DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-4, 6 and 9-10) in the reply filed on 9/23/2025 is acknowledged. The traversal is on the ground(s) that upon the instant amendment filed 9/23/2025, the shared technical feature among Groups I-III invention is MSCs expressing CXCL9 and at least one of the listed cytokines. This is not found persuasive because MSCs expressing CXCL9 and CD40L, for example, are known at the time of filling according to Lu et al. (WO2018/191619A1). Lu et al. teach that MSCs are engineered to produce CXCL9 (p.26, lines 26-27); or to produce CD40L and CXCL9 (p.32, line 13). The cells are engineered to further produce OX40L (p.32, lines 18-19).
Thus, it would have been obvious to engineer MSCs to express both CXCL9 and OX40L or CD40L as claimed.
Applicant’s election of CXCL9 is acknowledged, however, the species election is withdrawn as CXCL9 is required for claim 1 upon the instant amendment.
The requirement is still deemed proper and is therefore made FINAL.
Claims 11-14 are newly added, claims 5, 7-8 and 13-14 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-4, 6, 9-12 have been considered on the merits.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4, 6 and 9-12 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, 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.
Claim 1 discloses the wherein clause directed to the immunostimulatory factor comprising at least one chemokine, wherein the chemokine comprises CXCL9, and a combination thereof. The limitation discloses only one species belonging to the chemokine. It is not clear then what “a combination thereof” intends to point out. Clarification is required.
Claim 1 discloses the limitation directed to the immunostimulatory factor comprising at least one cytokine, wherein the cytokine comprises: OX40L, 4-1BBL, CITRL, CD40L, and a combination thereof. The limitation (underlined) is not clear if all of the species are required to be expressed by the claimed cell or the species are Markush-type species. In the presence of “a combination thereof” and based on the limitations of claims 2 and 3, it appears that the listed species are alternative each other, however, the claim is written as if all the species are required. Clarification is required. For search purpose, the limitation is interpreted as “the cytokine is selected from the group consisting of OX40L, 4-1BBL, CITRL, CD40L, and a combination thereof”; or use the term “or” instead of “and” at the end.
Claim 4 discloses the types of mesenchymal stem cell. It is not clear if the listed species are all required as the claim utilizes the verb “comprises”, and the term “and” at the end of the listed species. It appears that the limitation is alternative each other. If so, applicant is advised to amend the limitation using “or” instead of “and”.
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 3 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 3 discloses that the immunostimulatory factor is CXCL9 and/or OX40L. However, claim 3 is dependent on claim 1 which discloses that the immunostimulatory factor requires CXCL9 and additional cytokine(s). The limitation of claim 3 does not require CXCL9 as it discloses “or” in the claim. Thus, the limitation of claim 3 does not further limit the subject matter of claim 1.
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.
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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) 1-4 and 11-12 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lu et al. (WO2018191619A1).
Regarding claims 1-4, Lu et al. teach mesenchymal stem cells (MSCs) engineered to express at least one, two, three or more of effector molecules including cytokines and chemokines (p.2, lines 19-22; p.3, lines 15-22). The effector molecules include chemokines and cytokines listed in Table 1 (p.16). Lu et al. teach that MSCs are engineered to produce CXCL9 (p.26, lines 26-27); or to produce CD40L and CXCL9 (p.32, line 13). The cells are engineered to further produce CD40L, OX40L, and/or 41BB-L (p.31, lines 9-11; p.32, lines 18-19). Lu et al. teach that the engineered MSCs are from adipose tissue, i.e. adipose mesenchymal stem cell (p.43, lines 9-11).
Regarding claim 11, the MSCs of Lu et al. are isolated from the body/tissue, e.g. adipose tissue and cultured in vitro, the MSCs of Lu et al. would be ex vivo.
