DETAILED ACTION
Notice of Pre-AIA or AIA 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.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is in response to the papers filed on 06/26/2026. Claims 1 and 16-23, 30, 37-41 are currently pending as per claims filed on 06/26/2026. Claims 2-15 are cancelled, claims 1 and 16 have been amended, and claims 37-41 have been newly added by Applicants’ amendment filed on 06/26/2026.
Applicant’s election without traverse of Group I, claims 1-17 in the reply filed on 12/02/2025 was previously acknowledged. The restriction requirement was previously made final.
Therefore, claims 1, 16, 17, and 37-41 are under examination to which the
following grounds of rejection are applicable. Claim 1 is an independent claim.
Priority
The instant application is a national stage entry under 35 USC 371 of PCT/US2021/028903 filed on 04/23/2021 which claims benefit of 63/015,013 filed on 04/24/2020.
Thus, the earliest possible priority for the instant application is 04/24/2020.
Withdrawn objections/rejection in response to Applicants’ arguments or
Amendment
Claim Objections
In view of Applicant’s amendment of claim 1 to spell out “SIRPα” and SIRPαlow” and claim 16 to spell out “SHP-1”, the claim objection has been withdrawn.
Claim Rejections - 35 USC § 112(d)
In view of Applicant’s amendment of cancelling claim 8, the 112(d) rejection has been withdrawn.
Claim Rejections - 35 USC §103
The rejection of claim(s) 1-17 (claims 2-15 now canceled) under 35 U.S.C. 103 as being unpatentable over Liu et al (WO 2017/180519 A1) ,Rios et al (Methods in Molecular Bio, page 311-320, 2017), Nilsson et al (Biochemical and Biophysical Research Communications, page 1304-1309, 2012), Christophi et al (Laboratory Investigation, page 742-759, 2009), Shorr et al (Drugs for the Geriatric Patient, page 631-632, 2007), Kundu et al (J. of Immunology, page 6529-6536, 2010), Motz et al (US Patent Publication Number. 2019/0298715 A1), as evidenced by Sigma Aldrich (Page 4, description, downloaded on 1/20/2026) has been withdrawn.
A response to Applicant’s arguments with regard to a withdrawn rejection is moot. A response to any argument pertaining to a new or maintained rejection can be found below.
Double Patenting – Non-statutory - Secondary References
The rejections of claims 1-17 (claims 2-15 now cancelled) on the ground of nonstatutory double patenting as being unpatentable over claim 1-11 of US Patent 11,026,972 B2 in view of Rios et al (Methods in Mol. Bio, page 311-320, 2017) has been withdrawn.
A response to Applicant’s arguments regarding a withdrawn rejection is moot.
New rejections in response to Applicants’ arguments or amendment
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.
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.
Claims 1, 16, 17, and 37-41 are newly rejected under 35 U.S.C. 103 as being unpatentable over Liu et al (WO 2017/180519 A1; as cited in office action filed 01/26/2026) and further in view of Eligini et al (J of Cellular Physiology, 2012, pages 1464-1472), Shorr et al (Drugs for the Geriatric Patient, page 631-632, 2007; as cited in office action filed 01/26/2026), Kundu et al (J. of Immunology, page 6529-6536, 2010; as cited in office action filed 01/26/2026), Utaisincharoen et al (Clin Exp Immunol, 2002; pages 467–473), Wang et al (EBioMedicine, 2018, pages 303–316), Zhou et al (Innate Immunity, 2012, 184-192) as evidenced by Sigma Aldrich (Page 4, description, downloaded on 1/20/2026; as cited in office action filed 01/26/2026). This is a new rejection necessitated by amendment of the claims in the response filed 06/26/2026.
The applied Liu reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(1). The publication dated for Liu is 19 October 2017. The earliest effective filing date of the instant application is April 23, 2020.
Therefore rejection under 35 U.S.C. 103 CANNOT be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02. Because the reference qualifies as prior art under 102(a)(1), the provisions of MPEP 717.02 do not apply.
