CTNF 18/289,836 CTNF 101787 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claim Status Claims 9-16 are cancelled. Claims 1-8 and 17-19 are pending and currently under consideration for patentability under 37 CFR 1.104. Priority This application is a 371 of PCT/US2022/072319 (filed on 05/13/2022), which claims benefit of Provisional U.S. Application Nos. 63/188,122 (filed on 05/13/2021) and 63/275,517 (filed on 11/04/2021). Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 8 and 17-19 contain subject matter which was not described Provisional U.S. Application Nos. 63/188,122 and 63/275,517; consequently, their priority date will not correspond to the provisional applications. Claims 1-7 have an effective filing date of 05/13/2021 corresponding to Provisional U.S. Application No. 63/188,122. Claims 8 and 17-19 have an effective filing date of 05/13/2022 corresponding to PCT/US2022/072319. Information Disclosure Statement The information disclosure statements filed on 04/19/2024 and 11/19/2024 have been considered. Signed copies are enclosed. 06-55 AIA Notably, the disclosure statements filed list Search Reports. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a). Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered. Specification 06-16-01 AIA The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. Claim Objections 07-29-01 AIA Claim s 17-19 are objected to because of the following informalities: they recite “the method of claim 17” and referred to itself. It should have recited “the method of claim 8” . Appropriate correction is required. Claim Rejections - 35 USC § 112(a) 07-30-01 AIA The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. 07-31-03 AIA Claim s 1 and 4-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for treating melanoma and breast cancer tumors in a subject comprising administering a therapeutically effective amount i) blocking antibodies to LAIR1 and/or (ii) losartan or DHB , does not reasonably provide enablement for treating all solid tumors in a subject comprising administering a therapeutically or prophylactically effective amount (Specification, ¶ 0095) i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370. The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444. (1) The nature or the invention Claim 1 is drawn to “a method of treating a subject who has a solid tumor, the method comprising administering to the subject a therapeutically effective amount of (i) blocking antibodies to ECM components and/or (ii) inhibitors of collagen deposition or production” (lines 1-3). Based on the specification, “therapeutic amount is one that achieves the desired therapeutic effect, e.g., boosting NK cell cytotoxicity to increase anti-tumor and anti- viral immunity in a subject. This amount can be the same or different from a prophylactically effective amount, which is an amount necessary to prevent onset of disease or disease symptoms” (¶ 0095). As such, claim 1 generally reads on treating a subject who has any type of solid tumor comprising administering a therapeutically or prophylactically effective amount of (i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production , the full scope of which is not enabled by the method as instantly claimed. (2) The state of the prior art While the state of the art is relatively high with regard to the treatment of specific cancer types, the state of the art with regard to treating cancer broadly is underdeveloped. In particular, there is no known anticancer agent that is effective against all cancer cell types. Even within a given cancer type, “[i]ntertumor and intratumor heterogeneity are important obstacles to overcome when designing the most effective therapeutic strategies for patients with cancer. The genotypic and phenotypic variability of tumors can have important consequences for diagnosis, prognosis, and treatment” (Lovly et al., Pg. e586, Integrating the Heterogeneity of Cancer in Clinical Decision Making, ¶ 1). Prior art teaches anti-cancer therapeutics could target ECM components via blocking antibodies, including anti-LAIR1 antibody (WO 2017143115 A2, Pg. 2, ¶ 2, line 1, "method of treating cancer"; Pg. 1, ¶ 4, line 3, "enhanced anti-tumor efficacy"; Pg. 5, ¶ 3, inhibitory LAIR1 antibody). LAIR1 is implicated in melanoma (WO 2017143115 A2, Pg. 3, ¶ 5) and breast cancer (Joseph et al., Cancers, 2020; Pg. 1, abstract). However, ECM components are broad, including but not limited to collagens, proteoglycans, receptors, secreted ligands, and polysaccharides; the role of such a broad class of molecules in tumorigenesis is unclear. Prior art also teaches administering inhibitors of collagen deposition or production improve breast cancer therapy efficacy, such as losartan (Diop-Frimpong et al., Proceedings of the National Academy of Sciences of the United States of America, 2011, IDS 04/19/2024, Cite No. 43; abstract) and DHB (Xiong et al. Nature Comm, 2014, IDS 04/19/2024, Cite No. 176; abstract). ECM components are broad, including but not limited to collagens, proteoglycans, receptors, secreted ligands, and polysaccharides; antibodies to ECM components would vary in target. Molecules that inhibit collagen deposition or production are also broad, including but not limited to small molecules, antibodies, and collagenases. The roles of such broad classes of molecules in tumorigenesis are unclear. According to Potter et al., cancer can be random in nature, making it incredibly difficult to prevent the formation of cancer