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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 02/26/2026 has been entered.
Claims 1-3, 5-11, 13, 15, 17, 30, 40, 46-49, 51 and 75 are currently pending.
Claims 1-3, 5-11, 7, 13, 15 and 17 have been amended by Applicant.
Claims 30, 40, 46-49, 51 and 75 have been withdrawn.
Claims 1-3, 5-11, 13, 15 and 17 are currently under examination on the merits in the instant Office Action.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This Office Action contains New Rejections Necessitated by Amendments.
Claim Objections - Withdrawn
The claim objection has been withdrawn.
Claim Rejections – Withdrawn
The rejection of claims 1-3, 5-11, 13, 15, and 17 under 35 U.S.C. 103 as being unpatentable over Hacohen (WO 2015095811 A2 Date Published 2015-06-25) in view of Koki (Cancer Control 2002 Mar-Apr;9(2 Suppl):28-35), Langley (Br J Cancer. 2011 Aug 16;105(8):1107–1113), Johnson (Opinion on Biological Therapy, 7(4), 449–460), Wilhelm (Int J Cancer. 2011 Jul 1;129(1):245-55. Epub 2011 Apr 22), and Park (J Immunol. 2013 Apr 15;190(8):4103-15. Epub 2013 Mar 15) has been withdrawn.
The rejection of claims 1, 4 and 12 under 35 U.S.C. 103 as being unpatentable over Hacohen (WO 2015095811 A2 Date Published 2015-06-25) in view of Koki (Cancer Control 2002 Mar-Apr;9(2 Suppl):28-35), Langley (Br J Cancer. 2011 Aug 16;105(8):1107–1113) and Jain (US 20130287688A1 Date Published 2013-10-31) has been withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 112(b) – Maintained
Claims 1-3, 5-11, 13, 15 and 17 remain rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AlA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AlA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 contains the trademark/trade name MONTANIDE. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a proprietary oil-in-water emulsion adjuvant composition, accordingly, the identification/description is indefinite. Because all pending claims are dependent on claim 1, claims 2, 3, 5-11, 13, 15 and 17 are also rejected here.
Response to Arguments
In the Reply of 2/26/26, Applicant amended the claims, argues pending claims are definite, and requests withdrawal of this this rejection.
The amendments to the claims and the arguments found in the Reply of 2/26/26 have been carefully considered, but are not deemed persuasive. The claims remain indefinite and the rejection is maintained for the reasons stated above.
Claim Objections – Necessitated by Amendments
Claims 1 and 10 are objected to because of the following informalities:
Claim 1 recites the term “mannide-mono-oleate” which is not the typical manner this chemical or emulsifier is normally presented. Instead, it is typically written as “mannide monooleate”.
Claim 10 appears to have a typographical error. The term “(e)” recited in the claim should be “(f)”.
Appropriate correction is required.
New Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 112(b) – Necessitated by Amendments
Claim 1 recites “(e.g., MONTANIDETM or DepotVAXTM)”. Firstly, two adjuvants are recited in parenthesis. Therefore, it is unclear how or if adjuvants in parenthesis limit the claims.
Secondly, claim 1 recites the term “e.g.” which is taken to mean “for example”. The metes-and-bounds of the claims are unclear because it is unclear how, or if, possible limitations following “e.g.” limits the claims.
Thirdly, claim 1 contains the trademark/trade name DepoVaxTM. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a proprietary oil-based adjuvant composition, accordingly, the identification/description is indefinite.
Because all pending claims are dependent on claim 1, claims 2, 3, 5-11, 13, 15 and 17 are also rejected here.