Regarding claim 1, Liu teaches methods related to cancer treatment or, more generally to macrophage activation, by administering to the patient a first agent that suppresses the expression of SIRPα, inhibits the activity of SIRPα, or disrupts the interaction between SIRPα and CD47 and a second agent that activates macrophage phagocytosis (e.g., of cancer cells) (page 1-2, line 30-3). Liu teaches cancer treatment with macrophages can limit the signal that would otherwise suppress phagocytic activity, and by doing so (i.e. activating phagocytic activity), macrophages can then attack cancerous cells (page 1, lines 13-17). Liu teaches the first agent that suppresses the expression of SIRPa can be a nucleic acid that suppresses the expression of SIRPa and can be a ligand for a Toll-like receptor (TLR), for example, polyinosinic:polycytidylic acid (poly I:C), a CpG oligonucleotide, or a cytokine such as IFNγ and the SIRPα inhibitors can be in any one or more combination (page 2-3, lines 15-5).
However, Liu does not teach (a) isolating monocytes from a biological sample; (b) differentiating the monocytes in vitro to produce macrophages. Liu does not teach that the composition additionally comprises human recombinant interferon-alpha-2a in step (c).
However, one of ordinary skill in the art would have considered the teachings of
Eligini and Shorr as these references are analogous prior art pertaining to isolation of monocytes and diff
Eligini teaches that macrophages derived in vivo are heterogenous in phenotype due to environmental influences and are not easy to obtain (page 1464, left col, para 1) and that monocyte-derived macrophages (which are isolated from venous blood (materials and methods)) are commonly accepted as a good substitute of macrophages as distinct phenotypes can be obtained by exposure to different agents, allowing for controlled differentiation (page 1464, right col, para ), reading on claim 1 step (b).
Moreover, Shorr teaches interferon alfa-2a (Brand name: Roferon-A (alfa-2a)) is a biologic response modifier that increases phagocytic action of macrophages (page 631-632).
It would have been prima facie obvious to use the teachings of Eligini for using macrophages which have been differentiated from monocytes that were isolated from a biological sample with Liu’s method of producing macrophages with marked reduction in SIRPα expression since Eligini teaches that monocyte-derived macrophages (wherein the monocytes are derived from blood) are a good substitute for in vivo heterogenous macrophages. Furthermore, it would have been obvious to include IFNα in the composition recited in step (c) since Shorr teaches that IFNα increases phagocytic action of macrophages and Liu teaches that increased phagocytotic activity by contacting macrophages with a nucleic acid that suppresses the expression of SIRPa comprising a ligand for a Toll-like receptor (TLR), for example, polyinosinic:polycytidylic acid (poly I:C), a CpG oligonucleotide, or a cytokine such as IFNγ and the SIRPα allows macrophages to attack cancerous cells. One would be motivated to do so to have a more robust and efficient method of treating cancer by including factors known to enhance cancer-killing characteristics of macrophages and derive the macrophages from a more defined source and would have a reasonable expectation of success
“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). In the instant case, both Liu and Shorr teach compositions to activate macrophages to have phagocytic action,
With regard to claim 1, line 9, “thereby generating a population of macrophages with marked reduction of SIRPα cell-surface expression (SIRPαlow) relative to untreated macrophages”, it is noted that the claim is directed to an inherent result based on the methodology of the contacting macrophages with the claimed composition resulting in marked reduction of SIRPα cell-surface expression SIRPαlow. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). It is noted that, if the prior art discloses identical chemical structure, the properties applicant discloses and/or claims are necessarily present, In re Spada, 911 F.2d 705, 709, 15 USPQ2d. As such the functional limitations would be present in the identical compounds of the composition taught by the combined references of Liu andShorr and would therefore elicit these effects whenever it is contacted with said composition .Regarding claim 16, the teachings of Liu, Eligini and Shorr render obvious claim 1. Moreover, Liu teaches SIRPα can also be inhibited by inhibiting the SIRPα signaling pathway and studies have shown that several tyrosine kinase inhibitors inhibit SIRPα cytoplasmic domain phosphorylation and recruitment of SHP-1/2. Accordingly, these agents are useful in the methods where macrophages are conditioned to downregulate the activity of SIRPα (page 18, lines 3-6), rendering obvious further comprising contacting the macrophages with a SHP-1 inhibitor.
Regarding claim 17 and 37, the teachings of Liu, Eligini and Shorr render obvious claim 1 and 16.
However, the combined teachings of Liu, Eligini and Shorr do not teach wherein the SHP-1 inhibitor is an irreversible SHP-1 inhibitor (claim 17) and wherein the SHP-1 inhibitor is selected from a species recited in a group recited in claim 37.