in its entirety (Pg. 974, Introduction). In addition to spontaneous mutations, “many agents, including radiation, chemicals, and viruses” can induce cancer formation i.e. cancer does not have one cause (Cooper, Causes of Cancer, first paragraph). “Chemoprevention employs pharmaceutical agents to reduce the likelihood of disease progression… we have a multiplicity of theories of carcinogenesis that do not provide clear understanding of what is causal and, thus, an incomplete understanding of the role these agents might play in cancer. As a result, cancer chemoprevention is an almost universal failure” (Potter, Pg. 974, Introduction, paragraphs 1-3). Furthermore, there is a lack of evidence that either blocking antibodies to ECM components or inhibitors of collagen deposition or production can be administered prophylactically for the prevention of cancer. While, the specification shows how losartan and DHB increase anti-tumor response in mice with melanoma (Figs. 6-8), it does not disclose how to prevent tumors. The experiments in the specification occur post-injection of melanoma cells. The specification does not provide experiments with blocking antibodies to ECM components, instead relying on Lair1-/- mice for analysis in vivo (Figs. 4-5), the finding that NK cell cytotoxicity activity is likely suppressed by ECM components (Pg. 46-47, ¶ 0150, Example 6, “these data indicate strong NK cell killing of MHC-I-deficient tumor cells in the circulation, which is likely blocked by ECM proteins in peripheral tissues”), and the prior art to determine how ECM components affect cancer progression (the involvement of LAIR1 in breast cancer and melanoma as taught in WO 2017143115 A2 and Joseph et al.). (3) The relative skill of those in the art and (4) the predictability or unpredictability of the art, This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). While blocking antibodies to ECM components and/or inhibitors of collagen production or deposition to treat some tumors is well known by a person having ordinary skill in the art, i.e. someone with a PhD and/or MD ( the relative skill of those in the art ), the use of any blocking antibody to ECM components and/or any inhibitor of collagen production or deposition to treat any type of tumor within the scope of claim 1 is not predictable. The predictability of applying any blocking antibody to ECM components and/or any inhibitor of collagen production or deposition to any type of tumor would be low given that 1) there is not a link between ECM component and/or collagen dysfunction and all tumors, 2) blocking antibodies to ECM components and/or inhibitors of collagen production or deposition vary drastically, and 3) the instant application fails to demonstrate treatment of any type of tumor with any blocking antibody to ECM components and/or any inhibitor of collagen production or deposition commiserate to the scope of claim 1 ( the predictability or unpredictability of the art ) . (6) The amount of direction or guidance presented, (7) the presence or absence of working examples, and (8) the quantity of the experimentation The specification shows how losartan and DHB increase anti-tumor response in mice with melanoma (Figs. 6-8), post-injection of melanoma cells. The specification does not provide experiments with blocking antibodies to ECM components, instead relying on Lair1-/- mice for analysis in vivo (Figs. 4-5), the finding that NK cell cytotoxicity activity is likely suppressed by ECM components (Pg. 46-47, ¶ 0150, Example 6, “these data indicate strong NK cell killing of MHC-I-deficient tumor cells in the circulation, which is likely blocked by ECM proteins in peripheral tissues”), and the prior art to determine how ECM components affect cancer progression (the involvement of LAIR1 in breast cancer and melanoma as taught in WO 2017143115 A2 and Joseph et al., see above section regarding state of the prior art for more information). The specification does not provide any additional examples or guidance on how to use either blocking antibodies to ECM components and/or inhibitors of collagen production or deposition, other than losartan and DHB, to treat any other tumor besides melanoma ( the amount of direction or guidance presented and the presence or absence of working examples ). The amount of experimentation would not be reasonable because it would require determining which blocking antibodies to ECM components and/or inhibitors of collagen production or deposition to use to treat various tumors. Blocking antibodies to ECM components and/or inhibitors of collagen production or deposition comprise a diverse class of molecules (e.g. collagens, proteoglycans, receptors, secreted ligands, and polysaccharides ECM components that can be targeted by blocking antibodies; small molecules, antibodies, and collagenases for inhibitors of collagen production or deposition). Tumors range in pathogenesis and treatment plans. It is not routine to determine how such broad classes of molecules would treat tumors generically. Undue experimentation would be required to determine whether blocking antibodies to ECM components and/or inhibitors of collagen production or deposition would treat or prevent tumors ( the quantity of the experimentation , see MPEP 2164.06). (5) The breadth of the claims The scope of claim 1 is extremely broad; it recites multiple tumors and the use of various blocking antibodies to ECM components and/or inhibitors of collagen production or deposition