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 .
Election/Restrictions
Applicant’s election without traverse of:
A particular gene: serine/threonine kinase 11 (STK11 or LKB1). At least claims 1-8 and 21 read on the elected species.
A particular mutation or a particular combination of mutations selected from Tables 1-4: X155_splice from Table 1. At least claim 8 reads on the elected species.
A particular target of inhibition by the agent: leukemia inhibitory factor (LIF). At least claims 1-13 read on the elected species.
A particular gene whose expression and/or activity is increased by the agent: STK 11. At least claim 11 reads on the elected species.
A particular type of agent: antibody. At least claims 12 and 13 read on the elected species.
A particular additional anti-cancer treatment: anti-PD1 agent. At least claim 15 reads on the elected species.
A particular type of cancer: lung cancer. At least claims 16 and 17 read on the elected species.
in the reply filed on 4/20/2026 is acknowledged.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement (for example, see paragraphs [0003, 0057, 0062, 0083, 0141]; not an exhaustive list). 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference sign(s) mentioned in the description: Figure 15E (paragraph [0043]; included in “15A-15F”, though no accompanying description is present with relation to Figure 15E). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. For example, see paragraphs [0101, 0102, 0141 (pg 87 Geiger et al. ref; pg 88 Jeanson et al. ref, pg 89 Klonisch et al. ref, pg 92 Nishino et al. ref, Platt et al. ref, pg 96 Wohlhieter et al. ref)). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms “Abraxane”, “Taxotere”, “Navelbine”, and “Alimta” (paragraph [0024]), which are trade names or marks used in commerce, have been noted in this application. These terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The examples above are not an exhaustive list of unmarked trade names or marks used in commerce throughout the specification. Please carefully read through and properly notate each instance.
Claim Objections
Claim 20 objected to because of the following informalities: “wherein the bodily fluid is blood, plasma or serum” should read “wherein the bodily fluid sample is blood, plasma or serum”. This is to maintain consistent claim language with claim 18, from which claim 20 depends. Appropriate correction is required.
Applicant is advised that should claim 1 be found allowable, claim 3 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112b - Indefiniteness
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.
Claims 8, 11, and 15 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 8 is unclear over the recitation of the limitation requiring one or more mutations “selected from the mutations listed in Tables 1-4”. MPEP 2173.05(s) provides guidance regarding references to figures or tables in claims:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant's convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993)
In the instant case, the rejection may be addressed by referencing the names of the mutations, as consonant with the disclosure, in the text of the claims.
Claim 11 contains the limitation “wherein the agent inhibits LIF/LIFR-mediated signaling by increasing the expression and/or activity of STK11” (consonant with the election). It is unclear how this would work if the requirement for treatment is that STK11 has a mutation that makes it amenable to treatment with said anti-LIF/LIFR agent. For example, if said mutation is a loss-of-function mutation, then claim 11 would not be possible to achieve.
Claim 15: A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 15 recites the broad recitation paclitaxel, albumin-bound paclitaxel, docetaxel, gemcitabine, vinorelbine, etoposide, and pemetrexed, and the claim also recites Taxol, nab-paclitaxel and Abraxane, Taxotere, Gemzar, Navelbine, VP-16, and Alimta which are the narrower statements of the ranges/limitations, respectively. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. In amending this claim, Applicant is cautioned against solely using trademarks or trade names as limitations in the claim.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 4 is rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas (e.g.: mental processes) and a natural phenomenon without significantly more.
The claim(s) recite(s) methods of determining that a subject having cancer will likely benefit from a treatment comprising an agent that modulates leukemia inhibitory factor (LIF)/leukemia inhibitory factor receptor (LIFR)-mediated signaling with a step of detecting one or more mutations in a sample from the subject. The claims are thus directed to the assessment of collected data, which is an abstract idea that is a mental process (e.g.: MPEP 2106.04(a (2)(III)(A)); it is the observation and evaluation of information to reach a judgment or conclusion, as set forth in claim 4. Where the evaluation of data to reach a conclusion is based in the asserted correlation between a mutation and the likely response of a subject to a particular treatment, such an association is accepted part of how a biological organism functions (i.e.: genotype:phenotype relationships), and as such this element of the claims is a natural phenomenon (e.g.: MPEP 2106.04(b)(I)). This judicial exception is not integrated into a practical application because there are no practical steps related to the determination of a likely response in the subject with cancer. There are no additional steps of the claims that are directed to applying or using the judicial exception(s) noted above (e.g.: MPEP 2106.04(d)(I)). The claims end with an asserted association between a genotype and the likely response to a treatment, which is an abstract idea (as noted above).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims only broadly recite steps of detecting one or more mutations in STK11/LKB1 (as consonant with the election). However, such steps were well understood, routine and convention in the prior art (e.g.: MPEP 2106.05(d)). For example: Chopra and Gleeson (referenced below) teach sequencing STK11/LKB1 to detect mutation status.