Claim Rejections - 35 USC § 103 – Necessitated by Amendments
Claims 1-3, 5-11, 13, 15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Hacohen et al. (WO 2015095811 A2 Date Published 2015-06-25) in view of Koki et al. (Cancer Control 2002 Mar-Apr;9(2 Suppl):28-35), Langley et al. (Br J Cancer. 2011 Aug 16;105(8):1107–1113), Johnson et al. (Opinion on Biological Therapy, 7(4), 449–460), Wilhelm et al. (Int J Cancer. 2011 Jul 1;129(1):245-55. Epub 2011 Apr 22), Park et al. (J Immunol. 2013 Apr 15;190(8):4103-15. Epub 2013 Mar 15), Berinstein et al. (J Transl Med 10, 156; 2012), Liu et al. (Clin Cancer Res (2017) 23 (19): 5959–5969), Ma et al. (Cancer Immunol Res (2019) 7 (3): 428–442) and NCT03396952 (Prostaglandin Inhibition and Immune Checkpoint Blockade in Melanoma; Record History 2019-05-29).
Hacohen et al. teaches a neoplasia vaccine or immunogenic composition administered in combination with other agents, such as checkpoint blockade inhibitors for the treatment of neoplasia in a subject (Abstract). Hacohen et al. teaches in claim 1, a method of treating a neoplasia in a subject in need thereof comprising administering to a subject in need thereof: (a) a neoplasia vaccine; and (b) at least one checkpoint inhibitor. They teach in claim 6 the method of treating a neoplasia in a subject in need thereof, further comprising administration of an immunomodulator or adjuvant. They also teach in claim 7 wherein the immunomodulator or adjuvant can be poly-ICLC.
Hacohen et al. teaches in Figure 1, immunization of personalized neoantigenic tumor peptides administered in combination with poly-ICLC. They also teach in Table 5, a list of clinical trials which utilized poly-ICLC in combination with cancer peptide vaccines for the treatment of various cancers. Therefore, Hacohen et al. teaches poly-ICLC as the antigen presenting cell agent recited in instant claim 1 (a). Hacohen et al. further teaches in Paragraph [00140] that neoantigenic peptide vaccines are expected to bypass central thymic tolerance thus allowing stronger anti-tumor T cell response, thus meeting the limitation of a T-cell activating vaccine of instant claim 1 part (b).
Hacohen et al. also teaches in Example 12: Phase I Study Design combining NeoVac, a Personalized NeoAntigen Cancer Vaccine, with Ipilimumab to treat high-risk renal cell carcinoma. They specifically teach in Paragraph [00497] that whole exome DNA sequence of tumor and normal tissue samples from participants were used to identify specific coding-sequence mutations that have occurred in the tumor of participants. They also teach that a well-established algorithm (netMHCpan) was used to identify mutation-containing epitopes that are predicted to bind to the MHC class I molecules of each participant and from this list of candidate mutations, 20-40 mutations were selected and prioritized for peptide preparation based on a pre-defined set of criteria (Paragraph [00497]). They further teach that twenty to forty mutations for each participant was used to design peptides, each approximately 20-30 amino acids in length whereby analysis of mutations is limited to comparison of normal and tumor sequence information for each participant (Paragraph [00498]). Hacohen et al. further teach in Paragraph [00500] that the method was intended to immunize patients with as many peptides as possible, up to a maximum of 20. Therefore, Hacohen et al. meets the limitations of the T-cell activating vaccine is a neoantigen vaccine comprising one or more neoantigens expressed in the subject’s SCT but not in the subject’s normal tissue of instant claim 1 (b), and the plurality of neoantigen peptides of instant claim 17, since renal cell carcinoma is a known solid cancerous tumor (as taught in Example 12 and Paragraphs [00497], [00498] and [00500]).
Hacohen et al. teaches in claim 9 the method of treating a neoplasia in a subject in need thereof comprising administering a neoantigen cancer vaccine and at least one checkpoint inhibitor, wherein the checkpoint inhibitor is an inhibitor of the programmed death-1 (PD-1) pathway, which is also known as an immunosuppression inhibitor, which meets the limitation of instant claim 1 (c). They teach in claims 10 and 11 that the inhibitor of the PD-1 pathway is the anti-PD1 antibody Nivolumab.