that require the specification of the instant application to provide support for the entire scope of the claim. The specification fails to show that a person having ordinary skill in the art could treat all recited diseases without undue experimentation. Moreover, as described above, tumors have varying pathologies and no universal anti-cancer therapy is known. Evidence of efficacy of losartan and DHB in mice with melanoma tumors is provided in the specification, with prior art providing evidence for use in breast cancer. Prior art indicates anti-LAIR1 antibody has efficacy in melanoma and breast cancer tumors. Therefore, the method of treating melanoma and breast cancer tumors in a subject comprising administering a therapeutically effective amount i) blocking antibodies to LAIR1 and/or (ii) losartan or DHB is supported. The method of treating any type of solid tumor comprising administering a therapeutically or prophylactically effective amount of (i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production is not supported. Claim 1 is not enabled because a person having ordinary skill in the art as of the effective filing date of the application would not be able to treat any type of solid tumors comprising administering a therapeutically or prophylactically effective amount i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production with a predictability of success for the reasons outlined above. Claims 4-7 are included in this rejection as they depend on and/or incorporate claim 1. 07-31-03 AIA Claim s 2, 8, and 17-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for treating Covid-19 and herpes simplex virus in a subject comprising administering a therapeutically effective amount i) blocking antibodies to VEGF and/or ii) losartan , does not reasonably provide enablement for treating every viral infection in a subject comprising administering a therapeutically or prophylactically effective amount (Specification, ¶ 0095) i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. See 35 U.S.C. 112(a) rejection of claims 1 and 4-7 for explanation of scope of enablement and Wands factors. (1) The nature or the invention Claim 2 is drawn to “a method of treating a subject who has a viral infection, the method comprising administering to the subject a therapeutically effective amount of (i) blocking antibodies to ECM components and/or (ii) inhibitors of collagen deposition or production” (lines 1-3). Based on the specification, “therapeutic amount is one that achieves the desired therapeutic effect, e.g., boosting NK cell cytotoxicity to increase anti-tumor and anti- viral immunity in a subject. This amount can be the same or different from a prophylactically effective amount, which is an amount necessary to prevent onset of disease or disease symptoms” (¶ 0095). As such, claim 2 generally reads on treating a subject who has any viral infection comprising administering a therapeutically or prophylactically effective amount of (i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production , the full scope of which is not enabled by the method as instantly claimed. (2) The state of the prior art While the state of the art is relatively high with regard to the treatment of specific types of viral infections, the state of the art in regard to treating viral infections broadly is underdeveloped. Heise and Virgin teach viral infections vary greatly in pathology, affected by “many complex factors unique to a particular virus, a particular species, and an individual host. The interplay of these factors determines the nature of infection, whether disease occurs, and the severity of disease” (Basicmedical Key, Pg. 1, ¶ 3). For example, HIV and hepatitis C virus (HCV) are both chronic infections; however, HCV can be completely cured while HIV cannot (Heise and Virgin, Pg. 2, middle). HIV and HCV need different treatment plans consequently. Even within a given virus, prophylactic treatment can be difficult. For example, Singh states, “unique biology of HIV replication and high rate of mutations have made it harder than initially believed to come up with a preventive measure against AIDS” (Virology Journal, Pg. 6, Conclusion). A single prophylactic treatment for all viral infections is not known. Prior art teaches blocking antibodies to ECM components are implicated in the treatment of viral infections, such as anti-VEGF drug bevacizumab (Pang et al. Nat Commun, 2021, abstract, applicable to Covid-19; Hosseini and Khalili, Medical Hypotheses, 2007, abstract, applicable to herpes simplex virus). Prior art teaches inhibitors of collagen deposition are implicated in the treatment of viral infections, such as losartan (Zeinalian et al., Infect Control Hosp Epidemiol, 2020, title, applicable to Covid-19; Gardner et al., Life Sciences, 1994, abstract, applicable to herpes simplex virus). ECM components are broad, including but not limited to collagens, proteoglycans, receptors, secreted ligands, and polysaccharides; antibodies to ECM components would vary in target. Molecules that inhibit collagen deposition or production are also broad, including but not limited to small molecules, antibodies, and collagenases. The roles of such broad classes of molecules in viral infections are unclear. Furthermore, there is a lack of evidence that either blocking antibodies to ECM components or inhibitors of collagen deposition or production can be administered prophylactically for the prevention of viral infections. While, the