Regarding claim 12 directed to the MSCs being autologous or allogeneic, the wherein clause does not particularly limit the structure of the MSCs, rather the cells being autologous or allogeneic is determined when the cells are utilized in a method. Thus, the wherein clause of claim 12 does not limit the claimed MSCs and claim 12 is interpreted the same as claim 1.
Thus, the reference 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-4, 6, 11-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lu et al. (supra).
Regarding claims 1-4, Lu et al. teach mesenchymal stem cells (MSCs) engineered to express at least one, two, three or more of effector molecules including cytokines and chemokines (p.2, lines 19-22; p.3, lines 15-22). The effector molecules include chemokines and cytokines listed in Table 1 (p.16). Lu et al. teach that MSCs are engineered to produce CXCL9 (p.26, lines 26-27); or to produce CD40L and CXCL9 (p.32, line 13). The cells are engineered to further produce CD40L, OX40L, and/or 41BB-L (p.31, lines 9-11; p.32, lines 18-19). Lu et al. teach that the engineered MSCs are from adipose tissue, i.e. adipose mesenchymal stem cell (p.43, lines 9-11).
Regarding claim 6, Lu et al. teach that the preparation comprising the engineered MSCs can be used to treat cancer and exemplified that the preparation comprising MSCs expressing IL-12 and CCL21 comprises a pharmaceutically acceptable carrier or excipient (p.55, #46). While Lu et al. do not particularly teach that the pharmaceutically acceptable carrier would be used in a preparation comprising MSCs expressing CXCL9 and CD40L, however, it would have been obvious to a person skilled in the art to prepare the engineered MSCs expressing CXCL9 and CD40L with a pharmaceutically acceptable carrier or excipient for their therapeutic use with a reasonable expectation of success.
Regarding claim 11, the MSCs of Lu et al. are isolated from the body/tissue, e.g. adipose tissue and cultured in vitro, the MSCs of Lu et al. would be ex vivo.
Regarding claim 12 directed to the MSCs being autologous or allogeneic, the wherein clause does not particularly limit the structure of the MSCs, rather the cells being autologous or allogeneic is determined when the cells are utilized in a method. Thus, the wherein clause of claim 12 does not limit the claimed MSCs and claim 12 is interpreted the same as claim 1.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 9-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lu et al. as applied to claim 1 above, and further in view of Poznansky (US 2018/0256742).
Regarding claim 9 directed to a medicine kit comprising a first container comprising the MSCs expressing CXCL9 and CD40L/OX40L/4-1BBL/GITRL and a second container comprising an antitumor immunotherapy agent, Lu et al. do not teach the limitation. However, as the engineered MSCs of Lu et al. are intended to treat cancer (i.e. combinatorial cancer immunotherapy), it would have been obvious to use along with another cancer immunotherapy agent(s) known in the art as the chemokine and cytokine expressing engineered MSCs and the cancer immunotherapy agent known in the art are both for the same purpose of treating a cancer (MPEP2144.06(I)). The use of a container in a kit is extremely well known in the art. For example, Poznansky teaches a kit comprising a first container comprising an antibody-antifugetactic agent complex used for treating cancer (para. 27) and a second container comprising an anti-cancer agent such as immunotherapy agent (para. 9 and 23). Thus, it would have been obvious to a person skilled in the art to prepare a kit comprising a first container comprising the engineered MSCs of Lu et al. and a second container comprising anti-cancer agent such as immunotherapy agent as taught by Poznansky with a reasonable expectation of success.
Regarding claim 10 directed to the antitumor immunotherapy agent being an immune checkpoint antibody, Poznansky teaches the immunotherapy agent for treating cancer or tumor is a checkpoint antibody (para. 157-158). It would have been obvious to a person skilled in the art to use immune checkpoint antibody/inhibitor as the immunotherapy agent used along with the engineered MSCs of Lu et al. and thus, prepare the immune checkpoint antibody in the second container of the kit taught by Lu et al. in view of Poznansky.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
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/TAEYOON KIM/ Primary Examiner, Art Unit 1631