906807. Doing so would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385). . Regarding claim 5, even though it is anticipated for the reasons set forth above, it would also be obvious to use the NK cell targeting iCAR in an NK cell.
Claim 1-2, 4-5, 8, 10-14, 16, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/174407 (of record), in view of Veillette, 2013 (of record), 20170296623 (of record) and US 2016075784.
The teachings of WO 2016/174407 are described above.
The reference differs from the claimed invention in that it does not explicitly teach that the iCAR binds to CS1, or that the iCAR comprises both transmembrane and signaling domain of KIR2DL1.
Veillette teaches that CS1 is expressed by all NK cells and absent on transformed hematopoietic cells (other than myeloma). Veillette teaches that CS1 is not expressed in transformed hematopoietic types including those where the normal counterpart frequently expresses CS1, indicating that CS1 is lost during malignancy.
The ‘784 publication teaches VH and VL sequences that can be used to generate CS1 targeted CAR.
The ‘623 publication teaches an immune effector cell engineered to express at least one N-CAR and at least one P-CAR, wherein the P-CAR binds to a first antigen and actives the immune cell (i.e. an aCAR), and wherein the N-CAR binds to a second antigen and inhibits the immune cells (i.e. an iCAR), see paragraphs 1-2, in particular. The ‘623 publication teaches using the transmembrane and intracellular domain from KIR2DL1 in the inhibitory CAR (see pages 21-22 and paragraphs 263, and 785, in particular). The ‘632 publication teaches that when using an inhibitory CAR (N-CAR) the antigen should be expressed in normal tissues but not cancerous tissues, and that antigens present in normal tissue but down regulated in the tumor of interest are suitable for use in an iCAR (see page 5 and 19, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made use both transmembrane domain and intracellular domain of KIR2DL1, as taught by the ‘623 publication, in the iCAR immune effector cells of WO 2016/174407. The ordinary artisan at the time the invention was made would have been motivated to do so as a matter of convenience when constructing the modular CAR components. The ordinary artisan would have a reasonable expectation of success, since the references teach that when constructing CAR, one can use the transmembrane domain and intracellular domain from the same receptor, and the ‘623 publication teaches using transmembrane and intracellular domain form KIR2DL1 in particular. Regarding claim 5, even though it is anticipated for the reasons set forth above, it would also be obvious to use the NK cell targeting iCAR in an NK cell.
Regarding claim 18, it would also have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to target CS-1, as taught by Veillette and the ‘784 publication, as the target antigen on NK cells for the iCAR immune effector cells of WO 2016/174407 and the ‘623 publication. The ordinary artisan at the time the invention was made would have been motivated to do so, because WO 2016/174407 and the ‘623 publication teach that the iCAR can target an antigen expressed in normal NK cells but that is down regulated or not expressed in the tumor of interest, and Veillette teaches that CS1 is expressed by all NK cells and absent on most transformed hematopoietic cells where the normal counterpart expresses CS1 since CS1 is lost during malignancy. The ordinary artisan would have a reasonable expectation of success in doing so, since CS-1 VH/VL sequences suitable for use in CAR are known in the art (see the ‘784 publication). Thus, following the teachings of the cited references starting with WO 2016/174407, which teaches an iCAR comprising an scFV that binds an antigen on NK cells, an IgG1 hinge, a transmembrane domain, and an inhibitor signaling domain from KIR2DL1, one would use the transmembrane domain from KIR2DL1, as taught by the ‘623 publication, and would use CS1 as the antigen on NK cells, as taught by Veillette and the ‘784 publication, thus meeting all the limitations of claim 18.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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