specification shows how losartan and DHB increase anti-tumor response in mice with melanoma (Figs. 6-8), it does not disclose how to treat or prevent viral infections. The specification also does not provide experiments with blocking antibodies to ECM components. (3) The relative skill of those in the art and (4) the predictability or unpredictability of the art, This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). While blocking antibodies to ECM components and/or inhibitors of collagen production or deposition to treat some viral infections is well known by a person having ordinary skill in the art, i.e. someone with a PhD and/or MD ( the relative skill of those in the art ), the use of any blocking antibody to ECM components and/or any inhibitor of collagen production or deposition to treat any viral infection within the scope of claim 2 is not predictable. The predictability of applying any blocking antibody to ECM components and/or any inhibitor of collagen production or deposition to any viral infection would be low given that 1) there is not a link between ECM component and/or collagen dysfunction and all viral infections, 2) blocking antibodies to ECM components and/or inhibitors of collagen production or deposition vary drastically, and 3) the instant application fails to demonstrate treatment of any viral infection with any blocking antibody to ECM components and/or any inhibitor of collagen production or deposition commiserate to the scope of claim 1 ( the predictability or unpredictability of the art ) . (6) The amount of direction or guidance presented, (7) the presence or absence of working examples, and (8) the quantity of the experimentation The specification shows how losartan and DHB increase anti-tumor response in mice with melanoma (Figs. 6-8), post-injection of melanoma cells. The specification does not provide experiments with blocking antibodies to ECM components nor treatment of viral infections. The specification does not provide any examples or guidance on how to use either blocking antibodies to ECM components and/or inhibitors of collagen production or deposition to treat viral infections, instead relying on the prior art e.g. anti-VEGF drug bevacizumab and losartan in the treatment of Covid-19 and herpes simplex virus (see above section regarding state of the prior art for examples as described in Pang et al., Hosseini and Khalili, Zeinalian et al., and Gardner et al., applicable to the amount of direction or guidance presented and the presence or absence of working examples ). The amount of experimentation would not be reasonable because it would require determining which blocking antibodies to ECM components and/or inhibitors of collagen production or deposition to use to treat various viral infections. Blocking antibodies to ECM components and/or inhibitors of collagen production or deposition comprise a diverse class of molecules (e.g. collagens, proteoglycans, receptors, secreted ligands, and polysaccharides ECM components that can be targeted by blocking antibodies; small molecules, antibodies, and collagenases for inhibitors of collagen production or deposition). Viral infections range in pathogenesis and treatment plans. It is not routine to determine how such broad classes of molecules would treat viral infections generically. Undue experimentation would be required to determine whether blocking antibodies to ECM components and/or inhibitors of collagen production or deposition would treat or prevent viral infections ( the quantity of the experimentation , see MPEP 2164.06). (5) The breadth of the claims The scope of claim 2 is extremely broad; it recites multiple viral infections and the use of various blocking antibodies to ECM components and/or inhibitors of collagen production or deposition that require the specification of the instant application to provide support for the entire scope of the claim. The specification fails to show that a person having ordinary skill in the art could treat all recited diseases without undue experimentation. Moreover, as described above, viral infections have varying pathologies and no universal anti-viral therapy is known. Evidence of efficacy of losartan and DHB in mice with melanoma is provided in the specification; however, there are no experiments with blocking antibodies nor regarding viral infections. Prior art gives evidence for blocking antibodies to VEGF, losartan, and DHB efficacy in treatment of Covid-19 and herpes simplex virus. Therefore, the method of treating Covid-19 and herpes simplex virus in a subject comprising administering a therapeutically effective amount i) blocking antibodies to VEGF and/or (ii) losartan . The method of treating any type of viral infection comprising administering a therapeutically or prophylactically effective amount of (i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production is not supported. Claim 2 is not enabled because a person having ordinary skill in the art as of the effective filing date of the application would not be able to treat all viral infections comprising administering a therapeutically or prophylactically effective amount i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production with a predictability of success for the reasons outlined above. Claims 8 and 17-19 are included in this rejection as they depend on and/or incorporate claim 2 (see claim interpretation) . 