For these reasons claim 4 is rejected under 35 USC 101 as directed to subject matter that is not significantly more than a judicial exception.
Claim Interpretation
Claim 18 contains the limitation “wherein the subject sample is a tumor sample or a bodily fluid sample comprising circulating tumor DNA (ctDNA)”. This is interpreted to mean that the tumor sample does not comprise ctDNA, only the bodily fluid sample comprises ctDNA. Additionally, because the language of claim 18 is “tumor sample or bodily fluid sample”, any further limitation of bodily fluid sample (such as in claim 20), would be automatically rejected by any reference which teaches that the subject sample is a tumor sample given that tumor sample and bodily fluid sample are in the alternative.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2, 7, 9-10, 12-13, and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Chopra (Chopra et al., US 2011/0257167 A1) in view of Suarez ‘898 (Suarez et al., WO 2019/243898 A2), Koyama (Koyama et al., Cancer Research 2016; cited on IDS of 9/10/2024), and Wang (Wang et al., Oncology Letters 2021).
Claims 1 and 2: Chopra teaches a method for treating a subject with cancer wherein the subject comprises a mutation in LKB1 (STK11) and then administering a treatment for the cancer based on the presence of said mutation (paragraph [0013]).
Chopra does not teach that the treatment administered is an agent that modulates LIF/LIFR-mediated signaling. However, treatment of cancers with an agent that modulates LIF/LIFR-mediates signaling is known in the art, as taught by Suarez ‘898.
Suarez ‘898 teaches a method of administering an anti-LIF antibody to individuals with cancer that are most likely to respond to said antibody (paragraph [0004]). Suarez ‘898 teaches determining the levels of certain biomarkers to indicate that LIF-inhibition would be a successful treatment, including immunosuppressive/immunomodulatory biomarkers such as chemokines and cytokines (paragraph [0101]) and increased levels of phosphorylated STAT3 (paragraph [0102]). The anti-LIF antibody inhibits LIF biological activity and thus “modulates” LIF/LIFR-mediated signaling (paragraph [0118]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Chopra to treat STK11/LKB1-mutated cancers with an anti-LIF antibody, as taught by Suarez ‘898. One would be motivated to treat an STK11/LKB1-mutated cancer with an anti-LIF antibody given the teaching by Koyama that STK11/LKB1-deficient lung tumors exhibit elevated levels of cytokines and chemokines (Results - Lkb1-deficient tumor cells stimulate neutrophil recruitment through the production of cytokines and chemokines), a biomarker which Suarez ‘898 teaches is a good indicator of successful treatment of a cancer with an anti-LIF antibody. Chopra teaches using their methodology to treat non-small cell lung carcinoma (paragraph [0013]), a cancer that is known in the art to have elevated levels of LIF expression, as taught by Wang (Results - LIF is overexpressed in NSCLC, specifically in the adenocarcinoma subtype). Given that Suarez ‘898 teaches that a combination of LIF overexpression and increased levels of chemokines and cytokines are good indicators of successful treatment with an anti-LIF antibody, one would have a reasonable expectation of success in treating non-small cell lung cancer with STK11/LKB1 mutations.
Claim 7: Chopra teaches that the one or more mutations are loss-of-function mutations or copy loss mutations (paragraph [0079]).
Claims 9 and 10: Suarez ‘898 teaches that the agent inhibits LIF/LIFR-mediated signaling by inhibiting the activity of LIF (paragraph [0118]).
Claims 12 and 13: Suarez ‘898 teaches that the agent is an antibody, specifically an anti-LIF antibody (Abstract, paragraphs [0004, 0118]).
