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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/4/26 has been entered.
Claims 24-29 have been added by Applicant.
Claims 13 and 15-29 are pending.
Claims 13, 15, 19, and 23 have been amended by Applicant.
Claims 13 and 15-29 are currently under examination.
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.
Rejections Withdrawn
All previous rejections are withdrawn.
New Rejections
Claim Rejections - 35 USC § 103
Claims 13 and 15-29 are rejected under 35 U.S.C. 103(a) as being unpatentable over Staunton et al (US 7,771,720 B2; 8/10/2010) in view of Kubala et al (Cancer Res, 2017, 77(13_Supp): 3061) and Suda (J Thorac Dis, 2017, 9(11): 4197-4200).
Staunton et al teaches PAI-1 protein is often expressed by cancer cells in non-invasive areas, suggesting PAI-1 plays a role in protecting tumor tissue against proteolytic degradation (lines 39-44 of column 66, in particular). Staunton et al further teaches a method of treating cancerous tumors comprising administering a compound comprising antibodies which bind and neutralize PAI-1 in combination with one or more additional therapeutic treatments (including one or a combination of anti-tumor chemotherapeutic treatments) to a cancer patient (columns 67-68, in particular). Further, one of skill in the art would recognize cancers tumors comprise tumor cells.
Staunton et al does not specifically describe a patient as expressing PD-L1. However, these deficiencies are made up in the teachings of Kubala et al and Suda.
Kubala et al teaches tumor-derived PAI-1 promotes the M2 macrophage polarization (Abstract, in particular).
Suda teaches the tumor environment comprises M1 and M2 tumor associated macrophages (page 4197) and that M2 tumor associated macrophages (M2 TAMs) express PD-L1 (Figure 2 legend).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to treat a human subject with a cancerous tumor expressing PAI-1 by performing a combined method comprising administering an effective amount of compound comprising antibodies which bind and neutralize PAI-1 in combination with one or more additional therapeutic treatments (including one or a combination of anti-tumor chemotherapeutic treatments) to the subject because Staunton et al teaches PAI-1 protein is often expressed by cancer cells and likely plays a role in protecting tumor tissue against proteolytic degradation and Staunton et al teaches a method of treating cancerous tumors comprising administering a compound comprising antibodies which bind and neutralize PAI-1 in combination with one or more additional therapeutic treatments (including one or a combination of anti-tumor chemotherapeutic treatments) to a cancer patient.
Tumors of the combined method expressing PAI-1 are predictably in a tumor microenvironment where the macrophages of the tumor microenvironment comprise M2 macrophages expressing PD-L1 because Kubala et al teaches tumor-derived PAI-1 promotes M2 macrophage polarization (Abstract, in particular), Suda teaches the tumor environment comprises M1 and M2 tumor associated macrophages (page 4197), and Suda teaches that M2 tumor associated macrophages (M2 TAMs) express PD-L1 (Figure 2 legend).
Further, recitation that the method of Staunton et al inhibits PD-L1 expression in cancer patients that happen to have immunosuppressive cells, such as M2 macrophages, that express PD-L1 is not sufficient to rebut obviousness when the combined method is expected to have a greater property of expected therapeutic benefit. See MPEP 716.02(c).
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claims 13 and 15-29 are rejected under 35 U.S.C. 103(a) as being unpatentable over Ando et al (US 10092537 B2; 10/9/18; 6/29/22 IDS), in view of Staunton et al (US 7,771,720 B2; 8/10/2010), Kubala et al (Cancer Res, 2017, 77(13_Supp): 3061), and Suda (J Thorac Dis, 2017, 9(11): 4197-4200).
Ando et al teaches a method of treating a tumor in a patient comprising administering to the patient low molecular weight inhibitors of PAI-1 (encompassed by instant claims 17-18 and 21-22) in combination with an anti-tumor agent (claim 1, in particular) that is at least one member selected from the group consisting of antimetabolites, microtubule inhibitors, antitumor antibiotics, topoisomerase inhibitors, platinum-based drugs, alkylating agents, hormone-like drugs, molecular targeted drugs, antibody drugs, cytokines, and non-specific immunostimulants (claim 4, in particular). Such alkylating agents of Ando et al include anti-tumor chemotherapeutics (column 110, in particular).
Ando et al does not specifically describe a patient as expressing PD-L1. However, these deficiencies are made up in the teachings of Staunton et al and Yadav et al.