Hacohen et al. teaches in Paragraph [00210] that the tumor specific neoantigenic peptides may be utilized in combination with at least one other known therapeutic agent such as celecoxib and aspirin. As made clear by the teachings of Koki et al., celecoxib is a specific COX-2 inhibitor with anticancer properties (Title and Pg. 32 Column 2 Box Summary “Chemopreventive Effects of Celecoxib and Ibuprofen: Mammary Cancer Incidence, Tumor Burden, Tumor Volume, and Latency of Tumor Induction in a DMBA Model of Breast Cancer”). In addition, Langley et al. teaches that aspirin inhibits both Cox-1 and Cox-2 cyclooxygenase enzyme and that aspirin could have a role as an adjuvant therapy in cancer (Abstract and Pg. 1107 Column 1, Paragraph 2). Thus, Hacohen et al. teaches the COX-2 inhibitors celecoxib and aspirin can be comprised in combination with a neoantigen vaccine for the treatment of cancer as recited in instant claim 1 (d) and instant claim 5.
Hacohen et al. also teaches that promising cancer vaccine adjuvants include Toll-like receptor 9 (TLR9) agonist CpG and TLR3 ligand poly-ICLC (Paragraph [00468]). Therefore, Hacohen et al. teaches the limitation of instant claim 2 wherein the antigen presenting cell agent further comprises a Toll-like receptor agonist or an adjuvant, or a combination thereof. Hacohen et al. further teaches that immunoactive small molecules such as cyclophosphamide may act therapeutically and/or as an adjuvant when administered in combination with the cancer vaccine (Paragraph [00287]).
Hacohen et al. also teaches in claim 12, the method of treating a neoplasia in a subject in need thereof comprising administering a checkpoint inhibitor which can be an anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody. They further teach in claim 13, the anti-CTLA4 antibody is Ipilimumab or Tremelimumab. Thus, Hacohen et al. teaches the CTLA-4 inhibitors ipilimumab and tremelimumab that can be combined with a neoantigen cancer vaccine, and as such meets the limitations for claims 3 and 8.
Hacohen et al. teaches that the therapeutic agent for use in combination with the neoantigens can be the monoclonal antibody Bevacizumab (Avastin®), or regorafenib (Stivarga®), sorafenib (Nexavar®) and axitinib (Inlyta®) (Paragraph [00347]). Hacohen et al. also teaches in Paragraph [00386] that sorafenib is an approved kinase inhibitor. They further teach in Paragraph [00476] that targeted systemic agents such as inhibitors of vascular endothelial growth factor (VEGF) have provided significant clinical benefit for patients with metastatic disease. The teachings of Johnson et al. make clear that bevacizumab is a VEGF inhibitor in the form of a monoclonal antibody against VEGF having had success in enhancing immune responses and in improving the efficacy of tumor vaccines (Pg. 453 Column 1, Paragraph 1 to Pg. 454 Column 1, Paragraph 1). In addition, the teachings of Wilhelm et al. confirm that regorafenib is a multi-kinase inhibitor with potent antitumor activity (Title and Abstract). Wilhelm et al. also teaches that regorafenib inhibits VEGFR2 thereby inhibiting the proliferation of VEGF-stimulated cells (Pg. 250 Column 1, Paragraph 1). Hacohen et al. therefore teaches the limitations of instant claims 3, 6 and 9 for a method comprising a neoantigen peptide vaccine in combination with an immunosuppression inhibitor which is the VEGF inhibitor that is bevacizumab as confirmed by Johnson et al., or the multi-kinase inhibitor and VEGF inhibitor that is regorafenib as confirmed by Wilhelm et al., or the kinase inhibitor that is sorafenib as taught by Hacohen et al.
Hacohen et al. teaches in claims 40 and 41 the method further comprises administration of one or more additional agents that can be chemotherapeutic agents. Hacohen et al. also teaches in Paragraph [00347] that additional therapeutic agents administered with the neoplasia vaccine can include capecitabine. Hacohen et al. further teaches in Paragraph [00484] that in a study combining a personalized neoantigen cancer vaccine with Ipilimumab to treat high-risk renal cell carcinoma, up to 20 peptides at least 20 amino acids in length were prepared for each participant and administered together with the immune adjuvant comprising polyinosinic-polycytidylic (poly-IC). As confirmed by the teachings of Park et al., poly(I:C) is an effective Toll-like receptor adjuvant for immune responses (Title and Abstract). Therefore, Hacohen et al. teaches a method wherein a Toll-like receptor agonist that is poly(I:C) can be used as an antigen presenting cell agent.