07-31-03 AIA Claim 3 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA), first paragraph, because the specification, while being enabling for promoting cytotoxicity of NK cells in a subject comprising administering a therapeutically effective amount i) blocking antibodies to VEGF and/or ii) losartan or DHB , does not reasonably provide enablement for promoting cytotoxicity of NK cells in a subject comprising administering a therapeutically or prophylactically effective amount (Specification, ¶ 0095) i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production . The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. See 35 U.S.C. 112(a) rejection of claims 1 and 4-7 for explanation of scope of enablement and Wands factors. (1) The nature or the invention Claim 3 is drawn to “a method of promoting cytotoxicity of natural killer (NK) cells in a subject, the method comprising administering to the subject a therapeutically effective amount of (i) blocking antibodies to ECM components and/or (ii) inhibitors of collagen deposition or production” (lines 1-4). Based on the specification, “therapeutic amount is one that achieves the desired therapeutic effect, e.g., boosting NK cell cytotoxicity to increase anti-tumor and anti- viral immunity in a subject. This amount can be the same or different from a prophylactically effective amount, which is an amount necessary to prevent onset of disease or disease symptoms” (¶ 0095). As such, claim 3 generally reads on promoting cytotoxicity of natural killer (NK) cells in subject comprising administering a therapeutically or prophylactically effective amount of (i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production , the full scope of which is not enabled by the method as instantly claimed. (2) The state of the prior art Prior art teaches blocking antibodies to ECM components are implicated in promoting cytotoxicity of NK cells, such as anti-VEGF drug bevacizumab (Klose et al., Nat Commun, 2021, 2016, Pg. 11, column 2, last ¶, lines 1-4; see 103 section for further explanation). It is not supported that NK cell cytotoxicity can be promoted prophylactically via blocking antibodies to ECM components and/or inhibitors of collagen deposition or production. In Klose et al., treatment of cancer with bevacizumab was done after tumorigenesis. The prior art on inhibitors in collagen deposition or production with regard to promoting cytotoxicity of NK cells is lacking. The prior art focuses on inhibitors in collagen deposition or production in the context of treating cancer and viral infections (see above 112[a] rejections for more information), which may or may not affect NK cell cytotoxicity. ECM components are broad, including but not limited to collagens, proteoglycans, receptors, secreted ligands, and polysaccharides; antibodies to ECM components would vary in target. Molecules that inhibit collagen deposition or production are also broad, including but not limited to small molecules, antibodies, and collagenases. The roles of such broad classes of molecules in NK cell cytotoxicity are unclear. Furthermore, there is a lack of evidence that either blocking antibodies to ECM components or inhibitors of collagen deposition or production can be administered prophylactically to promote cytotoxicity of NK cells. While, the specification shows how losartan and DHB increase cytotoxicity of NK cells in mice with melanoma (Figs. 6-8), it does not disclose prophylactic administration. The specification also does not provide experiments with blocking antibodies to ECM components. (3) The relative skill of those in the art and (4) the predictability or unpredictability of the art, This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology". Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). While administering blocking antibodies to VEGF to promote cytotoxicity of NK cells is well known by a person having ordinary skill in the art, i.e. someone with a PhD and/or MD ( the relative skill of those in the art ), the use of any blocking antibody to ECM components and/or any inhibitor of collagen production or deposition to treat promote cytotoxicity of NK cells within the scope of claim 3 is not predictable. The predictability of applying any blocking antibody to ECM components and/or any inhibitor of collagen production or deposition to promote NK cell cytotoxicity would be low given that 1) there is not a link between all ECM component and/or collagen dysfunction to the promotion of NK cell cytotoxicity, 2) blocking antibodies to ECM components and/or inhibitors of collagen production or deposition vary drastically, and 3) the instant application fails to demonstrate promoting cytotoxicity of NK cells with any blocking antibody to ECM components and/or any inhibitor of collagen production or deposition commiserate to the scope of claim 3 ( the predictability or unpredictability of the art ) . (6) The amount of direction or guidance presented, (7) the presence or absence of working examples, and (8) the quantity of the experimentation The specification shows how losartan and DHB promote NK cell cytotoxicity in mice with melanoma (Fig. 6, NK cells interact with collagen of tumor stroma; Fig. 7, collagen deposition blocks NK cells from eliminating melanoma cells but reversed with losartan or DHB treatment; Fig. 8, tumor volume decreased with losartan or DHB treatment via cytotoxic activity of NK cells), post-injection of melanoma cells. The specification does not provide experiments with blocking antibodies to ECM components. The specification does not provide any