Claims 16 and 17: Chopra teaches that the method is used for treating lung cancer, specifically non-small cell lung cancer (paragraph [0013]).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Chopra (Chopra et al., US 2011/0257167 A1) in view of Suarez ‘898 (Suarez et al., WO 2019/243898 A2), Koyama (Koyama et al., Cancer Research 2016; cited on IDS of 9/10/2024), and Wang (Wang et al., Oncology Letters 2021) as applied to claims 1-2, 7, 9-10, 12-13, and 16-17 above, and further in view of Gleeson (Gleeson et al., Journal of Thoracic Oncology) and Donnelly (Donnelly et al., Carcinogenesis 2021).
The teachings of Chopra in view of Suarez ‘898, Koyama, and Wang are detailed above. Relevant to the instantly rejected claim, Chopra in view of Suarez ‘898, Koyama, and Wang teach treating STK11/LKB1-deficient tumors (loss of function or copy number loss) with an anti-LIF antibody.
Chopra in view of Suarez ‘898, Koyama, and Wang do not teach that the mutation in STK11/LKB1 is a splice site mutation of c.465-2A>T. However, presence of this mutation in lung adenocarcinomas and its effect on STK11/LKB1 function is known in the art as taught by Gleeson and Donnelly.
Gleeson teaches detecting c.465-2A>T mutation in LKB1 in an adenocarcinoma sample taken from patients diagnosed with a primary lung adenocarcinoma (Materials and Methods, Table 2).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Chopra in view of Suarez ‘898, Koyama, and Wang to detect the splice site mutation of c.465-2A>T as taught by Gleeson. One would be motivated to detect this mutation given the teaching by Gleeson that this mutation was present in a metastatic tumor that was sourced from a lung adenocarcinoma, indicating association with metastasis. Additionally, Donnelly teaches that point mutations at this specific splice acceptor site (c.465-2A, V4 in Donnelly), results in the creation of an STK11 protein with an in-frame 14 amino acid deletion (Results – STK11 splice-site variant assessment). Donnelly teaches that this deletion generates an unstable protein, and leads to no detectable presence of STK11 protein in cells expressing this variant (Results – STK11 splice-site variant assessment, Figure 4B). One would have a reasonable expectation of successfully treating a cancer patient with this mutation given that the splice site variant leads to a loss of function of the STK11 protein and thus is consistent with the methodology of Chopra in view of Suarez ‘898, Koyama, and Wang.
Claims 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Chopra (Chopra et al., US 2011/0257167 A1) in view of Suarez ‘898 (Suarez et al., WO 2019/243898 A2), Koyama (Koyama et al., Cancer Research 2016; cited on IDS of 9/10/2024), and Wang (Wang et al., Oncology Letters 2021) as applied to claims 1-2, 7, 9-10, 12-13, and 16-17 above, and further in view of Suarez ‘903 (Suarez et al., WO 2019/197903 A1).
The teachings of Chopra in view of Suarez ‘898, Koyama, and Wang are detailed above. Relevant to the instantly rejected claim, Chopra in view of Suarez ‘898, Koyama, and Wang teach treating STK11/LKB1-deficient tumors (loss of function or copy number loss) with an anti-LIF antibody.
Chopra in view of Suarez ‘898, Koyama, and Wang do not teach administering an additional anti-cancer treatment, or that said additional anti-cancer treatment is anti-PD1. However, administration of anti-LIF antibody with an anti-PD1 agent is known in the art, as taught by Suarez ‘903.
Suarez ‘903 teaches treating cancer using a combination of LIF-binding agents (anti-LIF antibodies) and PD-1 axis inhibitors (Abstract and paragraph [0004]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Chopra in view of Suarez ‘898, Koyama, and Wang to additional treat with an anti-PD1 agent as taught by Suarez ‘903. One would be motivated to do so given the assertion by Suarez ‘903 that that “these combinations exhibit a surprising synergy when compared to either anti-LIF antibodies or PD-1 axis inhibitors alone” (paragraph [0004]). One would have a reasonable expectation of success given that Suarez ‘903 teaches that this treatment can be used to treat non-small cell lung cancer (paragraph [0005, 0017]).
Claims 3, 6, and 18-21 are rejected under 35 U.S.C. 103 as being unpatentable over Chopra (Chopra et al., US 2011/0257167 A1) in view of Suarez ‘898 (Suarez et al., WO 2019/243898 A2), Koyama (Koyama et al., Cancer Research 2016; cited on IDS of 9/10/2024), and Wang (Wang et al., Oncology Letters 2021).
