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 .
Claim Objections
Claim 15 is objected to because of the following informalities: please use the Greek character for interferon-γ, both claims 22 and 23 utilize Greek characters, and in order to maintain consistency with the claim-set, claim 15 should provide for the character γ (gamma). Appropriate correction is required.
Claim Rejections - 35 USC § 102/103
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.
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.
Claims 11-13, 16-19 and 21-24 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 Klingemann, et al (Cytotherapy, 6, 15-22, 2004) and evidenced by Abbassi, et al (International Journal of Hematology-Oncology and Stem Cell Research, 19, 126-137, 2025). Klingemann appears to teach a method that is the same as that claimed. Klingemann acquires an NK-92 population and provides for a subpopulation that is positive for CD56. See page 15, “Background” section. Klingemann enriches the modified NK-92 cells by providing them with a culture that includes IL-2 and IL-15. Within the method, Klingemann indicates that the culture medium is replaced every 3-4 days. See page 16, “Enriched CD56+ and PBMC cell culture” section. Klingemann is silent with respect to any production of exosomes or microvesicles.
As stated above, although Klingemann is silent with respect to the production of exosomes of microvesicles, Klingemann explicitly indicates that the medium contains IL-2 and IL-15, and is replaced every 3-4 days. Bearing this in mind, Abbassi unambiguously states that NK-92 cells naturally produce exosomes, and when they are exposed to IL-15, they will produce more effective exosomes. See page 126, “Abstract” section; page 128, “Exosome isolation, Quantification, and Confirmation” section; page 135, “Conclusion” section. While it is noted that Abbassi was published after the effective filing date of the instant invention, Abbassi is only used to show that the claimed feature would have inherently and necessarily been present in Klingemann. See MPEP 2112(II). As such, unless the Applicant can provide reasonable evidence that exosomes and microvesicles were not present in Klingemann, based upon the available prior art, they must have been inherently been present. Although Klingemann does not explicitly teach the exosome/microvesicle limitation, it appears as though Klingemann inherently anticipates the claimed method; however, since there is no explicit evidence for the production of these structures, the claims should also be rejected under 35 USC 103. See MPEP 2112(III).
With respect to claims 11, 12, 16, and 17, Klingemann provides for a method of producing a cell-based product by growing and isolating a subpopulation of NK-92 cells, wherein the cells are exposed to IL-2 and IL-15. The prior art notes that NK-92 cells inherently express exosomes/microvesicles, and that the exposure of the cells to IL-15 enhances this expression. Therefore, it stands to reason that if Klingemann exposed a subpopulation of NK-92 cells to IL-15, these cells must have inherently produced exosomes and microvesicles.
With respect to claims 13 and 21, Klingemann teaches X-Vivo10 serum-free medium. See page 15, “Methods” section. This medium is an aqueous solution.
With respect to claims 18, and 19, Klingemann supplements the serum-free medium with human serum. See page 16, “Enriched CD56+ and PBMC cell culture” section.
With respect to claims 22 and 23, Klingemann indicates that the subpopulation of NK-92 cells express the FcγRIII receptor, which is consistent with the claimed NK-92-CD16. See page 15, “Results” section; page 16, left column, 2nd [full] paragraph.
Claim 15 is 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 Klingemann, et al (Cytotherapy, 6, 15-22, 2004) evidenced by Abbassi, et al (International Journal of Hematology-Oncology and Stem Cell Research, 19, 126-137, 2025), and further evidenced by Tonn, et al (Cytotherapy, 15, 1563-1570, 2013). Klingemann and Abbassi are silent with respect to interferon-γ (IFN- γ) being present in the medium. First, it must be noted that the limitation states that the “medium further comprises [IFN- γ].” Given the broadest reasonable interpretation of the limitation, this compound merely needs to be present in the medium, it is not added by supplementation. Based upon this interpretation of the claim limitation, Tonn notes that NK-92 cells “produce significant levels of IFN- γ.” See page 1568, left column, last paragraph. If NK-92 cells produce IFN- γ, then IFN- γ must have inherently been present in the medium of Klingemann.
Claim Rejections - 35 USC § 103
Claims 14 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Klingemann, et al (Cytotherapy, 6, 15-22, 2004) and Arai, et al (Cytotherapy, 10, 625-632, 2008) and evidenced by Abbassi, et al (International Journal of Hematology-Oncology and Stem Cell Research, 19, 126-137, 2025). See the discussion of Klingemann and Abbassi above.
With respect to claim 14, Klingemann only teaches supplementation of the amino acid glutamine. See page 16, second-to-last paragraph. Klingemann does not teach further supplementation with serine and asparagine. Arai teaches methods of activating NK-92 cells prior to administering them for treatment; specifically, Arai activates the cells in a manner similar to that of Klingemann, wherein Arai exposes the cells to IL-2. See page 626, “Manufacturing of the NK-92 cell product” section. While not explicitly stated, the ordinary artisan is aware that amino acid supplementation is a routine addition to a culture method. There is nothing non-obvious about adding amino acids that are necessary to the growth of the cell-line. Furthermore, there is no evidence provided to suggest that the claimed supplementation unexpected changes the claimed cell product in a manner in which it is no longer consistent with the product disclosed in Klingemann.
With respect to claim 20, as stated above, Klingemann utilizes 10% human serum, instead of the claimed 5%. Abai, who activates the NK-92 cells in a manner that is consistent with Klingemann and that claimed, indicates that 2.5% human plasma was used in the culture method. See page 626, “Manufacturing of the NK-92 cell product” section. Based upon this variance, and the fact that 5% lies within the range provided in Klingemann and Abai, would suggest to the ordinary artisan that the amount of serum can be optimized in an obvious and predictable manner.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID W BERKE-SCHLESSEL whose telephone number is (571)270-3643. The examiner can normally be reached M-F 8AM-5:30PM.
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/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651
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