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 1-16, 18-19, 23, 28, 30-31, 35, and 39, in the reply filed on 2/10/26, is acknowledged.
Applicant has further elected, with traverse, Treg as the species of CD4 T cell, CD62L+CD44+ naïve as the species of phenotype, and cancer as the species of disease. Applicant's traversal is on the grounds that it would not be an undue burden to examine all of the species. Even though examination all of the species would be a burden (since it would require searching for structurally and functionally distinct cell types with different methods steps for their production and different diseases with distinct etiologies and pathological mechanism), Applicant’s augment is not found persuasive because undue burden is irrelevant to the restriction practice for cases filed under 35 U.S.C 371 (see MPEP Chapter 1800).
The requirement is still deemed proper and is therefore made FINAL.
Claims 36-38 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Claims 7-9, 12, 18, 28, 30-31, 35 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 1-6, 10-11, 13-16, 19, 23, and 39 are being acted upon.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 39 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 39 depends from claim 36, which is directed to a pharmaceutic composition comprising a cell produced by the method of claim 1. However, the patentability of a product does not depend on its method of production. In other words, the process steps of claim 1 are not required elements in claim 36, since the claim could be infringed by a structurally identical cell produced by a different process. Therefore, claim 36 does not induce all the limitations of the claim upon which it depends. As claim 39 depends from claim 36, it similarly does not include all the limitations of claim 1 from which it ultimately depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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(s) 1, 10-11, 13-16, 19, 23, and 39 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over WO 2017/127755.
WO 2017/127755 teaches a method of improving therapeutic potential of a T cell population by contacting the T cells in vitro or ex vivo with an agent from Table 1, wherein Table 1 discloses a MEK inhibitor (See pages 4-5, 7, and 47 in particular). WO 2017/127755 teaches that the T cells can be CD4+ T cells (see page 23, in particular). See also Table 1-2 and paragraph 131, wherein WO 2017/127755 discloses MEK inhibitor U0136 is disclosed as a modulator for CD4 T cells, in particular. Thus, the ordinary artisan would at once envisage that the MEK inhibitors are contemplated to be used for contacting CD4+ T cells. Alternatively, it would be obvious to use the MEK inhibiters for CD-4+ T cells based on the above teachings.
WO 2017/127755 also teaches that the method increases stem cell memory T cells (see page 46, in particular). WO 2017/127755 teaches that the methods increase cell potency and de-differentiation, with increased plasticity to differentiate into more cell types, i.e. multipotency (see paragraph 49 and102, in particular). WO 2017/127755 teaches that the T cells can express can exogenous nucleic acid encoding a CAR (see page 8 and 76, in particular). WO 2017/127755 teaches that the T cells have increased expression of CD62L (see page 14, in particular). WO 2017/127755 teaches that the MEK inhibitors include AZD6244, i.e. Selumetinib, see page 38, in particular. WO 2017/127755 teaches that the T cells can be expanded with anti-CD3 and anti-CD28 (see page 49, in particular). WO 2017/127755 teaches that the T cells can be used to treat cancer (see page 61 and 761-, in particular). WO 2017/127755 teaches that the T cell composition can further comprise one or more additional agents such as a immunomodulatory drug or chemotherapy (i.e. second therapeutic agent), and that the method of treatment can comprise administering said T cells and said immunomodulatory drugs or chemotherapy (See paragraph 36 and 198, in particular). Regarding the recitation of a CD62L+CD44+ phenotype, this would be an inherent or latent property of contacting CD4 T cells with a MEK inhibitor.
Claim(s) 1-6 and 11 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by Gabrysova, 2011, as evidenced by Kleinewietfeld, 2013.
Gabrysova teaches a method comprising culturing CD4+ T cells in vitro with an effective amount of MEK1/2 inhibitor PD0325901 (see Fig 3, in particular). Gabrysova teaches that the T cells are also cultured concurrently under Treg inducing conditions that include culture with IL-2 and TGF-beta for 7 days (see page 4296, in particular). Gabrysova teach that the cells are expanded with atni-CD3 and anti-CD28 (see page Fig 3 and 1246, in particular). The method is identical to that of the instant claims, and it would inherently produce CD4 T stem cell like memory CD44+CD62L+ T cells. . Regarding the limitation that the cells are multipotent, it is noted that the specification discloses that this encompass cells that are able to generate other CD4 T cell phenotypes after activation. As evidenced by Kleinewietfeld, T cells and Tregs are inherently “multipotent” in that they have plasticity to differentiate into other phenotypes after activation, such as Th1 and TH17 cells. Regarding the remaining limitations of claim 4-6, it is noted that the claims recite no limitations regarding multiple steps or that differentiation conditions are performed subsequent to contact with the MEK inhibitor. Thus, claims 4-6 would appear to encompass the concurrent 7 day culture performed by Gabrysova. For example, the instant specification teaches that MEK inhibitors induce a stem cell like phenotype within 72 hours, and therefore the 7 day cultures of Gabrysova would inherently induce stem cell-like memory phenotypic cells that would be contacted with the differentiation inducing conditions for Treg differentiation during the remaining 4 days of the culture.
Claim 1, 4-6, 10-11, 13-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/127755, in view of WO2008/095141 and Davidson, 2007.
The teachings of WO 2017/127755 are described above. To summarize, WO 2017/127755 teaches producing CAR modified T cells, such as CD4+ T cells, wherein the cells are treated with various agents from Table 1, such as MEK inhibitors, to increase therapeutic potential of the T cells. The method of WO 2017/127755 is exemplified in Examples 13-14 wherein the reference discloses a process wherein CAR transduction procedure involves culture and expansion with the agent from Table 1 to provide for CAR CD4+ T cells with the improved properties.
The reference differs from the claimed invention in that it does not explicitly teach further contacting with Treg inducing conditions.
WO2008/095141 teaches that CD4+ Tregs can be engineered to express a CAR for redirecting the Tregs toward a desired antigen, and that the Tregs can be provided by introducing a CAR into (non-Treg) T cells, and thereafter inducing the T cells to differentiate into a Treg phenotype by exposure to TGF-beta (see page 18, in particular).
Davidson teaches that IL-2 is essential for TGF-beta mediated induction of Tregs and enhances Treg induction.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to further differentiate the CAR modified, MEK induced CD4 T cells taught by WO 2017/127755, to a Treg phenotype as taught by WO2008/095141. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because WO2008/095141 teaches that after transducing T cells to express a CAR, they can be induced to differentiate into CD4+ Tregs by culturing with TGF-beta, and that doing so can advantageously provide a CD4+ Treg redirected toward a desired antigen. It would also be obvious to include IL-2 in the Treg inducing cultures, since Davidson teaches that it is essential for TGF-beta mediated induction of Treg and enhances Treg induction.
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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