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 .
Claims 3, 6-12, 14, 21-22, 25-32, 35, and 39-40 are cancelled.
Claims 1-2, 4-5,13, 15-20, 23-24, 33-34, and 36-38 are pending and under examination on the merits.
Priority
This application is a 371 of PCT/JP2021/032852, filed 09/07/2021, which claims benefit of priority to JAPAN 2020-150620, filed 09/08/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Applicant cannot rely upon the certified copy of the foreign priority application to overcome any prior art rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Information Disclosure Statement
The IDS submissions filed on 03/07/2023 and 11/01/2024 have been considered by the Examiner.
Withdrawn Objections/Rejections
The objections to the drawings are withdrawn as addressed by the replacement drawings dated 03/06/2026. The rejections under 35 USC §112(b) are withdrawn in part due to corrective claim amendments dated 03/06/2026 and maintained in part (as can be seen below). The rejection of the method claims, claims 1-2, 4-5,13, 15-20, 23-24, under 25 USC §101 are withdrawn in light of the integrating claim amendments dated 03/06/2026. The rejections of claims 1 2, 4-5, 10, 13, 15-20, 23-24, 33-34, and 36-39 (regarding ambiguity as to whether the taking of a measurement and determinations occur before or after initiation of the cancer therapy) and claim 24 (regarding the drafting which required the measurement/determination to occur after initiation of cancer therapy and the ambiguity of the previously recited indication) under 35 USC §112(b) are withdrawn to corrective claim amendments dated 03/06/2026. The rejections of claims 2 and 34 under 35 USC §112(d) are withdrawn to corrective claim amendments dated 03/06/2026.
Maintained-Claim Interpretation
Applicant has limited the recitation of “cancer” to refer only to malignant tumors which are solid or hematopoietic (see paragraph 0020 of the instant specification).
Applicant has defined "cancer immunotherapy" as referring to a method of treating cancer using a biological defense mechanism such as the immune mechanism of an organism (see paragraph 0021 of the instant specification).
Applicant provides that, as used herein, the term "relative amount" with regard to cells can be interchangeably used with "ratio". Typically, the terms "relative amount" and "ratio" refer to the number of cells constituting a given cell subpopulation (e.g., CCR4- CCR6+ cell subpopulation) with respect to the number of cells constituting a specific cell population (e.g., CD4+ T cell population) (see paragraph 0026 of the instant specification). In the absence of a closed and/or clear definition of a ‘relative amount,’ any amount/measurement thereof is deemed to be within the scope of the claims.
The specification fails to provide a clear and closed definition of the “non-responder”/“non-responder group” (noting that reference to cited patent literature 1 similarly fails to provide a definition for this group). The specification provides that “[a]s used herein, "non-responder group" refers to a group of subjects determined as progressive disease (PD) in the early stage by about 9 weeks after starting therapy when the therapeutic effect from undergoing cancer therapy is determined in accordance with RECIST ver 1.1. A non-responder group is also referred to as a PD group, progressive group, or NR (Non-responder), which are interchangeably used herein” (see paragraphs 0029-0030 of the specification). It is noted that the specification teaches that the non-responder group is scored according to RECIST v1.1 criteria around 9 weeks after initiating treatment. The RECIST criteria teach that means for assessing tumor burden to classify a subject as having PD (being a non-responder) or having stable disease (presumed to be a responder; Eisenhauer et al (European Journal of Cancer, 45 (2009) 228 – 247; doi: 10.1016/j.ejca.2008.10.026).
Applicant defines the term “about” to mean a range of +/- 10% of the enumerated, modified value (see paragraph 0018 of the instant specification).
6. Applicant defines the term “threshold value” as a value that is set for a variable, which gives some type of a meaning when the variable is greater than or less than the threshold value. A threshold value is also referred to as a cut-off value herein (see for example, paragraph 0036 of the instant specification). Note that this is not a clear and/or closed definition.
