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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/04/2025 has been entered.
Status of the Claims
Claims 1-13, 15-19 are pending.
Claims 2-9 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (as acknowledged by Applicant), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/20/2024.
Claims 1, 10-13, 15-19 are examined herein as they read on the elected subject matter.
Claim Objections
Claims 10, 12, 15, 17 and 18 are objected to because of the following informalities: the claims recite “IFNy” which appears to be a simple typographical error that should read “IFNγ” which would be consistent with the specification and with standard practiced recognized in the field. Appropriate correction or clarification is required.
Claims 10, 12, and 13, are also objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims and upon correction of the other objection to the claims. These claims require a combination of agents that includes a TLR ligand, IFN-gamma and IL-6.
Claim Rejections - 35 USC § 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 11, are rejected under 35 U.S.C. 103 as being unpatentable over Cioffi et al (Clinical Cancer Research, February 2015; of record – IDS citation), in view of Smith et al (Neurochemical Research, 1998; of record – IDS citation).
Cioffi et al teaches macrophages obtained from a subject were treated with IFNγ (an agent that suppresses expression or activity of SIRPa, and LPS to generate M1-polarized macrophages, and IFNγ/LPS activated macrophage phagocytosis of cancer cells (page 2326, column 2, paragraph 2; page 2329, column 1, paragraph 1).
Coiffi et al does not teach that the macrophages treated with IFN and LPS were human macrophages or treating macrophages with an agent that activates PKC-Syk pathway, such as PMA.
Smith et al teaches treatment of macrophages with PMA stimulates macrophage phagocytosis (see abstract; page 429, column 1, second paragraph; page 430, Figures 1-2).
Although neither Coffi et al. nor Smith et al. utilized macrophages from human subjects, it is noted that Coffi and Smith utilized macrophages from rodents, which are art-recognized models for human subjects.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to combine Coiffi et al and Smith et al to make a composition comprising IFNγ, PMA and a macrophage obtained from a human subject, with a reasonable expectation of success.
The combination of prior art cited satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 USPQ2d 1385 (2007):
“Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.”
In this case, rationale (A) Combining prior art elements according to known methods to yield predictable results, and/or (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success apply.
It is also noted that MPEP 2144.06 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) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious).
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Cioffi et al (Clinical Cancer Research, February 2015; of record – IDS citation), in view of Whitmore et al. (Cancer Research (2004), vol. 64, pages 5850-5860).
The teachings of Coiffi et al., as applied here, are described in the rejection above.
Coiffi et al. does not teach using the TLR ligands poly I:C and CpG oligonucleotide to activate macrophages derived from a human subject.
Whitmore et al. teaches using poly I:C and CpG oligonucleotides to stimulate antitumor activity of macrophage (e.g., abstract, Figure 1, page 5859 first column first full paragraph).
Although neither Coffi et al. nor Whitmore et al. utilized macrophages from human subjects, it is noted that Coffi and Whitmore utilized macrophages from rodents, which are art-recognized models for human subjects.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to combine Coiffi et al and Whitmore et al to make a composition comprising IFNγ, CpG oligonucleotide, poly I:C and a macrophage obtained from a human subject, with a reasonable expectation of success.
In this case, rationale (A) Combining prior art elements according to known methods to yield predictable results, and/or (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success apply. Furthermore, MPEP 2144.06, as cited above, indicates that its prima facie obvious to combine 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.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Cioffi et al (Clinical Cancer Research, February 2015; of record – IDS citation), in view of Whitmore et al. (Cancer Research (2004), vol. 64, pages 5850-5860) and Hori et al. (Cancer Research (1987) vol 47, pages 5868-5874).
The teachings of Coiffi et al., and Whitmore, as applied here, are described in the rejection above.
Neither Coiffi et al. nor Whitmore et al. teach using TNF-alpha to activate macrophages from a human subject.
Hori et a. Tumor Necrosis Factor (TNF, also known as TNF-alpha) used in combination with IFN-gamma resulted in synergistic induction of tumoricidal activity in macrophages (see abstract, Figure 3, etc.).
Although Coffi et al., Whitmore et al. and Hori et al. did not utilize macrophages from human subjects, it is noted that Coffi, Whitmore and Smith utilized macrophages from animals which are an art-recognized models for human subjects.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to combine Coiffi et al., Whitmore et al., and Hori et al. to make a composition comprising IFNγ, CpG oligonucleotide, poly I:C, TNF-alpha, and a macrophage obtained from a human subject, with a reasonable expectation of success.
In this case, rationale (A) Combining prior art elements according to known methods to yield predictable results, and/or (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success apply. Furthermore, MPEP 2144.06, as cited above, indicates that its prima facie obvious to combine 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.
Allowable Subject Matter
Claim 19 is allowed. It is noted that claims 10, 12, 17 and 18 are only objected to, but would be allowable if the objections were overcome.
Response to Arguments
Applicant's arguments filed 07/09/2025 have been fully considered but they are not persuasive.
Applicant argues that the claims have been amended to require that the monocyte or macrophage derived from a monocyte is obtained from a human subject.
This is not persuasive because the animals from which the monocytes/macrophages were derived are art-recognized animal models for humans. Thus, although the references do not teach that the cells were derived from human subjects, since the animals from which the cells were derived are art-recognized models for humans, it would have been prima facie obvious to one of ordinary skill in the art to use macrophages obtained from a human subject with a reasonable expectation of success. The motivation and expectation of success is based on the fact that the animal models are art-recognized models for human.
Therefore, Applicant’s arguments are not persuasive.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to J. E. Angell whose telephone number is (571)272-0756. The examiner can normally be reached Monday-Friday (8:30-5:00).
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J. E. Angell
Primary Examiner
Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637