Kundu teaches “TPI-1 and its analogs were identified as more effective than SSG in SHP-1 inhibition, immune cell activation, and anti-tumor action. Our results provide important evidence supporting targeting SHP-1 to activate immune cells as an anti-cancer strategy and designate TPI-1 and the analogs as promising leads” (page 6530, para 1) where TPI-1 is an irreversible SHP-1 inhibitor as evidenced by Sigma Aldrich (page 4, Description; Downloaded on 1/20/2026).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to select TP1-1 as an irreversible SHP-1 inhibitor from Kundu since Kundu teaches that TPI-1 is an effective SHP-1 inhibitor and leads to immune cell activation and anti-tumor action, thus one would be motivated to combine the teachings to generate an improved method for using macrophages as a cancer treatment.
Regarding claim 38, the teachings of Liu, Eligini and Shorr render obvious claim 1. Moreover, while Liu teaches treating macrophages by exposing to 100 units/ml of IFN-γ which corresponds to, Liu does not teach a concentration of 40-200 ng/ml.
Wang teaches stimulating in vitro cultured macrophages with 100 ng/ml of IFN-γ to activate macrophages which leads to sustained cell viability and pro-inflammatory activation (abstract, page 303; 4.1. Macrophage Differentiation, page 305).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of Liu, Eligini and Shorr to contact macrophages with a composition comprising between 40-200 μg/ml of IFN-γ since Wang teaches that this concentration can elicit macrophage activation. One would be motivated to do so to optimally activate macrophages as a treatment method and have a reasonable expectation of success.
Applicant is reminded that differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.") See MPEP 2144.05 II. A.
Regarding claim 39, the teachings of Liu, Eligini and Shorr render obvious claim 1.
The combined teachings do not teach IFNα is present at a concentration of 40-200 ng/ml.
Greenwell-Wild teaches that culture of human macrophages derived from isolated monocytes with 10 ng/mL of IFNα led to increased expression of anti-viral genes, demonstrating a role of IFNα for macrophage antiviral activity. While the concentration recited by Greenwell-Wild does not fall within the claimed range, Applicant is reminded that differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See MPEP 2144.05 II. A.
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of Liu, Eligini and Shorr to contact macrophages with a composition comprising between 10 μg/mL of IFNα since Greenwell-Wild teaches that this concentration can elicit antiviral gene expression in macrophages derived from isolated monocytes. One would be motivated to do so to generate macrophages with antiviral activity as a treatment method and have a reasonable expectation of success.
Regarding claim 40, the teachings of Liu, Eligini and Shorr render obvious claim 1.
However, the combined teachings do not teach wherein the CpG oligodeoxynucleotide is present at a concentration of 1-5 μg/ml.
Utaisincharoen teaches that 0.05-10 μg/ml of synthetic oligonucleotide containing unmethylated cytosine (CpG ODN) can activate mouse macrophages indicated by elevated nitric oxide production (page 468, right col, Results; Figure 1).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of Liu, Eligini and Shorr to contact macrophages with a composition comprising between 1-5 μg/ml of CpG oligodeoxynucleotides since Utaisincharoen teaches that this concentration can elicit macrophage activation. One would be motivated to do so to optimally activate macrophages as a treatment method and have a reasonable expectation of success.
Regarding claim 41, the teachings of Liu, Eligini and Shorr render obvious claim 1.
The combined teachings do not teach wherein the Poly I:C is present at a concentration of 1-5 μg/ml.
Zhou teaches that Poly I:C can activate toll-like receptor 3 (TLR3) which is important for inflammatory and immune defense responses (abstract, page 1) and showed that the antiviral activity of macrophages, through expression of IFNs, was elevated when macrophages were cultured with 1 μg/mL or 10 μg/mL (Figure 4).
It would have been prima facie obvious to one of ordinary skill, in the art at the time of the effective filing date, to modify the teachings of Liu, Eligini and Shorr to contact macrophages with a composition comprising between 40-200 μg/ml of IFN-γ since Zhou teaches that this concentration causes macrophages to express IFNs known to be important in activation and antiviral activity. One would be motivated to do so to enhance the activity of macrophages as a treatment method and have a reasonable expectation of success.
Response to Applicant’s arguments as they apply to rejection of claims 1, 16, 17, and 37-41 under 35 USC § 103
Applicant’s arguments filed 06/26/2026 have been fully considered but not
persuasive.