Claims 3 and 6: Chopra teaches a method for treating a subject with cancer in which one or more mutations in LKB1 (STK11) are detected in a sample from the subject and then a treatment for the cancer based on the presence of said one or more mutations is administered to the subject (paragraph [0013]).
Chopra does not teach that the treatment administered is an agent that modulates LIF/LIFR-mediated signaling. However, treatment of cancers with an agent that modulates LIF/LIFR-mediates signaling is known in the art, as taught by Suarez ‘898.
Suarez ‘898 teaches a method of administering an anti-LIF antibody to individuals with cancer that are most likely to respond to said antibody (paragraph [0004]). Suarez ‘898 teaches determining the levels of certain biomarkers to indicate that LIF inhibition would be a successful treatment, including immunosuppressive/immunomodulatory biomarkers such as chemokines and cytokines (paragraph [0101]) and increased levels of phosphorylated STAT3 (paragraph [0102]). The anti-LIF antibody inhibits LIF biological activity and thus “modulates” LIF/LIFR-mediated signaling (paragraph [0118]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Chopra to treat STK11/LKB1-mutated cancers with an anti-LIF antibody, as taught by Suarez ‘898. One would be motivated to treat an STK11/LKB1-mutated cancer with an anti-LIF antibody given the teaching by Koyama that STK11/LKB1-deficient lung tumors exhibit elevated levels of cytokines and chemokines (Results - Lkb1-deficient tumor cells stimulate neutrophil recruitment through the production of cytokines and chemokines), a biomarker which Suarez ‘898 teaches is a good indicator of successful treatment of a cancer with an anti-LIF antibody. Chopra teaches using their methodology to treat non-small cell lung carcinoma (paragraph [0013]), a cancer that is known in the art to have elevated levels of LIF expression, as taught by Wang (Results - LIF is overexpressed in NSCLC, specifically in the adenocarcinoma subtype). Given that Suarez ‘898 teaches that a combination of LIF overexpression and increased levels of chemokines and cytokines are good indicators of successful treatment with an anti-LIF antibody, one would have a reasonable expectation of success in treating non-small cell lung cancer with STK11/LKB1 mutations.
Claim 18 and 20: Chopra teaches that the subject sample is a tumor sample (paragraph [1174]). Because Chopra teaches that the subject sample is a tumor sample, any further limitations of a bodily fluid sample are automatically rejected (claim 20; see Claim Interpretation above).
Claim 19: Suarez teaches that the subject sample can be a tumor biopsy (paragraph [0007]).
Claim 21: Chopra teaches detecting the STK11/LKB1 mutations via sequencing (paragraph [0014]).
Claims 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Chopra (Chopra et al., US 2011/0257167 A1) in view of Suarez ‘898 (Suarez et al., WO 2019/243898 A2), Koyama (Koyama et al., Cancer Research 2016; cited on IDS of 9/10/2024), and Wang (Wang et al., Oncology Letters 2021).
Claims 4 and 5: Chopra teaches a method for treating a subject with cancer in which one or more mutations in LKB1 (STK11) are detected in a sample from the subject and then a treatment for the cancer based on the presence of said one or more mutations is administered to the subject (paragraph [0013]).
Chopra does not teach that the treatment administered is an agent that modulates LIF/LIFR-mediated signaling and that said mutations identify the subject as likely to benefit from said treatment. However, treatment of cancers with an agent that modulates LIF/LIFR-mediates signaling is known in the art, as taught by Suarez ‘898.