additional examples or guidance on how to use either blocking antibodies to ECM components and/or inhibitors of collagen production or deposition to promote NK cell cytotoxicity ( the amount of direction or guidance presented and the presence or absence of working examples ). The amount of experimentation would not be reasonable because it would require determining which blocking antibodies to ECM components and/or inhibitors of collagen production or deposition to use to promote NK cell cytotoxicity. Blocking antibodies to ECM components and/or inhibitors of collagen production or deposition comprise a diverse class of molecules (e.g. collagens, proteoglycans, receptors, secreted ligands, and polysaccharides ECM components that can be targeted by blocking antibodies; small molecules, antibodies, and collagenases for inhibitors of collagen production or deposition). It is not routine to determine how such broad classes of molecules would promote NK cell cytotoxicity generically. Undue experimentation would be required to determine whether blocking antibodies to ECM components and/or inhibitors of collagen production or deposition would promote cytotoxicity of NK cells prophylactically ( the quantity of the experimentation , see MPEP 2164.06). (5) The breadth of the claims The scope of claim 3 is extremely broad; it recites promoting cytotoxicity of NK cells and the use of various blocking antibodies to ECM components and/or inhibitors of collagen production or deposition that require the specification of the instant application to provide support for the entire scope of the claim. The specification fails to show that a person having ordinary skill in the art could promote cytotoxicity of NK cells as recited in claim 3 (i.e. using any blocking antibodies to ECM components and/or any inhibitors of collagen deposition or production) without undue experimentation. Evidence of efficacy of losartan and DHB in mice with melanoma to promote cytotoxicity of NK cells is provided in the specification. However, there are no experiments in the specification with blocking antibodies to ECM components, with the prior art providing evidence for blocking antibodies to VEGF (see above section regarding state of the prior art describing Klose et al. findings). Therefore, the method of promoting cytotoxicity of NK cells in a subject comprising administering a therapeutically effective amount i) blocking antibody to VEGF and/or (ii) losartan or DHB . The method of promoting cytotoxicity of NK cells comprising administering a therapeutically or prophylactically effective amount of (i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production is not supported. Claim 3 is not enabled because a person having ordinary skill in the art as of the effective filing date of the application would not be able to promote cytotoxicity of NK cells comprising administering a therapeutically or prophylactically effective amount i) any blocking antibodies to ECM components and/or (ii) any inhibitors of collagen deposition or production with a predictability of success for the reasons outlined above. Claim Rejections - 35 USC § 112(b) 07-30-02 AIA The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 07-34-01 Claims 17-19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), 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-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 17 recites the limitations "the method of claim 17" and “the respiratory virus” in line 1. Claim 18 recites the limitations "the method of claim 17" and “the gastrointestinal virus” in line 1. Claim 19 recites the limitations "the method of claim 17" and “the viruses” in line 1. There is insufficient antecedent basis for these limitations in these claims. For the purposes of claim interpretation only, reference to “the method of claim 17” will be treated as “the method of claim 8” in claims 17-19 . Regarding claim 18, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitations following the phrase, in the instant case “coxsackieviruses and echoviruses,” are part of the claimed invention. See MPEP § 2173.05(d). For the purposes of claim interpretation only, coxsackieviruses and echoviruses will not be considered part of the claimed invention. Regarding claim 18, the phrase "coronavirus-like agents" renders the claim indefinite because it is unclear what constitutes said agent. The specification does not provide a definition for this phrase. For the purposes of claim interpretation only, “coronavirus-like agents” will be treated as coronaviruses. Claim Rejections - 35 USC § 102 07-06 AIA 15-10-15 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. 07-07-aia AIA 07-07 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. 07-12-aia AIA (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. 07-15 AIA Claim s 1, 4 and 6-7 are rejected under 35 U.S.C. 102( a)(1) and 102(a)(2 ) as being anticipated by WO 2017/143115 A2 (referred to as WO ‘115) . Regarding claims 1 and 4 , WO '115 teaches a method for treating a subject who has a solid tumor (Pg. 2, ¶ 2, line 1, "method of treating cancer"; Pg. 1, ¶ 4, line 3, "enhanced anti-tumor efficacy"), comprising administering blocking antibodies to ECM components, specifically LAIR1 (Pg. 5, ¶ 3, inhibitory LAIR1 antibody), and inhibitors of collagen deposition (Pg. 1, ¶ 4, antagonist of collagen Mab XL313). Regarding claims 6-7 , WO '115 further teaches a method for treating skin cancer, specifically melanoma (Pg. 3, ¶ 5) . 