Hacohen et al. teaches in claim 14 the method of treating or preventing a neoplasia in a subject in need thereof, wherein the subject is suffering from melanoma, sarcoma, or a cancer of the colon, breast, head and neck, lung, pancreas or prostate. Hacohen et al. also teaches in Paragraph [00157] that examples of cancers and cancer conditions that can be treated with the combination therapy of their invention include solid tumors that are recited in instant claim 15. Therefore, Hacohen et al. teaches treatment of a variety of cancer using a neoantigen vaccine in combination with adjuvants and other therapeutic agents.
Hacohen et al. does not specifically teach a method for treating a solid cancerous tumor (SCT) in a subject comprising (a) an oil in water emulsion using a mannide monooleate derivative as an emulsifier or an oil-based adjuvant composition, and (e) losartan.
However, these deficiencies are made up in the teachings of Berinstein et al. and Liu et al.
Berinstein et al. teaches that DepoVaxTM is a non-emulsion depot-forming vaccine platform with the capacity to significantly enhance the immunogenicity of peptide cancer antigens (Abstract). They teach that DepoVaxTM is a liposome-in-oil platform containing stable components that does not require creation of an emulsion that is able to simplify the use of oil-based depot vaccines in the clinic (Pg 2 column left paragraph third). They also teach that DepoVaxTM was utilized in a phase I clinical study to examine the safety and immune activating potential of DPX-0907 in advanced stage breast, ovarian and prostate cancer patients (Abstract and Pg 2 column left paragraph third).
Liu et al. teaches that use of angiotensin system inhibitors (ASI) is associated with immune activation and longer survival in nonmetastatic pancreatic ductal adenocarcinoma (Title). They teach that a reduction in cell proliferation induced by ASI is consistent with previous reports that the angiotensin II receptor type 1 (AT1R) blocker losartan inhibits the growth of tumor cells overexpressing AT1R (Pg 5965 column right paragraph first lines 6-9). They also teach that losartan decreases the recruitment and immunosuppressive effects of neutrophils and increases the recruitment of CD8-positive T cells in PDAC (Pg 5966 column left paragraph spanning lines 2-5). They further teach that in a mouse model, losartan inhibition of the renin-angiotensin-aldosterone system decreased tumor growth (Pg 5967 column left paragraph first lines 7-9) and that losartan decreased collagen, enhanced the intratumoral distribution of nanoparticles and enhanced the efficacy of nanotherapeutics in breast and pancreatic cancer mouse models (Pg 5960 column left paragraph first lines 6-9).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method for treating a solid cancerous tumor in a subject comprising administering (a) an immunomodulator or adjuvant comprising poly-ICLC; (b) a T-cell activating vaccine that is a neoantigen vaccine comprising one or more neoantigens expressed in the subject’s SCT but not in the normal tissue; (c) an immunosuppression inhibitor comprising the PD-1 antibody nivolumab; and (d) a COX-2 inhibitor that comprises aspirin, wherein in (a) to (d) are as taught by Hacohen et al., and combined with an oil-based adjuvant composition for peptide cancer antigenic vaccines as taught by Berinstein et al., and further combined with (e) losartan as taught by Liu et al. This is because Hacohen et al. teaches that (i) effective personalized neoantigen tumor peptide vaccine compositions include a strong adjuvant such as poly-ICLC to initiate an immune response (Paragraph [00140] and Figure 1) and which has been tested in various clinical trials that combine cancer vaccines with poly-ICLC (Table 5), (ii) personalized neoantigen tumor peptide vaccines can be designed by identifying mutations in the tumors of patients that are distinct from normal tissues (Paragraph [00498]), (iii) neoantigen peptide vaccine in combination with nivolumab has been studied in metastatic renal cell carcinoma (Paragraph [0052] and Figure 9), (iv) tumor specific neoantigenic peptides can be utilized in combination with aspirin which is a COX-2 inhibitor (Paragraph [00210]). Further, Koki et al. teaches that COX-2 inhibitors have potential use in the chemoprevention and chemotherapy of human tumors including colorectal cancer (Pg. 29 Column 2, Paragraph spanning and Pg. 33 Column 2, Paragraph 2), Langley et al. teaches aspirin may have a role in the adjuvant setting in colorectal cancer (Abstract, Pg. 1107 Column 1, Paragraph 2, and Pg. 1112 Column 2, Paragraph 1). In addition, Liu et al. teaches that losartan can induce immune activation in the tumor microenvironment and can decrease tumor growth (Pg 5966 column left paragraph spanning lines 2-5, Pg 5967 column left paragraph first, lines 7-9 and Pg 5965 column right paragraph first lines 6-9).