Suarez ‘898 teaches a method of administering an anti-LIF antibody to individuals with cancer that are most likely to respond to said antibody (paragraph [0004]). Suarez ‘898 teaches determining the levels of certain biomarkers to indicate that LIF inhibition would be a successful treatment, including immunosuppressive/immunomodulatory biomarkers such as chemokines and cytokines (paragraph [0101]) and increased levels of phosphorylated STAT3 (paragraph [0102]). The anti-LIF antibody inhibits LIF biological activity and thus “modulates” LIF/LIFR-mediated signaling (paragraph [0118]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Chopra to treat STK11/LKB1-mutated cancers with an anti-LIF antibody, as taught by Suarez ‘898. One would be motivated to treat an STK11/LKB1-mutated cancer with an anti-LIF antibody given the teaching by Koyama that STK11/LKB1-deficient lung tumors exhibit elevated levels of cytokines and chemokines (Results - Lkb1-deficient tumor cells stimulate neutrophil recruitment through the production of cytokines and chemokines), a biomarker which Suarez ‘898 teaches is a good indicator of successful treatment of a cancer with an anti-LIF antibody. Chopra teaches using their methodology to treat non-small cell lung carcinoma (paragraph [0013]), a cancer that is known in the art to have elevated levels of LIF expression, as taught by Wang (Results - LIF is overexpressed in NSCLC, specifically in the adenocarcinoma subtype). Given that Suarez ‘898 teaches that a combination of LIF overexpression and increased levels of chemokines and cytokines are good indicators of successful treatment with an anti-LIF antibody, one would have a reasonable expectation of success in treating non-small cell lung cancer with STK11/LKB1 mutations.
Double Patenting
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.
U.S. Patent No. 11,944,615
Although the claims are not identical, they are not patentably distinct from each other because both sets of claims are drawn to the same limitations. Any additional limitations of the ‘615 claims are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1-7, 9, 10, and 12-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 10-11 of U.S. Patent No. 11,944,615 in view of Suarez ‘898 (Suarez et al., WO 2019/243898 A2), Koyama (Koyama et al., Cancer Research 2016; cited on IDS of 9/10/2024), and Wang (Wang et al., Oncology Letters 2021).
Claim 1: The claims of ‘615 teach treating a cancer in a patient that is deficient for LKB1. The claims of ‘615 do not teach that the treatment administered is an agent that modulates LIF/LIFR-mediated signaling. However, treatment of cancers with an agent that modulates LIF/LIFR-mediates signaling is known in the art, as taught by Suarez ‘898.
Suarez ‘898 teaches a method of administering an anti-LIF antibody to individuals with cancer that are most likely to respond to said antibody (paragraph [0004]). Suarez ‘898 teaches determining the levels of certain biomarkers to indicate that LIF-inhibition would be a successful treatment, including immunosuppressive/immunomodulatory biomarkers such as chemokines and cytokines (paragraph [0101]) and increased levels of phosphorylated STAT3 (paragraph [0102]). The anti-LIF antibody inhibits LIF biological activity and thus “modulates” LIF/LIFR-mediated signaling (paragraph [0118]).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of ‘615 to treat STK11/LKB1-mutated cancers with an anti-LIF antibody, as taught by Suarez ‘898. One would be motivated to treat an STK11/LKB1-mutated cancer with an anti-LIF antibody given the teaching by Koyama that STK11/LKB1-deficient lung tumors exhibit elevated levels of cytokines and chemokines (Results - Lkb1-deficient tumor cells stimulate neutrophil recruitment through the production of cytokines and chemokines), a biomarker which Suarez ‘898 teaches is a good indicator of successful treatment of a cancer with an anti-LIF antibody. The claims of ‘615 teaches using their methodology to treat lung cancer (claim 4), a cancer that is known in the art to have elevated levels of LIF expression, as taught by Wang (Results - LIF is overexpressed in NSCLC, specifically in the adenocarcinoma subtype). Given that Suarez ‘898 teaches that a combination of LIF overexpression and increased levels of chemokines and cytokines are good indicators of successful treatment with an anti-LIF antibody, one would have a reasonable expectation of success in treating lung cancer with STK11/LKB1 mutations that are loss-of function or copy number loss (LKB1-deficient).
Claims 9 and 10: Suarez ‘898 teaches that the agent inhibits LIF/LIFR-mediated signaling by inhibiting the activity of LIF (paragraph [0118]).
Claims 12 and 13: Suarez ‘898 teaches that the agent is an antibody, specifically an anti-LIF antibody (Abstract, paragraphs [0004, 0118]).
Claim 17: Suarez ‘898 teaches administering an anti-LIF antibody to non-small cell lung cancer (paragraph [0002, 0033]).
Claim 18-20: Suarez ‘898 teaches that a biological sample from a patient can be a tumor biopsy (a type of tumor sample; paragraph [0007]).