07-15 AIA Claim s 1 and 5 are rejected under 35 U.S.C. 102( a)(1) and 102(a)(2 ) as being anticipated by US 2018/0064662 A1 (referred to as US ‘662) . Regarding claims 1 and 5 , US '662 teaches a method of treating a solid tumor in a subject comprising administering metformin (Abstract, method for anti-cancer therapy in a subject with desmoplastic tumor) in combination with an inhibitor of collagen deposition, specifically losartan (¶ 0008-9, discloses a method of treating cancer comprising administering a collagen modifying agent; ¶ 0066, the collagen modifying agent is losartan), wherein "losartan reduced tumor fibrillar collagen as well as collagen-1 expression" (¶ 0211) . 07-15 AIA Claim s 2, 8, and 17-18 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Pang et al. (Efficacy and tolerability of bevacizumab in patients with severe Covid-19, Nat Commun, 2021 Feb 5;12(1):814) as evidenced by Aleem and Shah (Gastrointestinal and Hepatic Manifestations of Coronavirus, StatPearls, 2026 Jan) and Ferrara (Binding to the extracellular matrix and proteolytic processing: two key mechanisms regulating vascular endothelial growth factor action, Mol Biol Cell, 2010 Mar 1;21(5):687-90) . Regarding claim 2 , Pang et al. teach a method of treating a subject who has a viral infection, specifically coronavirus disease 2019 or Covid-19 (Pg. 1, Abstract, treating Covid-19), comprising administering blocking antibodies to ECM components (Pg. 1, Abstract, anti-VEGF drug bevacizumab; Pg. 2, column 1, ¶ 2, “blocking VEGF and the VEGF receptor [VEGFR]-mediated signaling” by employing bevacizumab). Pang et al. do not teach VEGF is an ECM component. However, Ferrara teaches VEGF can be ECM-bound while retaining bioactivity (Pg. 1, Abstract, “ECM-bound VEGF was bioactive”). VEGF as an ECM component in the form of ECM-bound VEGF would have been known to a person having ordinary skill in the art prior to the effective filing date of the application. The reference Ferrara serves as evidence of this ability of VEGF. Regarding claims 8 and 17 , Pang et al. further teach the coronavirus Covid-19 is a respiratory virus (Pg. 1, Abstract, pulmonary pathology). Regarding claim 18 , Pang et al. do not teach that the coronavirus Covid-19 is a gastrointestinal virus. However, Covid-19 is known to be gastrointestinal (Aleem and Shah, Pg. 1, Continuing Education Activity, ¶ 1, lines 2-4, “Gastrointestinal and hepatic manifestations [of Covid-19] are increasingly recognized and may occur with or without respiratory symptoms”). Covid-19 as a gastrointestinal virus would have been known to a person having ordinary skill in the art prior to the effective filing date of the application. The reference Aleem and Shah serves as evidence of this manifestation of Covid-19 . 07-15 AIA Claim s 2, 8, and 19 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Hosseini and Khalili (Therapeutic potential of bevacizumab [Avastin] in herpetic stromal keratitis [HSK], Medical Hypotheses, Volume 69, Issue 3, 2007, Pages 568-570) as evidenced by Pang et al. and Ferrara . Regarding claims 2, 8, and 19 , Hosseini and Khalili teach a method of treating a subject who has a viral infection of the eye mucosal membranes, specifically herpes simplex virus (Pg. 568, Summary, line 1, "stromal keratitis caused by herpes simplex virus"), comprising administering blocking antibodies to ECM components (Pg. 568, Summary, anti-VEGF drug bevacizumab). Hosseini and Khalili do not teach VEGF is an ECM component. However, Ferrara teaches VEGF can be ECM-bound while retaining bioactivity (Pg. 1, Abstract, “ECM-bound VEGF was bioactive”). Hosseini and Khalili do not teach bevacizumab is a blocking antibody. However, this function is an inherent characteristic of bevacizumab, inseparable from its chemical structure. MPEP 2112.01 states: “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” MPEP 2131.01(III) states: “To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence.” Pang et al. teach (Pg. 1, Abstract, anti-VEGF drug bevacizumab; Pg. 2, column 1, ¶ 2, “blocking VEGF and the VEGF receptor [VEGFR]-mediated signaling” by employing bevacizumab). The function of bevacizumab as a blocking antibody to VEGF and VEGF as an ECM component would have been known to a person having ordinary skill in the art prior to the effective filing date of the application. The references Pang et al. and Ferrara serve as evidence of these characteristics . 07-15 AIA Claim 3 is rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Klose et al. (Targeting VEGF-A in myeloid cells enhances natural killer cell responses to chemotherapy and ameliorates cachexia, Nat Commun, 7:12528, 2016) as evidenced by Ferrara, Pang et al., and Coenon et al. (Natural Killer cells at the frontline in the fight against cancer, Cell Death Dis, 15:614, 2024) . Regarding claim 3 , Klose et al. teach a method of promoting cytotoxicity of NK cells in a subject, comprising administering blocking antibodies to ECM components (Pg. 11, column 2, last ¶, lines 1-4, "treatment with a VEGF-neutralizing antibody induced… NK cell recruitment"; Pg. 4, column 2, ¶ 3, line 4, “improved treatment outcome” by reducing tumor volume). Klose et al. do not teach VEGF is an ECM component. However, Ferrara teaches VEGF can be ECM-bound while retaining bioactivity (Pg. 1, Abstract, “ECM-bound VEGF was bioactive”). Klose et al. do not teach bevacizumab is a blocking antibody. However, this function is an inherent characteristic of bevacizumab, inseparable