Even further, the motivation to combine a T-cell–inducing vaccine with a PD-1 antagonist mAb and a CD40 agonist mAb is also provided by the teachings of Ma et al. that studied induction of T-cell priming and TIL activation in mouse models of nonimmunogenic solid malignancies (Abstract). The motivation to combine aspirin with an immune checkpoint blockade is also provided by the teachings of NCT03396952 which studied how well pembrolizumab, ipilimumab, and aspirin work in treating patients with melanoma that has spread to other places in the body or cannot be removed by surgery (Brief Summary).
Therefore, the motivation to combine all the agents recited in instant claim 1 would be to achieve a treatment method that is personalized to patients’ tumor genetic mutations, to enhance T-cell immune response towards the personalized neoantigenic vaccine and to manipulate the susceptibility of the tumor and tumor microenvironment with a combination of agents including small molecule chemotherapeutics and large molecule antibody biologics that have been tested or have had established uses in the treatment of cancer for an enhanced effect for a method for treating a solid cancerous tumor that would otherwise be resistant to treatment.
In addition, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method for treating a solid cancerous tumor in a subject wherein the method further comprises administering (1) the antigen presenting cell agent that is the Toll-like receptor agonist of poly(I:C) as taught by Hacohen et al. and Park et al., and/or (2) the immunosuppression inhibitor further comprises a VEGF inhibitor of bevacizumab or regorafenib as taught by Hacohen et al., Johnson et al. and Wilhelm et al., and/or (iii) the immunosuppression inhibitor further comprises a multi-kinase inhibitor of regorafenib as taught by Hacohen et al. and Wilhelm et al., and/or (3) one or more chemotherapy drugs that is capecitabine as taught by Hacohen et al., because Hacohen et al. and Johnson et al. both teach that bevacizumab, a VEGF inhibitor, can be combined in a neoantigen vaccine and Johnson et al. teaches that bevacizumab enhanced the immune response and improved the efficacy of tumor vaccines (Hacohen et al. Paragraphs [00347] and [00476] and Johnson et al. Pg. 453 Column 1, Paragraph 1 to Pg. 454 Column 1, Paragraph 1), Hacohen et al. teaches regorafenib can be used in combination with a neoantigen vaccine (Paragraph [00347]) and Wilhelm et al. teaches a significant reduction in tumor area was observed in a human colorectal xenograft upon administration of regorafenib (Wilhelm et al., Abstract), Hacohen et al. teaches capecitabine can be administered in combination with a neoplasia vaccine (Paragraph [00347]), and Hacohen et al. and Park et al. teach poly(I:C) as an effective Toll-like receptor adjuvant for immune responses (Hacohen et al. Paragraph [00484] and Park et al. Title and Abstract). The motivation to combine these agents would be to achieve an enhanced effect for a method for treating a solid cancerous tumor as taught by Hacohen et al. in Paragraph [00366] as well as reasons cited above as taught by Koki et al., Langley et al., Johnson et al. and Park et al.
