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 .
1. Claims 1-46 have been cancelled. Claims 48-57 have been amended.
Claims 47-60 are pending and under examination.
2. The objections to claims 48-57 are withdrawn in response to the amendments filed on 01/23/2026.
Claim Rejections - 35 USC § 103
3. 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 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.
4. Claims 47, 48, 58, and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Jang et al. (Biomaterials, 2012, 33: 5584-5592), in view of Alam et al. (Natural Killer Cells, 2017, p. 139-160).
Jang et al. teach NK cells comprising PEI-coated magnetic nanoparticles, where PEI increase the stability of the magnetic nanoparticles; the magnetic nanoparticles are useful for tumor therapy. Jang et al. also teach injecting mice with a composition comprising the loaded NK cells and culture medium (claims 47 and 58) (see Abstract; paragraph bridging p. 5584 and 5585; p. 5585, column 2, second paragraph; p. 5587, column 2, last paragraph). While Jang et al. do not specifically teach saline (claim 60), one of skill in the art would have found obvious to suspend the loaded NK cells in any isotonic solution, including isotonic saline, to achieve the predictable result of obtaining a composition suitable for injection.
Jang et al. do not teach targeting the nanoparticles to the NK granules (claims 47 and 58). However, doing so is suggested by the prior art. For example, Alam teaches that, upon recognition, the NK cells specifically kill the target tumor cells via directing their granule content to the target tumor cells, while sparing the bystander cells; Alam et al. teach that the granules express the membrane protein CD107a (also known as LAMP-1) (see p. 140; see p. 154, last paragraph). Based on these teachings one of skill in the art would have reasonably concluded that directing the nanoparticles to the NK granules would result in their incorporation into the granules and their specific release to the target tumor cells upon NK cells activation. One of skill in the art would have found obvious to modify Jang et al. by loading the NK cells with nanoparticles conjugated with an anti-LAMP-1 antibody to achieve the predictable result of obtaining a therapeutic composition suitable to specifically target the tumor cells.
With respect to claim 48, one of skill in the art would have found obvious to apply the teachings of Jang et al. and Alam et al. to NK cells isolated from a cancer patient to achieve the predictable result of obtaining a composition suitable to treat the cancer in the patient.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
5. Claims 47-52, 58, and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Jang et al. taken with Alam et al., in further view of both Machanda et al. (Colloids and Surfaces B: Biointerfaces, 2010, 75: 260-267) and Ferrautto et al. (Nanoscale, 2017, 9: 99-103).
The teachings of Jang et al. and Alam et al. are applied as above for claims 47, 48, 58, and 60. Jang et al. and Alam et al. do not teach nanoparticles coated with ICG and encapsulating DOX (claims 49, 50, and 52). However, Jang et al. teach that the nanoparticles could be used for drug delivery and magnetic hyperthermia therapy (see p. 5591, column 1). Machanda et al. teach PLGA encapsulating ICG and DOX; delivering both ICG and DOX facilitates the combined hyperthermia-chemotherapy effect. Machanda et al. teach that PLGA is widely used because it is biocompatible and biodegradable and can also be functionalized with antibodies for targeted delivery (see Abstract; paragraph bridging p. 260 and 261; p. 267, column 1). Based on these teachings, one of skill in the art would have found obvious to modify Jang et al. and Alam et al. by further encapsulating ICG and DOX in the nanoparticles and also replacing PEI with PLGA to achieve the predictable result of obtaining a composition suitable for efficient cancer therapy (claim 51). MPEP 2144.06 [R-6] I states:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
The prior art also teaches that ICG could be either encapsulated or coated on the surface of nanoparticles (claim 49) (see Ferrautto et al., p. 99, column 2). One of skill in the art would have found obvious to coat the nanoparticles with ICG instead of encapsulating it, to achieve the result of obtaining a composition suitable for enhanced cancer therapy.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
6. Claims 47, 48, 53, 54, 58, and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Jang et al. taken with Alam et al., in further view of Calvet et al. (Cancer Res., 2016, 76, Poster 1197).
The teachings of Jang et al. and Alam et al. are applied as above for claims 47, 48, 58, and 60. Jang et al. and Alam et al. do not specifically teach a humanized anti-LAMP-1 monoclonal IgG antibody (claims 53 and 54). However, such antibodies were used in the prior art, for example by Calvet et al. (see Abstract). Using a humanized anti-LAMP-1 monoclonal antibody as the anti-LAMP-1 antibody would have been obvious to one of skill in the art to achieve the predictable result of loading the nanoparticles into the granules of the NK cells. While the prior art does not specifically teach that the antibody is an IgG antibody, there is no evidence of record that specifically using an IgG antibody is superior to the antibody taught by the prior art. As per MPEP § 716.02, [a]ny differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
7. Claims 47, 48, and 55-60 are rejected under 35 U.S.C. 103 as being unpatentable over Jang et al. taken with Alam et al., in further view of Schnarr et al. (Adv. Healthcare Mater., 2013, p. 1-7).
The teachings of Jang et al. and Alam et al. are applied as above for claims 47, 48, 58, and 60. Jang et al. and Alam et al. do not teach gold nanoparticles (claims 55-57 and 59). Schnarr et al. teach that loading cells with gold nanoparticles for photothermal ablation of cancer (see p. 1-2; p. 4, column 2, first full paragraph). One of skill in the art would have found obvious to further load the NK cells with gold nanoparticles to achieve the predictable result of obtaining a composition suitable for efficient cancer therapy. MPEP 2144.06 I states:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
The specification discloses that gold nanoparticles normally exhibit a plasmon resonance of 800 ± 10 nm (see p. 16, lines 16-19) (claim 57).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Response to Arguments
8. The arguments are not found persuasive because they address the references individually. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In this case, based on the combination of Jang and Alam, one of skill in the art would have reasonably concluded that directing the nanoparticles to the NK granules would result in selective delivery of drugs and hyperthermia therapy to the cancer cells, while sparing the bystander cells. One of skill in the art would have reasonably expected that the NK cells would also be spared because Alam teaches that, upon degranulation CD107a is transiently transferred on the surface of NK cell to protect them from being damaged by their own perforin and granzyme release (see p. 140, last paragraph)
For these reasons, the following arguments are not found persuasive: (1) selective release is neither recognized nor suggested by the prior art; and (2) nothing in Jang suggests that NK cells would maintain viability, degranulation capacity, and cytotoxic activity.
The applicant did not provide any evidence indicating that.
The following arguments are not found persuasive because they are not supported by any evidence; (1) targeting the nanoparticles to the granules would require highly directed engineering; (2) lack of reasonable expectation of success; (3) loading the granules with nanoparticles would impair degranulation/cytotoxic activity; (4) the argument that using PLGA in lytic granules would require specific, non-trivial technical design to ensure stability, photoactivation, and preservation of NK cell physiology; and (5) PLGA degradation withing granules must be avoided.
It is also noted that:
Jang teaches that loading the NK cells with nanoparticles does not affect their cytotoxic activity. Thus, one of skill in the art would have reasonably expected that the same would be true when the nanoparticles are directed to the granules. The applicant did not provide any evidence to the contrary.
Systemically administered PLGA nanoparticles are also subjected to degradation within the acidic endosomal environment upon internalization by cells and are used for controlled drug release.
With respect to arguments addressing Schnarr, this reference does not have to teach or suggest directing the nanoparticles to the NK cell granules.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Conclusion
9. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ILEANA POPA/Primary Examiner, Art Unit 1633