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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/19/23 was filed in a timely manner. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
Claim(s) 1-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over the disclosures of Tian Xie et al (Non-invasive monitoring of the kinetic infiltration and therapeutic efficacy of nanoparticle-labeled chimeric antigen receptor T cells in glioblastoma via 7.0 Tesla magnetic resonance imaging, Cytotherapy, 23, 211-222, 2021) in view of Horak et al (WO 2007/095871 A2 hereafter Horak) and Wang et al (Chondroitin sulfate proteoglycan 4 as a target for chimeric antigen receptor-based T-cell immunotherapy of solid tumors, Expert Opinion on Therapeutic Targets, 19:10, 1339-1350, 2015 hereafter Wang).
Tian disclose a method for treating cancer comprising administering a therapeutically effective amount of a T-cell expressing chimeric antigen receptor where the CAR T-cell is loaded with a superparamagnetic iron based particles and is delivered to the tumor [abstract], meeting limitation of claim 1. The loaded CAR T-cell results in a release of cytokines such as TNF alpha, IL-2 and INF gamma [page 213], meeting limitations of claim 2. The CAR T cells are 2nd generation T cells [page 212], meeting limitation of claim 4. The loaded CAR T-cell comprises 50 µg/mL [page 214]. The loaded CAR T-cell is EGFRvIII specific [page 214] meeting limitation of claim 6. The loaded CAR T cell is both diagnostic and therapeutic making it theragnostic [page 212], meeting limitations of claim 7. The superparamagnetic iron based particles can be iron oxide, based and are washed based on a porous membrane filtration [page 212], meeting limitations of claims 8-9, 22. The superparamagnetic iron-based particles are coated with materials like dextran and PLL, an amino acid coating [page 212]. The cells the loaded T cells are applied to are tumors, specifically malignant glioblastoma tumors [page 213], meeting limitations of claim 24. An in vitro method of forming the loaded CAR T cells comprising introducing genetic information into the T cells and loading those cells with superparamagnetic particles [page 212, Methods]. The 2nd generation CAR T cells, further comprise co-stimulatory domains and an intracellular signaling domain including CD28 and CD3ζ [page 214, Results]. The particles are viable via MRI scan [Figure 3], meeting limitations of claims 21.
While the reference discloses a superparamagnetic iron based nanoparticles loaded CAR T cell, where the nanoparticles are coated with amino acid compounds like poly-l-lysine, the reference is silent to specific coatings of claim 23. The use of citrate coating for superparamagnetic iron-based nanoparticles is well known in the art as seen in the Horak patent.
Horak discloses a superparamagnetic iron based nanoparticle that can be attached or uploaded cells for imaging [abstract, page 6, 5-10]. The coatings include amino compounds (page 6, lin. 5-10, page 7, lin. 1-5) along with citrates complexed to the surface of the iron oxide (page. 7, in. 1-20). The coatings allow improved T1 and T2 flexibility of the particles (Example 9). It would have been obvious to include these compounds into the formulation of Xian as they improve the functionality of the loaded T cells.
The combination while disclosing a loaded CAR T cell where the T cells can be EGFRvIII specific, the reference is silent to the specificity of instant claim 20. The use of this specific CAR T cell is known in the art as seen by Wang.
Wang discloses a Chondroitin sulfate proteoglycan 4 target specific T cell for solid tumors [abstract]. The CSPG$ is overexpressed on a wide variety of malignant tumors including renal carcinoma, glioblastoma, head a neck, mesothelioma, and subsets of acute leukemia [4.1]. This Because CSPG4 expresses in so many types of cancers, it would have been obvious to provide this specific binding to the CAR T cells of Xian in order to cover as many conditions in an immunotherapy.
Regarding the reduction of cytokine expression, the Xian discloses that the loaded CAR T cells do not increase of much change the expression of cytokines much when tested. Regardless this claim limitations comes as a feature following the expressed limitations of applying a therapeutically acceptable amount of the loaded CAR T cells to a tumor, which are accomplished by the Xian study. Since the method steps of the instant claims, which comprise the same components and arranged in the same way, for the same purpose, it is the position the Examiner that is feature must also be present.
With these aspects in mind it would have been obvious to combine the prior art with an expected result of a stable method of treating solid tumors. It would have been obvious to include the coatings of Hodak into the method of Xian as they solve the same problem. Further the citrate compound would help increase the flexibility of the paramagnetic iron based particles of Xian as they are the same and solve the same problem of imaging tumors. It would have been obvious to include CSPG4 targeting areas to the CAR T cells as these targets are expressed on a variety of tumors, including glioblastomas, similar to Xian. This would provide a stable formulation possible in treating a variety of cancers in a single immunotherapy. One of ordinary skill in the art would have been motivated to combine these disclosures with an expected result of a stable formulation for targeting and treating solid tumors.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICAH PAUL YOUNG whose telephone number is (571)272-0608. The examiner can normally be reached Monday through Friday, 9:00 am to 5:30 pm.
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/MICAH PAUL YOUNG/ Primary Examiner, Art Unit 1618