This is an example of (A) Combining prior art elements according to known methods to yield predictable results; and (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. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Table 1: Summary of agents and references teaching said agents described in the 103 rejection
Agents
References
(a)(i) poly-ICLC in combination with
(b) Neoplastic vaccine and
(c) one or more (immunosuppression inhibitor) checkpoint blockade inhibitor
Hacohen et al.: Abstract, claims 1, 6 and 7
(a)(i) poly-ICLC adjuvant in combination with
(b) Neoplastic vaccine
Hacohen et al.: Figure 1 and Table 5
(a)(ii) oil-based adjuvant composition DepoVaxTM in combination with
(b) peptide cancer antigenic vaccines
Berinstein et al.: Abstract and Pg 2 column left paragraph third
(b) Neoantigen cancer vaccine in combination with
(c) PD-1 antibody nivolumab
Hacohen et al.: claims 9-11
(b) Neoantigen cancer vaccine in combination with
(d) aspirin (COX-2 inhibitor)
Hacohen et al.: Paragraph [00210]
(b) Personalized plurality of neoantigen peptide cancer vaccine in combination with
(1) Ipilimumab (CTLA-4 inhibitor)
Hacohen et al.: Example 12, Paragraph [000497] and claim 12
(b) Neoantigenic cancer vaccine in combination with
(2) Toll-like receptor 9 (TLR9) agonist
Hacohen et al.: Paragraph [00468]
(b) Neoantigenic cancer vaccine in combination with
(3) cyclophosphamide
Hacohen et al.: Paragraph [00287]
(b) Neoantigen cancer vaccine in combination with
(4) monoclonal antibody Bevacizumab (Avastin®), regorafenib (Stivarga®), or sorafenib (Nexavar®)
Hacohen et al.: Paragraphs [00347] and [00386];
Supporting references: Johnson et al.: Pg. 453 Column 1, Paragraph 1 to Pg. 454 Column 1, Paragraph 1; and Wilhelm et al.: Title, Abstract and Pg. 250 Column 1, Paragraph 1
(b) Neoantigen cancer vaccine in combination with
(5) axitinib (Inlyta®)
Hacohen et al.: Paragraph [00347]
(b) Neoantigen cancer vaccine in combination with
(6) inhibitors of vascular endothelial growth factor (VEGF)
Hacohen et al.: Paragraph [00476]
(b) Neoantigen cancer vaccine in combination with
(7) capecitabine
Hacohen et al.: Paragraph [00347]
(b) Neoantigen cancer vaccine in combination with
(1) Ipilimumab (CTLA-4 inhibitor) and
(8) poly-IC (Toll-like receptor and adjuvant)
Hacohen et al.: Paragraph [00484]
(b) T-cell–inducing vaccine in combination with
(c) PD-1 antagonist mAb and
(9) CD40 agonist mAb
Ma et al.: Abstract
(d) Aspirin for cancer therapy or as an adjuvant in cancer therapy
Koki et al.: Title and Pg. 32 Column 2 Box Summary;
Langley et al.: Abstract and Pg. 1107 Column 1, Paragraph 2
(c) pembrolizumab (PD-1 inhibitor) in combination with
(d) aspirin (COX-2 inhibitor) and
(1) ipilimumab
NCT03396952: Brief Summary
(e) losartan for immune activation, tumor cell growth inhibition and tumor microenvironment modulation
Liu et al.: Title, Pg 5965 column right paragraph first lines 6-9, Pg 5967 column left paragraph first, lines 7-9 and Pg 5960 column left paragraph first lines 6-9
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yie-Chia (Tonya) Lee (Tonya) whose telephone number is (571)272-0123. The examiner can normally be reached Monday - Friday 8.30a - 5.30p Eastern Time Zone.
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, Samira Jean-Louis can be reached on 571-270-3503. 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.
/YIE-CHIA LEE (TONYA)/Examiner, Art Unit 1642
/SEAN E AEDER/Primary Examiner, Art Unit 1642