Applicant asserts that 1) the claimed method unexpectedly imparts properties to macrophages subjected to the same that contribute to tumor cell eradication while reducing problematic side effects, more specifically the invention describes methods to downregulate SIRPα expression in macrophages while simultaneously activating phagocytosis (Page 9 of Remarks); 2) the cited references, even when combined, fail to provide the reasoning establishing a motivation to combine; and 3) the cited references, even when combined, fail to provide a reasonable expectation of success.
Regarding argument 1, “for unexpected results to be evaluated, the results presented must be compared to the expected-the closest prior art - results. See MPEP 716.02(e). ("an affidavit or declaration under 37 CFR 1.132 must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness" - emphasis added). Overall, the results of the macrophages having reduced expression of SIRPα demonstrating tumor-eradicating behavior indeed were found in the art of Liu. Liu teaches using methods that reduce SIRPα expression or inhibits the activity of SIRPα in macrophages without necessarily knocking out SIRPα or blocking SIRPα-CD47 interaction, such as using ligands, cytokines, and nucleic acids (Summary, para 2-3), and for the same function of attacking cancer cells and activating phagocytosis in macrophages. Therefore, it would be expected that agents in the composition recited in the instant claims would indeed provide the expected result of attacking cancer cells and activating phagocytosis in macrophages. Nevertheless, to determine what is "expected" in the present case, one would need to know, at the very least, what results exposing macrophages to agents that reduce SIPRα expression and increase phagocytosis in the manner taught by Liu (the closest prior art) yielded.
On a similar token, the art of Liu indeed teaches methods of suppressing the expression of SIRPα in macrophages using a first agent and activating macrophage phagocytosis using a second agent. More specifically, Liu teaches that the reduction in SIRPα expression can be achieved by exposing macrophages to the first agent which can be poly I:C, a CpG oligonucleotide, or a cytokine such as IFNγ and that these can be used in combination (page 2-3 of Liu) to achieve suppression of SIRPα. Regarding the combined effect of macrophage phagocytosis in the claimed invention, Liu teaches that upon CD47 extracellular binding, SIRPα alters tyrosine phosphorylation in the intracellular ITIMs, which subsequently recruit SH2-containing tyrosine phosphatase (SHP1/2) and initiate inhibitory signaling events that suppress macrophage phagocytosis (page 13, line 19-23). Hence, Liu provides motivation that SHP1/2 could be a target for alleviating inhibitory signaling for macrophage phagocytosis, thus SHP1/2 inhibition would augment macrophage phagocytosis. Since Liu teaches using a second agent for enhancing macrophage phagocytosis, it is obvious that a SHP-1 inhibitor could be used as the second agent. While the addition of IFNα is not taught by Liu, IFNα was known to increase phagocytosis in macrophages as taught by Shorr, thus its effects could be predicted even when combined with the agents IFNγ, CpG oligodeoxynucleotide, and Poly I:C. Hence collectively, the teachings of Liu and Shorr teach the downregulation of SIRPα in macrophages by using agents IFNγ, CpG oligodeoxynucleotide, and Poly I:C, and the inclusion of SHP-1 inhibitor to increase phagocytosis, thus rendering the claim 1 and 16 obvious. The instant claims require contacting the macrophages with a composition that comprises recombinant human
interferon-gamma (IFNy), recombinant human interferon-alpha A2 (IFNa), CpG
oligodeoxynucleotide, and polyinosinic:polycytidylic acid (Poly I:C), but the instant claims are not so limited such that this is the only possible combination contacting macrophages. The claims are "open" and thus lend themselves to additional transgenes, or additional down regulators of SIRPa cell-surface expression
relative to untreated macrophages. There is no requirement that the only composition of instant claim 1 is so limited as argued by Applicant. Thus, the combined disclosure of Liu and Shorr is relevant, since the disclose agents able to activate macrophages, precisely because Liu and Shorr recognize reduction of SIRPα cell-surface expression aids in the treatment of cancer and activation of macrophage phagocytosis.
