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 Group I in the reply filed on 06/09/2026 is acknowledged.
Claims 1, 2, 4, 6-8, 10, 13, 15, 17-18, 21-22, 24-25, 27-28, 30, 33 and 35 are pending.
Claims 25, 27-28, 30, 33 and 35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/10/2026.
Claims 1, 2, 4, 6-8, 10, 13, 15, 17-18, 21-22, and 24 are pending and are currently under consideration.
Information Disclosure Statement
The IDS filed 03-26-2025 was considered except for reference 13 as the title for this Clinical Trial appears incorrect. Note that the titles for reference 12 and 13 are identical.
Claim Objections
Claims 7, 13 and 15 are objected to because of the following informalities: The claims are missing the word “of” following recitation of “The method”. Appropriate correction is requested.
Claim Rejections - 35 USC § 112
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.
Regarding claim 21, the item within the parenthetical expression “(LPS)”, renders the claim indefinite because it is unclear whether the limitation within the expression is merely exemplary (similar to “such as” language) or is part of the claimed invention. See MPEP § 2173.05(d).
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.
Claims 1, 4, 6-8, 10, 13, 15, 21-22, and 24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Regarding claim 1, the claim recites a method of contacting a patient sample with an innate immune agonist; and measuring the level of at least one inflammatory cytokine wherein the level of inflammatory cytokine production is indicative of responsiveness of the patient to an immunotherapy, wherein the patient has cancer and the immunotherapy comprises an anti-cancer immunotherapeutic.
The step of observing a level of inflammatory cytokine production that is indicative of a responsiveness of the patient to an immunotherapy is a natural correlation that can be performed mentally. Thus, the claim is drawn to a judicial exception; a natural phenomenon in concert with an abstract idea. (Step 2A Prong 1: Yes).
This judicial exception is not integrated into a practical application because the claim’s function is to observe some level of cytokine production that might qualify a cancer patient for immunotherapy; there is no application of this observing step. Also, as in MPEP 2106.04(d), the claim does not use the judicial exception to improve a computer or some other technology, does not apply the judicial exception for a particular treatment, does not perform the data analysis using a particular machine, and does not use the judicial exception to transform one article to another. Further, the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because, in addition to the considerations in Step 2A Prong 2, the “contacting” and “measuring” steps are well-understood, routine, conventional activity. Thus, claim 1 is rejected as being directed to a judicial exception.
Claims 4 and 6 merely exemplify the types of immunotherapies that could be applied should the cancer patient qualify for the treatment, and thus further constitutes a mental step that does not use the judicial exception to transform one article to another.
Claims 7-8, 10, 13 tell the practitioner what types of cytokines to measure and what types of innate immune agonists are to be used for the contacting step and are thus mere gathering steps. As such, these steps represent insignificant extra solution activity because it is mere data gathering. MPEP 2106.05(g) states that the courts have found the following to be mere data gathering: performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989); and determining the level of a biomarker in blood, Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. at 79, 101 USPQ2d at 1968. Thus, in these claims, as in the prior cases, the non-mathematical steps of the method merely perform laboratory manipulation on samples from individuals. (Step 2A Prong 2: no, not integrated into a practical application).
Claim 15 merely clarifies the judicial exception (the levels of inflammatory cytokines) to observing an increase and thus is similar to the rationale in paragraph 13 above.
Similar to paragraph 16 above, claims 21-22, and 24 further define what type of cancer is observed, which immune agonist is used, and which inflammatory cytokine is measured; all of which are data gathering steps that do not integrate the judicial exception into a practical application. See MPEP 2106.04(d).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-2, 4, 6, 7-8, 10, 13, 15, 17-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boyle et al. (US20140154712A1, published 06-05-2014) in view of Weinschenk et al. (US 9389235, applicant’s IDS) and Hunter, Philip (“Vaccines against Cancer”, EMBO reports, Vol. 15. No. 5, 2014).
As to claim 1, Boyle et al. teach (see claim 1 of Boyle et al.) a method comprising contacting a patient sample [0098] with an “innate immune agonist”, measuring the level of at least one inflammatory cytokine (referred to as immune effector molecules in Boyle et al.) wherein the level of inflammatory cytokine production is indicative of responsiveness of the patient during a cancer therapy, wherein the patient has cancer. Specifically, Boyle et al. teach [0175] that the method may be used in the diagnosis and staging of a disease. The present disclosure may also be used to monitor the progression of a condition and to monitor whether a particular treatment is effective or not. In particular, the method can be used to monitor immunosuppression following surgery, cancer therapy or medication or exposure to toxicants. Further, [0017] the magnitude of the cell-mediated immune response detected in the assay can be correlated to the disease state, progression and/or severity.
As to claims 7 and 13, Boyle et al. teach [0072] that the inflammatory cytokines (e.g. effector molecules) may be any of a range of molecules which are produced in response to cell activation or stimulation by an antigen. Although an interferon (IFN) such as IFN-γ is a particularly useful immune effector molecule, others include a range of cytokines such as interleukins (IL), e.g. IL-2, IL-4, IL-6, IL-6 (CXCL8), IL-10, IL-12, IL-13, IL-16 (LCF) or IL-17, IL-1α (IL-1F1), IL-1β (IL-1F2), IL-1rα (IL-1F3). Tumor Necrosis Factor alpha (TNF-α), Transforming Growth Factor beta (TGF-β), a Colony Stimulating Factor (CSF) such as Granulocyte (G)-CSF or Granulocyte Macrophage (GM)-CSF, complement component 5a (C5a), Groα (CXCL1), sICAM-1 (CD54), IP-10 (CXCL10), I-TAC (CXCL11), MCP-1 (CCL2), MIF (GIF). MIP-1α (CCL3), MIP-1β (CCL4), RANTES (CCL5) or MIG (CXCL9).