7. Applicant defines the terms “reference” or “reference value” as the amount that is the baseline of comparison for determining the increase/decrease in the amount of a marker
described herein. When determining the increase/decrease of a certain amount after a certain treatment (e.g., cancer immunotherapy) relative to before the certain treatment, "reference value" can be, for example, said amount before treatment. A reference or reference value can be in a form of a given amount or relative amount of cells that is known to indicate a certain quantity (e.g., progression free survival) (see for example, paragraph 0035 of the specification). Where the claims require comparison of a relative amount to a reference value for predicting a response to therapy, it is logically implied that the relative amount is measured prior to administration of the therapy to which a response of a subject is to be predicted. It is presumed that the reference value to which the relative amount is compared for prediction is somehow further distinguished/differentiated from the relative amount for a meaningful comparison. However, that further distinction is not clearly disclosed. Therefore, any reference/baseline/control value and/or comparison of the prior art is deemed to make obvious the limitation of comparing the comparing a relative amount to a reference value.
New-Claim Interpretation
Claim 33 and its dependent claims are clearly intended to be directed towards products (a kit), but also appear to recite method steps. Because the claims are being interpreted as product claims, the method steps are not deemed to lend patentable weight and all that must be found to meet the claim is the recited structures/reagents. Therefore, a method step of administering/applying a treatment is not deemed to integrate the claims under 35 USC §101.
As recited, an "antitumor immune response" refers to any immune response against tumor in an organism (see for example, paragraph 0022 at page 13 of the specification).
Maintained-35 U.S.C. 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 33-34 and 36-38 are rejected under 35 U.S.C. 101, because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claims are directed to a judicial exception (a natural phenomenon, specifically the relationship between the relative amount (ratio relative to total CD4+ T cells) of CCR4-CCR6+CD4+ T cells and a subject’s likelihood to respond to cancer therapy and/or long-term survival). Furthermore the claims do not integrate said judicial exception in to practical application, and the claims do not recite additional elements that amount to significantly more than said judicial exception.
Where a claim describes a judicial exception, such a claim “requires closer scrutiny for eligibility because of the risk that it will ‘tie-up’ the excepted subject matter and pre-empt others from using [the judicial exception]" (federal register, p.74622, C1). While all inventions to some degree involve natural laws, products, and other judicial exceptions, the new guidance regarding patent eligibility makes clear that a practical application of these exceptions is necessary, offering “significantly more” than the exception itself. Limitations that were found not to be enough to qualify as “significantly more” include:
Mere instructions to implement an abstract idea on a computer;
Adding generic instructions that the judicial exception should be used ("apply it");
Simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality;
Adding insignificant extra solution activity to the exception ("mere data gathering"); and
Generally linking the use of the exception to a particular technological environment or field of use.
The MPEP (see § 2103-2106.07) provides a means of determining whether a particular claim is patent eligible under 35 U.S.C. 101. The Guidance requires an analysis of multiple steps, Steps 1, 2A, and 2B:
Step 1 - Following a determination of the broadest reasonable interpretation of a claim, is the claim drawn to a process, machine, manufacture, or composition of matter? If the answer to this inquiry is “Yes,” the analysis moves on to step 2A.
Step 2A - A two-prong analysis. For prong one, does the claim recite an abstract idea, law of nature, or natural phenomenon? If “Yes,” the analysis proceeds to prong two, which asks whether the claim recites additional elements that integrate the judicial exception into a practical application. If “No,” the analysis moves on to step 2B.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? If “No,” the claim is not eligible subject matter under 35 U.S.C. 101.
In the instant case, the claims are drawn to a process, so the answer to Step 1 is “Yes.”
With respect to prong one of Step 2A, the answer is “Yes,” because as indicated above, the claims are drawn to a natural phenomenon (correlation) and mental steps.
The Examiner will provide exemplary analyses of independent claim 33.
Regarding claim 33, the claim language reciting the judicial exception is, “…for predicting a response of a subject to cancer therapy, comprising a CD4 detecting agent, a CCR4 detecting agent, and a CCR6 detecting agent, wherein the prediction is performed by using a relative amount of a CCR4-CCR6+ cell subpopulation in a CD4+ T cell population of the subject as an indicator for predicting the response to cancer therapy of the subject to cancer therapy based on a relative amount of a CCR4- CCR6+ cell subpopulation in a CD4+ T cell population of the subject.”
Step 1 - Following a determination of the broadest reasonable interpretation of a claim, is the claim drawn to a process, machine, manufacture, or composition of matter? If the answer to this inquiry is “Yes,” the analysis moves on to step 2A. Here, the instant claim 33 recites, “[a] kit for….” Therefore, the instant claim 33 is directed towards a product, which is a composition of matter 35 U.S.C. 101. So the answer to step 1 is “YES.” Thus, the analysis proceeds to Step 2A.