Claims 8 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 10-11 of U.S. Patent No. 11,944,615 in view of Suarez ‘898 (Suarez et al., WO 2019/243898 A2), Koyama (Koyama et al., Cancer Research 2016; cited on IDS of 9/10/2024), and Wang (Wang et al., Oncology Letters 2021) as applied to claims 1-7, 9, 10, and 12-20 above, and further in view of Gleeson (Gleeson et al., Journal of Thoracic Oncology) and Donnelly (Donnelly et al., Carcinogenesis 2021).
The teachings of ‘615 in view of Suarez ‘898, Koyama, and Wang are detailed above. Relevant to the instantly rejected claim, ‘615 in view of Suarez ‘898, Koyama, and Wang teach treating STK11/LKB1-deficient tumors (loss of function or copy number loss) with an anti-LIF antibody.
‘615 in view of Suarez ‘898, Koyama, and Wang do not teach that the mutation in STK11/LKB1 is a splice site mutation of c.465-2A>T that is discovered through sequencing. However, presence of this mutation in lung adenocarcinomas and its effect on STK11/LKB1 function is known in the art as taught by Gleeson and Donnelly.
Gleeson teaches detecting c.465-2A>T mutation in LKB1 via sequencing in an adenocarcinoma sample taken from patients diagnosed with a primary lung adenocarcinoma (Materials and Methods, Table 2).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of ‘615 in view of Suarez ‘898, Koyama, and Wang to detect the splice site mutation of c.465-2A>T as taught by Gleeson. One would be motivated to detect this mutation given the teaching by Gleeson that this mutation was present in a metastatic tumor that was sourced from a lung adenocarcinoma, indicating association with metastasis. Additionally, Donnelly teaches that point mutations at this specific splice acceptor site (c.465-2A, V4 in Donnelly), results in the creation of an STK11 protein with an in-frame 14 amino acid deletion (Results – STK11 splice-site variant assessment). Donnelly teaches that this deletion generates an unstable protein, and leads to no detectable presence of STK11 protein in cells expressing this variant (Results – STK11 splice-site variant assessment, Figure 4B). One would have a reasonable expectation of successfully treating a cancer patient with this mutation given that the splice site variant leads to a loss of function of the STK11 protein and thus is consistent with the methodology of ‘615 in view of Suarez ‘898, Koyama, and Wang.
.
Co-pending Application No. 18/417,928
Although the claims are not identical, they are not patentably distinct from each other because both sets of claims are drawn to the same limitations. Any additional limitations of the ‘928 claims are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection.
Claims 1-7, 9-10, 12-13, 16-17, and 18-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 8 of copending Application No. 18/417,928 in view of Suarez ‘898 (Suarez et al., WO 2019/243898 A2), Koyama (Koyama et al., Cancer Research 2016; cited on IDS of 9/10/2024), and Wang (Wang et al., Oncology Letters 2021) according to citations and rationales provided above.
Claim 7: Koyama teaches LKB1 deficiency (loss of function or copy number loss) in non-small cell lung cancer, specifically wherein this deficiency leads to an increase in chemokines and cytokines (Results - Lkb1-deficient tumor cells stimulate neutrophil recruitment through the production of cytokines and chemokines).
Claims 8 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 8 of copending Application No. 18/417,928 in view of Suarez ‘898 (Suarez et al., WO 2019/243898 A2), Koyama (Koyama et al., Cancer Research 2016; cited on IDS of 9/10/2024), and Wang (Wang et al., Oncology Letters 2021) as applied to claims 1-7, 9-10, 12-13, 16-17, and 18-20 above, and further in view of Gleeson (Gleeson et al., Journal of Thoracic Oncology) and Donnelly (Donnelly et al., Carcinogenesis 2021) according to citations and rationales provided above.
Claims 14-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 8 of copending Application No. 18/417,928 in view of Suarez ‘898 (Suarez et al., WO 2019/243898 A2), Koyama (Koyama et al., Cancer Research 2016; cited on IDS of 9/10/2024), and Wang (Wang et al., Oncology Letters 2021) as applied to claims 1-7, 9-10, 12-13, 16-17, and 18-20 above, and further in view of Suarez ‘903 (Suarez et al., WO 2019/197903 A1) according to citations and rationales provided above.
Conclusion
No claims are allowed.
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/KAILEY ELIZABETH CASH/ Examiner, Art Unit 1683
/ANNE M. GUSSOW/ Supervisory Patent Examiner, Art Unit 1683
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