from its chemical structure. MPEP 2112.01 states: “A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.” MPEP 2131.01(III) states: “To serve as an anticipation when the reference is silent about the asserted inherent characteristic, such gap in the reference may be filled with recourse to extrinsic evidence.” Pang et al. teach (Pg. 1, Abstract, anti-VEGF drug bevacizumab; Pg. 2, column 1, ¶ 2, “blocking VEGF and the VEGF receptor [VEGFR]-mediated signaling” by employing bevacizumab). Klose et al. does not explicitly state NK recruitment to the tumor promotes cytotoxicity. However, NK recruitment is one of the first steps for NK cells to destroy tumor cells. After NK cells search for tumor cells and recognize them as abnormal, NK become activated and the tumor cells are destroyed (Coenon et al. Pg. 1, Abstract). A person having ordinary skill in the art would recognize that induced NK recruitment promotes cytotoxicity. The function of bevacizumab as a blocking antibody to VEGF, VEGF as an ECM component, and NK recruitment to the tumor promotes cytotoxicity would have been known to a person having ordinary skill in the art prior to the effective filing date of the application. The references Pang et al., Ferrara, and Coenon serve as evidence . Double Patenting 08-33 AIA 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. 08-37 AIA Claim s 1, 4, and 6-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 35 of copending Application No. 18/014,580 (referred to as copending ‘580) in view of the disclosure of copending ‘580 (the disclosure qualifies as prior art as the patent application claims benefit to PRO 63/048,902 filed 07/07/2020). Instant claims 1, 4, and 6-7 teach a method of treating a subject who has a solid tumor comprising administering to the subject a therapeutically effective amount of blocking antibodies to ECM components ( instant claim 1 ), wherein the antibody binds LAIR1 ( instant claim 4 ) and cancer is the skin cancer melanoma ( instant claims 6-7 ). Claim 35 of copending ‘580 teaches a method of treating cancer in a subject comprising administering 1) tropisetron, ticagrelor, or cetrimonium bromide and 2) immunotherapy agent, wherein the cancer is skin cancer. Claim 35 of copending ‘580 does not teach the immunotherapy agent is a blocking antibody to LAIR1 nor the cancer is a tumor. The disclosure of copending ‘580 further teaches the immunotherapy agent is a blocking antibody that binds LAIR1 (Pg. 9, ¶ 0156, “Supplementary active compounds can also be incorporated into the compositions, e.g., for treating cancer: chemotherapy, targeted therapy and immunotherapy including immune checkpoint blockade [e.g., anti PD1, CTLA4, PD-L1, TIGIT, LAG3, TIM3 and Lairl antibody therapies]”)and the skin cancer is a tumor (Pg. 8, ¶ 138), specifically melanoma (Pg. 8, ¶ 0148). Blocking antibodies to LAIR1 and their use in treating melanoma tumors were known prior to the effective filing date of the application. In addition, both copending ‘580 and the instant application are in analogous arts (i.e. treatment of cancer with immunotherapy). Since the disclosure of copending ‘580 teaches supplementary active compounds, such as blocking antibodies to LAIR1, can be used to treat cancer, specifically melanoma tumors, there is motivation for using anti-LAIR1 blocking antibodies in a method of treating melanoma tumors. MPEP § 2141(III)(G) states a rationale that may support a conclusion of obviousness includes “[s]ome 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.” MPEP § 2143(I)(G) states this rationale should explain why “[a] person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006). The teaching, suggestion, or motivation in the prior art (i.e. supplementary active compounds such as blocking antibodies to LAIR1 can be used to treat cancer, specifically melanoma tumors, as taught in the disclosure of copending ‘580) would have led one of ordinary skill to modify the prior art reference (i.e. a method of treating cancer comprising administering an immunotherapy as taught in claim 35 of copending ‘580 ) to arrive at the claimed invention. There is a reasonable expectation of success as blocking antibodies to LAIR1 and their use in treating melanoma tumors were known prior to the effective filing date of the application. In addition, both copending ‘580 and the instant application are in analogous arts (i.e. treatment of cancer with immunotherapy). It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to use blocking antibodies to LAIR1 treat melanoma tumors as taught in the disclosure of copending ‘580 in a method of treating cancer comprising administering an immunotherapy as taught in claim 35 of copending ‘580 . This is a provisional nonstatutory double patenting rejection. Conclusion 12-151-07 AIA 07-97 12-51-07 Claim s 1-8 and 17-19 are pending. Claims 17-19 are objected to. Claims 1-8 and 17-19 are rejected. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jessica M Priest whose telephone number is (571)272-8469. The examiner can normally be reached Mon-Fri 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, Samira Jean-Louis can be reached at (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. /J.M.P./Examiner, Art Unit 1642 /SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642 Application/Control Number: 18/289,836 Page 2 Art Unit: 1642 Application/Control Number: 18/289,836 Page 3 Art Unit: 1642 Application/Control Number: 18/289,836 Page 4 Art Unit: 1642
Prosecution Insights