Step 2A - A two-prong analysis. For prong 1, does the claim recite an abstract idea, law of nature, or natural phenomenon? If “Yes,” the analysis proceeds to prong 2, which asks whether the claim recites additional elements that integrate the judicial exception into a practical application. If “No,” the analysis moves on to step 2B. Here, the instant claim 33 recites a kit for predicating a response to cancer therapy based upon a measured amount of CCR4-CCR6+CD4+ T cells, which is a judicial exception. Therefore, the answer to prong 1 of step 2A is “YES.” Thus, the analysis proceeds to prong 2 of step 2A. Here, the instant claim 33 fails to recite any claim limitations which would integrate the recited judicial exception, for example, by applying or using said judicial exception to affect a particular treatment or prophylaxis for a disease or medical condition. Therefore the answer to prong two of the Step 2A analysis is “No” and the analysis progresses to step 2B.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? If “No,” the claim is not eligible subject matter under 35 U.S.C. 101. Here, the instant claim 33 pertains to a kit for predicting a response, as discussed above. Claim 33 fails to recite active steps or sufficient structure(s) that would add significantly more than the judicial exception.
Therefore, the answer to prong 2B is “No” and the instant claim 33 is therefore directed toward patent ineligible subject matter under 35 U.S.C. 101 and is therefore rejected under 35 U.S.C. 101.
Claims 36-38 do not add active steps/structures which integrate the natural phenomenon to a practical application (such as by adding an active treatment step) or which add significantly more beyond the recited judicial exception and are therefore rejected for incorporation of the judicial exception of claim 33.
Therefore, claims 33-34 and 36-38 are rejected under 35 USC §101 as directed towards patent ineligible natural phenomena and mental steps, failing to integrate or add substantially more so as to transform the claim metes and bounds into subject matter eligible for patentability.
Claim Rejections - 35 USC § 112(a)
Maintained-35 USC § 112(a)
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.
Claims 1-2, 4-5, 10, 13, 15-20, 23-24, 33-34, and 36-39 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 a method for predicting a response to a checkpoint inhibitor therapy (administration of an anti-PD-1 antibody, anti-PD-L1 antibody, or anti-CTLA4 antibody) and/or predicting long-term survival in a subject with non-small cell lung cancer (NSCLC), primary liver cancer, melanoma, and/or esophageal cancer, does not reasonably provide enablement for a method for predicting a subject’s response to any other cancer therapy for any other cancer or predicting long-term survival for a patient with any other cancer, by any comparison of the cell subpopulations.
MPEP 2164.01(a) states that in order to determine compliance with the enablement requirement, the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or is “undue.”
These factors include but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims
The instant claims are incredibly broad and encompass predicting a response to a cancer therapy and/or long-term survival of a subject, who is not required to have cancer nor a particular type of cancer, in cancer immunotherapy, which is defined at paragraph 0021 as “a method of treating cancer using a biological defense mechanism such as the immune mechanism of organisms.” Thus, the limitation of cancer immunotherapy is extensive and encompasses immune checkpoint inhibitors, engineered immune cells, oncolytic viral therapy, any gene therapy involving CRISPR for the treatment of cancer, antibody-based therapies regardless of the molecular target, cytokines, and any modulator of Toll-like receptor (TLR) or inflammasome signaling. The claims further include administration of a cancer therapeutic based upon the prediction of response/ long-term survival without limitation as to which cancers would work in the method as claimed.
The nature of the invention
The claims are broadly directed to a method for predicting an anti-tumor immune response to cancer therapy and/or long-term survival and administering a cancer therapeutic based on that prediction (where the subject is predicted to respond/not be a non-responder). The claims are directed to biological subject matter which is understood to be complex and often unpredictable.
The state of the prior art
Figure 1 of Naran et al (Frontiers in Microbiology. 9: 3158; Published: Dec 21, 2018), shown below, illustrates what one of ordinary skill in the art would have understood cancer immunotherapy to encompass, and Applicant’s definition is even broader than the treatments in this figure, encompassing mechanisms not depicted.