Regarding argument 2, Applicant is directed to the rebuttal above for argument 1. In essence, Liu indeed teaches enhancing the phagocytic activity of a macrophage by suppressing the expression of SIRPα using agents such as IFNγ, CpG oligodeoxynucleotide, and Poly I:C.and Liu teaches that SHP-1 is involved in SIRPα signaling, thus indicating an additional target for inhibition. Since Shorr teaches IFNα can also increase phagocytosis in macrophages, it would have been obvious to combine Shorr and Liu to arrive at a composition including several factors known to increase macrophage phagocytosis activity. The examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
Regarding argument 3, while Liu does not teach IFNα in the SIRPα-reducing composition, Liu does teach the combination of agents IFNγ, CpG oligodeoxynucleotide, and Poly I:C for enhancing macrophage phagocytosis, and when combined with Shorr, one would indeed have a reasonable expectation of success since Shorr that IFNα can increase macrophage phagocytosis. As Liu teaches the composition can have a combination of agents, one of ordinary skill in the art would expect that the addition of IFNα could be successful in increasing macrophage phagocytosis when combined with the aforementioned agents.
Double Patenting - Non-statutory – Secondary Reference(s)
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 16, 17, and 37-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-11 of US Patent 11,026,972 B2 in view of Eligini et al (J of Cellular Physiology, 2012, pages 1464-1472) and Shorr et al (Drugs for the Geriatric Patient, page 631-632, 2007; as cited in office action filed 01/26/2026). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over the cited claims of US Patent 11,026,972 (reference patent ‘972). This is a new rejection necessitated by amendment of the claims in the response filed 06/26/2026.
Claim 1 of reference patent ‘972:
“A method of generating macrophages with enhanced cancer phagocytosis, the method comprising:
(a) providing a biological sample from a subject, wherein the biological sample comprises macrophages;
(b) exposing the sample to an effective amount of a first composition comprising at least 100 units/ml IFNγ to suppress the expression or activity of signal regulatory protein α (SIRPα); and
(c) exposing the sample from step (b) to an effective amount of a second composition that activates Protein kinase C (PKC)-Spleen tyrosine kinase (Syk) pathway, thereby generating macrophages with enhanced cancer phagocytosis.”
Claim 5 and 6 of patent ‘972 recites “the method of claim 1, wherein the first composition further comprises a Toll-like receptor (TLR) ligand” and “the method of claim 5, wherein the TLR ligand comprises a CpG oligonucleotide or a polyinosinic:polycytidylic acid (poly I:C).”, respectively.
Claim 1 of the instant application recites:
A method for producing macrophages with marked reduction in signal regulatory protein alpha (SIRPa) expression, comprising:
(a) isolating monocytes from a biological sample;
(b) differentiating the monocytes in vitro to produce macrophages; and
(c) contacting the macrophages with a composition that comprises recombinant human interferon-gamma (IFNy), recombinant human interferon-alpha A2 (IFNa), CpG oligodeoxynucleotide, and polyinosinic:polycytidylic acid (Poly I:C),
thereby generating a population of macrophages with marked reduction of SIRPa cell-surface expression (SIRPαlow), relative to untreated macrophages.
It is noted that claim 1 (step (c)) of reference patent ‘972 is a species of the genus claimed in instant claim 1.
The instant claims differ from claims 1-11 by requiring isolating monocytes from a biological sample and differentiating the monocytes in vitro to produce macrophages.
However, before the effective filing date of the claimed invention, Eligini teaches that macrophages derived in vivo are heterogenous in phenotype due to environmental influences and are not easy to obtain (page 1464, left col, para 1) and that monocyte-derived macrophages (which are isolated from venous blood (materials and methods)) are commonly accepted as a good substitute of macrophages as distinct phenotypes can be obtained by exposure to different agents, allowing for controlled differentiation (page 1464, right col, para ), reading on claim 1 step (b).
Moreover, Shorr teaches interferon alfa-2a (Brand name: Roferon-A (alfa-2a)) is a biologic response modifier that increases phagocytic action of macrophages (page 631-632).
Therefore, in view of the benefit of differentiating macrophages from monocytes derived from in vivo biological samples and IFNα being capable of increasing phagocytic action macrophages, it would have been obvious for one of ordinary skill in the art to include the isolation and differentiation step as taught by Eligini.and the IFNα as taught by Shorr, in the claimed method in an attempt to maximize the initial cell population and create uniform macrophages phenotypes and maximize the phagocytic activity of macrophages. Thus, the claims of the instant application are encompassed by, or overlap in scope significantly with, the claims of U.S. Patent 11,026,972.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 Juliana Candelaria whose telephone number is (571)272-5488. The examiner can normally be reached Monday - Friday 8am - 5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JULIANA IRENE CANDELARIA/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
Prosecution Insights