DETAILED ACTION
This Action is in response to the communication filed on 06/10/2026.
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 .
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Claims 2-9 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (as acknowledged by Applicant), there being no allowable generic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.
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Claims 2-9 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (as acknowledged by Applicant), there being no allowable generic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 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 also teaches generating M1 and M2 monocyte-derived human macrophages derived but does not teach that the human macrophages were treated with IFN and LPS, nor does Coffi teach 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 which were treated with the required agents, 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.
Claims 10, 12, 17 and 18 are 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.
Response to Arguments
Regarding the objection to claims 10, 12, 15, 17, and 18 for the recitation “IFNy”, the amendment obviates the objection; thus the objection is withdrawn.
With respect to the rejections under 35 USC 103, Applicant's arguments filed 06/10/2026 have been fully considered but they are not persuasive. Applicant argues that the cited references, even when combined, fail to teach all the elements of the instant claims, fail to provide the articulated reason establishing a motivation to combine, and fail to provide a reasonable expectation of success of arriving at the claimed invention. Applicant acknowledges that Coiffi teaches differentiation of human monocytes into macrophages and subsequent polarization into M1 oe M2 macrophages , but teaches wholly different agents for said differentiation and subsequent polarization and does not teach a composition comprising human monocytes or macrophages in combination with the agents recited in the claims.
In response, although Cioffi does not teach a composition comprising human monocytes or macrophages in combination with one or more agents that suppress the expression or activity of SIRPα,and one or more agents that activate PKC-Syk pathway, Cioffi does teach treating rodent macrophages with IFNγ and LPS to generate M1-polarized macrophages, and IFNγ/LPS activated macrophage phagocytosis of cancer cells, while Smith teaches treatment of PMA stimulates macrophage phagocytosis, as indicated above. As indicated above, Cioffi does teach human M1-polarized macrophages as well as rodent activated macrophages, both of which can be used for macrophage phagocytosis of cancer cells even though they are produced differently. Since Smith teaches PMA treatment stimulates macrophage phagocytosis, it would have been obvious to combine IFNγ/LPS and PMA treatment of macrophages to stimulate macrophage phagocytosis. Furthermore, since it was known that human macrophages could be stimulated to become phagocytic, albeit by using different agents, it would have been obvious to try using the combination of IFNγ/LPS and PMA treatment on human macrophages as these agents were known to stimulate rodent macrophage phagocytosis.
With respect to the limitations required by claim 15, Whitmore teaches using poly I:C and CpG oligonucleotides to stimulate antitumor activity of macrophage. As such, it would have been prima facie obvious combine Coiffi and Whitmore to make a composition comprising IFNγ, CpG oligonucleotide, poly I:C and a macrophage obtained from a human subject to stimulate macrophage anticancer activity.
With respect to claim 16, Hori teaches Tumor Necrosis Factor (TNF, also known as TNF-alpha) used in combination with IFN-gamma resulted in synergistic induction of tumoricidal activity in macrophages as indicated above. Thus, it would have been prima facie obvious to combine Coiffi, Whitmore, and Hori to make a composition comprising IFNγ, CpG oligonucleotide, poly I:C, TNF-alpha, and a macrophage obtained from a human subject to stimulate macrophage anticancer activity.
Furthermore, the positive results demonstrating that required agents (IFNγ, PMA, CpG oligonucleotide, poly I:C, TNF-alpha) stimulate rodent macrophage anticancer activity provides a reasonable expectation that the combination would be successful at stimulating human macrophages in the same was as well.
With respect to the argument that the cited prior art does not provide motivation to generate the claimed combination, the Examiner’s position is that the positive results demonstrating stimulation of macrophage anticancer activity in rodent macrophages provides both a motivation to try the combination with human macrophages to stimulate anticancer activity, and the positive results also provide the basis for a reasonable expectation of success. The fact that the prior art taught a different method for stimulating macrophage anticancer activity does not teach away from (i.e., does not negate all motivation for) trying a different method, such as a different combination of agents that successfully stimulate anticancer activity of non-human macrophages.
Thus, the cited prior art, in combination, does teach all of the limitations required by the claims, provides a reason to combine (to stimulate human macrophage anticancer activity), and provides the basis for a reasonable expectation of success.
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).
Therefore, Applicant’s arguments are not persuasive.
Conclusion
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.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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J. E. Angell
Primary Examiner
Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637
Prosecution Insights