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 of Group I (claims 1-8) in the reply filed on 05/11/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 1-13 and 16 are pending; claims 9-13 and 16 are withdrawn from prosecution for being drawn to non-elected inventions. Calims1-8 are examined.
Information Disclosure Statement
The information disclosure statements (IDS)s submitted on 09/13/2024 and 05/30/2025 were 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, they have not been considered.
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.
Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Inoue et al. (Vaccination with irradiated induced pluripotent stem cells genetically engineered to produce GM-CSF confers potent T cells-mediated antitumor immunity. Blood 122 (21), 4492, 2013) in view of Ichim et al. (U.S. Pub. No. 20130273011) and in further view of Tan et al. (The application of exosomes as a nanoscale cancer vaccine, Int. J. Nanomed. 5, 889-900, 2010).
The claims are drawn to a composition comprising a plurality of exosomes generated from stem cells, optionally embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), or a combination thereof, which have been modified to express a granulocyte-macrophage colony stimulating factor (GM-CSF) polypeptide, optionally a mammalian GM-CSF polypeptide. The GM-CSF polypeptide may comprise an amino acid sequence as set forth in SEQ ID NO: 2, and/or is a functional fragment thereof, and/or is at least 95% identical to SEQ ID NO: 2. The composition may further comprise pharmaceutically acceptable carriers and adjuvants.
Inoue et al. disclosed that cancer stem cells (CSCs) shared antigenic similarities with embryonic stem (ES) cells and the vaccination using ES cells could generate antitumor immunity. By forced ectopic expression of defined transcription factors,
autologous somatic cells were successfully reprogrammed into induced pluripotent stem (iPS) cells that closely resemble ESCs. Cell vaccines using mouse iPS cells genetically engineered to express the immunostimulatory cytokine of GM-CSF would cross-react
CSC cells to induce antitumor immunity against poorly immunogenic syngeneic LLC mouse lung cancer cell. Non-transmissible recombinant Sendai virus-mediated mouse GM-CSF gene transferred to iPSCs (iPS/GM-CSF) was effective to produce abundant GM-CSF in vitro and iPS/GMCSF cells maintained their stemness. Prophylactic iPSCs vaccine studies revealed that wild-type female mice subcutaneously vaccinated with irradiated iPS (ir.iPS) cells on weeks 1, 2, and 3 before the tumor challenge with LLC
cells significantly suppressed the LLC tumor growth compared with untreated mice (p<0 .05) . Additionally, mice vaccinated with ir.iPS/GM-CSF cells significantly inhibited the tumor growth compared with mice treated with ir.iPS/GFP cells (p<0.05), showing that genetic manipulation of iPS cells with GM-CSF encoding gene potentiated the antitumor effect. iPS cells-based vaccines effectively generated T cells-mediated antitumor immunity and the authors demonstrated that iPS cells-based vaccine can induce both prophylactic and therapeutic antitumor.
The reference is silent about using exosomes from the stem cells transformed to express GM-CSF.
Ichim et al. disclosed stem cells and nanoparticles derived from said stem cells, useful for the treatment of acute radiation syndrome (ARS) and other inflammatory conditions. Exosomes, nanoparticles that are generated by various stem cells, are used as a drug for treatment of inflammatory conditions (abstract). Methods of isolating exosomes, as well as for analyzing exosomes for activity, are known in the art. One of skill in the art, by using the methods disclosed in the reference, would be able to easily generate therapeutic compositions for treatment ([0014]-[0015].
Tan et al. review the state of the art in vaccines and indicates that the use of nanoscale particles like exosomes in immunotherapy could form a viable basis for the development of novel cancer vaccines, via antigen-presenting cell technology, to prime the immune system to recognize and kill cancer cells. Coupled with nanotechnology,
engineered exosomes are emerging as new and novel avenues for cancer vaccine development some of them in Phase I clinical trial (e.g. exosomes combined with GM-CSF for colorectal cancer) (abstract; Table 1, Figure 1, Table 2).
The vaccination art, at the time that the invention was filed, was mature in using adjuvants in pharmaceutical compositions used for vaccines.
With respect to using the human GM-CSF of SEQ ID NO: 2, as claimed in the claim 5, it is submitted that a person of ordinary skill in the art, when desiring to use an exosome based vaccine for use in human, would necessarily use the human GM-CSF (as having the SEQ ID NO: 2) instead of mouse GM-CSF.
It would have been obvious for a for a person of ordinary skill in the art at the time that the invention was filed to have used the known techniques of obtaining exosomes taught by Ichim et al. and isolate and use exosomes form stem cells expressing GM-CSF with a reasonable expectation of success. This is because the skilled artisan would have used known and tested methods and composition to derive vaccines based on exosomes.
A person of ordinary skill in the art is always motivated to pursue the known options within her or his technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLY GERALD STOICA whose telephone number is (571)272-9941. The examiner can normally be reached M-F 8-5 EST.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647
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