Staunton et al teaches PAI-1 protein is often expressed by cancer cells in non-invasive areas, suggesting PAI-1 plays a role in protecting tumor tissue against proteolytic degradation (lines 39-44 of column 66, in particular). Staunton et al further teaches a method of treating cancerous tumors comprising administering inhibitors that neutralize PAI-1 in combination with one or more additional therapeutic treatments (including one or a combination of anti-tumor chemotherapeutic treatments) to a cancer patient (columns 67-68, in particular). Further, one of skill in the art would recognize cancers tumors comprise tumor cells.
Teachings of Kubala et al and Suda are discussed above.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to treat a subject with a cancerous tumor expressing PAI-1 by performing a combined method comprising administering an effective amount of low molecular weight inhibitors of PAI-1 of Ando et al in combination with anti-tumor agent of Staunton and/or Ando et al to the subject because Staunton et al teaches PAI-1 protein is often expressed by cancer cells and likely plays a role in protecting tumor tissue against proteolytic degradation, Staunton et al teaches a method of treating cancerous tumors comprising administering a compound comprising antibodies which bind and neutralize PAI-1 in combination with one or more additional therapeutic treatments (including one or a combination of anti-tumor chemotherapeutic treatments) to a cancer patient (columns 67-68, in particular) to a cancer patient, and Ando et al teaches a method of treating a tumor in a patient comprising administering to the patient low molecular weight inhibitors of PAI-1 (encompassed by instant claims 7-8) in combination with anti-tumor agent (see claims 1 and 4, in particular).
Tumors of the combined method expressing PAI-1 are predictably in a tumor microenvironment where the macrophages of the tumor microenvironment comprise M2 macrophages expressing PD-L1 because Kubala et al teaches tumor-derived PAI-1 promotes M2 macrophage polarization (Abstract, in particular), Suda teaches the tumor environment comprises M1 and M2 tumor associated macrophages (page 4197), and Suda teaches that M2 tumor associated macrophages (M2 TAMs) express PD-L1 (Figure 2 legend).
Further, recitation that the method of Staunton et al inhibits PD-L1 expression in cancer patients that happen to have immunosuppressive cells, such as M2 macrophages, that express PD-L1 is not sufficient to rebut obviousness when the combined method is expected to have a greater property of expected therapeutic benefit. See MPEP 716.02(c).
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Double Patenting
Claims 13 and 15-29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10092537 B2 in view of Staunton et al (US 7,771,720 B2; 8/10/2010), Kubala et al (Cancer Res, 2017, 77(13_Supp): 3061), and Suda (J Thorac Dis, 2017, 9(11): 4197-4200). The patent claims and the instant claims are both drawn to treating the same cancer patients by administering the same reagents. The instant claims and the patent claims differ in that the instant claims specify the cancer patients express PD-L1. Although the claims at issue are not identical, they are not patentably distinct from each other because it would have been obvious to perform the patent method wherein the patient has PAI-1 expressing tumor cells and a tumor microenvironment that comprises M2 macrophages expressing PD-L1 because Staunton et al teaches PAI-1 protein is often expressed by cancer cells and likely plays a role in protecting tumor tissue against proteolytic degradation, Staunton et al teaches a method of treating cancerous tumors comprising administering a compound comprising antibodies which bind and neutralize PAI-1 in combination with other therapeutic agents recited by the instant claims to a cancer patient, and the patent claims recite treating a tumor in a patient comprising administering to the patient low molecular weight inhibitors of PAI-1 (which, like antibodies of Staunton et al, also provides therapeutic benefit by inhibiting PAI-1) in combination with anti-tumor therapeutics encompassed by the claims; tumors of the combined method expressing PAI-1 are predictably in a tumor microenvironment where the macrophages of the tumor microenvironment comprise M2 macrophages expressing PD-L1 because Kubala et al teaches tumor-derived PAI-1 promotes M2 macrophage polarization (Abstract, in particular), Suda teaches the tumor environment comprises M1 and M2 tumor associated macrophages (page 4197), and Suda teaches that M2 tumor associated macrophages (M2 TAMs) express PD-L1 (Figure 2 legend). Said combined method is equivalent to: a method for inhibiting PD-L1 expression in a tumor or immunosuppressive cell in the patient; a method for inhibiting an immune escape of a tumor patient; a method for inhibiting exacerbation of tumor cells caused by PD-L1; and a method for enhancing an immunotherapeutic effect on tumors.
Conclusion
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/SEAN E AEDER/ Primary Examiner, Art Unit 1642
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