As to claims 8-10, Boyle et al. teach [0011 and claims] that the innate immune agonist is a toll-like receptor agonist (a pattern recognition receptor).
Boyle et al. do not appear to teach that the particular cancer therapy that a patient could qualify for or is subjected to is “an immunotherapy” (Claims 1 and 2) wherein the immunotherapy could be “an immune checkpoint inhibitor, a vaccine, an adjuvant, a cytokine, human cell therapy, a micro-organism, or a virus (Claim 4) or wherein the immunotherapy encompasses an oncolytic virus (Claims 6, 17-18). Boyle et al. also does not specifically teach that when the level of inflammatory production is increased it is indicative of immune proficiency to respond to a cancer immunotherapy (Claims 2 and 15).
Boyle et al., however also teaches [0195] treatment of a subject having cancer comprising contacting a sample from a cancer patient with an antigen and a limiting amount of TLR agonist and measuring the presence or elevation in the level of an immune effector molecule from T-cells wherein the presence or level of the immune effector molecule is indicative of the level of cell-mediated responsiveness of the subject which is indicative of the presence, absence, level or state of the condition or disorder and then treating the condition or disorder.
In summary, Boyle et al. teaches the primary steps of Claim 1 including the contacting step and the measuring step- all from a patient that has cancer. What is lacking is the type of therapy that a cancer patient could be receiving as Claim 1 does not require that the patient be actively undergoing therapy, just that the therapy to be considered is “immunotherapy”.
Weinschenk et al. (US 9389235, applicant’s IDS, for specific teaches refer to PG-PUB, US20140234347) teach [0025] a similar methodology by providing a method for predicting an effect of an immunotherapy in a cancer patient, comprising a) determining the level of at least one marker in a sample from said cancer patient, wherein a higher (or increased) level of the marker compared to the median of a given cancer patient population is indicative for a beneficial effect of an immunotherapy for said patient. Similar to the markers in current claim 7, the markers [0043] can be chemokines such as CXCL13 where elevated levels are associated with metastasis. The immunotherapy [0058-0059] can be a vaccine, an adjuvant, human cell therapy, cytokines [0059].
Other immunotherapies for treating cancer are reviewed by Hunter, Philip (EMBO reports, Vol. 15. No. 5, 2014) where other modalities included the use of oncolytic viruses such as the herpes virus (page 487). The infectious agent was at first regarded as a complicating factor but then became a potential vaccine target. In fact, pathogens make easier targets because they elicit a stronger immune response and avoid the issue of having to break the immune system’s tolerance to self-antigens in tumors. Prophylactic HPV vaccines have been given to teenage girls for some years now and significantly reduced the incidence of cervical cancer. Another therapeutic vaccine for prostate cancer—ProstVac, developed by the Denmark-based biotech company Bavarian Nordic—is made by adding prostate-specific antigen to the vaccinia virus (encompasses a derivative of the poxvirus) that was commonly used for smallpox vaccines, with the objective of stimulating an immune response against the tumor.
First, up to at least year 2014 (the publication date of Boyle et al), and in view of the teachings of Weinschenk et al. and Hunter, Philip, one of ordinary skill in the art at the time of filing would consider it prima facie obvious to have adapted the method of Boyle et al. so as to include immunotherapy as a treatment modality for cancer because, at the time of filing, immunotherapy of cancer was well known. For example, HPV vaccines had been given to teenage girls for some years and significantly reduced the incidence of cervical cancer, and Weinschenk et al. discussed the use of tumor vaccines, adjuvant for treating cancer, human cell therapies, and cytokines [0059]. Thus, the use of a variety of immunotherapies for treating cancer was well established.
Secondly, while Boyle et al. does not specifically teach treatment with an immunotherapy when the level of inflammatory cytokine production is at or above a reference level or that an increase in the inflammatory cytokine is indicative of immune proficiency, one of ordinary skill in the art at the time of filing would have expected that an increase compared to a reference level would naturally occur when exposing the samples to “immune agonists” as Boyle et al. teach measuring the “elevation” of the inflammatory cytokines and that the magnitude of the cell-mediated immune response detected in the assay can be correlated to the disease state, progression and/or severity. Thus, one practicing the method of Boyle et al. would more than likely observe an increase and relate that increase as indicative of immune proficiency to respond to a cancer immunotherapy. Further, Boyle et al., teaches [0195] treatment of a subject having cancer comprising contacting a sample from a cancer patient with an antigen and a limiting amount of TLR agonist and measuring the presence or elevation in the level of an immune effector molecule wherein the presence or level of the immune effector molecule is indicative of the level of cell-mediated responsiveness of the subject which is indicative of the presence, absence, level or state of the condition or disorder and then treating the condition or disorder.
Thus, the aforementioned claims are viewed as obvious, when the combination of the teachings of the references are considered together.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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