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One of ordinary skill in the art would understand that the treatment of cancers originating from various organ systems are associated with varying life expectancy, even when treated with the standard of care for each cancer type (see Brenner et al (The Lancet. 360 (9340): 1131-1135; Published: Oct 12, 2002)). Further, one of ordinary skill would understand that different cancer types would respond differently to immunotherapy, such as immune checkpoint inhibitors (see Bonaventura et al (Frontiers in Immunology. 10: 168; Published: Feb 8, 2019)). While conventionally long-term survival would be assessed by a 5-year overall survival metric, the instant disclosure defines a long-term responder, which is understood to be an individual who has achieved long-term survival, as a subject with progression-free survival (PFS) of 150 days or longer, with an even shorter period used for elderly subjects (see paragraph 0039 of the instant specification; see also Table 2 of Gyawali et al (JAMA Network Open. 1(2): e180416; Published: June 22, 2018); see also see Brenner et al (The Lancet. 360 (9340): 1131-1135; Published: Oct 12, 2002)). Gyawali et al demonstrate that when considering treatment with PD-1 inhibitors, as opposed to immunotherapy broadly, there is a great deal of variability in progression-free survival (PFS) response with first-line non-small cell lung cancer (NSCLC) having the most favorable response and recurrent head and neck carcinoma having the worst. Even within the same setting, first-line NSCLC for example, the PFS in response to therapy with a PD-1 inhibitor, nivolumab or pembrolizumab, can vary greatly (see Gyawali et al (JAMA Network Open. 1(2): e180416; Published: June 22, 2018)). Furthermore, Ferris et al (New England Journal of Medicine. 375 (19): 1856-1867; Published: Nov 10, 2016) teaches that among 240 patients with recurrent squamous-cell carcinoma of the head and neck treated with nivolumab, not a single patient reached PFS of 18 months or 540 days, which is greater than 500 days. Thus, the response or long-term survival of each type of cancer to immunotherapy is highly variable and unpredictable. Moreover, BDH (CN115728486A) teaches that the relative number of CCR4-CCR6+CD4+ T cells (Th17.1 cells) is not a universal, reliable predictor of long term survival across cancers, or even across solid tumor cancers (see BDH teaching that the Th17.1 cell infiltrates are associated with poor prognosis in colorectal cancer, but that the Th17.1 cell infiltrates are associated with better prognosis in esophageal cancer (see for example, page 2/12).
Additionally, the claims broadly encompass any comparison to predict long term survival. For example, no claim requires a particular ratio (relative amount) of comparison from baseline which is indicative of long-term survival or positive response to cancer treatment. The claims encompass predicting long-term survival for any cancer immunotherapy. The state of the art is such that challenges remain in predicting long-term survival given the heterogeneity in patterns and distinct mechanisms of action of different immune checkpoint inhibitors (see Jenkins et al (British Journal of Cancer. 118: 9-16; Published: Jan 2, 2018)).
Additionally, the claims recite that prediction is based upon the determination of the relative amount of the genus of CCR4-CCR6+CD4+ T cells. The instant disclosure only discloses 2 species of cells which are CCR4-CCR6+ and CD4+ : Th1/17 (Th17.1) cells and CCR6 SP cells, where it is noted that the dependent claims which require that the cell subpopulation is CXCR3+ would preclude the CCR6 SP cells, leaving only the single species of Th1/17 cells as disclosed for use in the claimed method which are CCR4-CCR6+CD4+and CXCR3+ (see for example paragraphs 0042 and 0104 at pages 19 and 41-42 of the specification, respectively). A search of the prior art fails to provide description for the genus of CCR4-CCR6+CD4+CXCR3+ cells, as recited, because only Th1/17 (also called Th17.1 cells) are disclosed as meeting the recited biomarker expression limitations (see for example, Lintermans et al ("Decreased CXCR3+CCR4-CCR6+CD4+Effector Memory T Cells in Patients with Granulomatosis with Polyangiitis", ARTHRITIS & RHEUMATOLOGY; 2014 ACR/ARHP ANNUAL MEETING; NOVEMBER 14-19, 2014; BOSTON, MA, JOHN WILEY & SONS, INC, US, vol. 66, no. S10, 1 October 2014 (2014-10-01), pages S1195-S1196, XP009535548) at the methods portion of the abstract). Therefore, Applicant, failing to demonstrate a representative number of species or a conserved primary structure, is not deemed to have been in possession of the genus of cells/subpopulations encompassed by the claims. The genus recited is deemed to encompass cells which have not yet been discovered to have this expression pattern and which have not possibly been validated to function in the method (are not enabled).
The level of one of ordinary skill
As the claims are directed to prediction of response/long-term survival and use of the prediction to inform downstream administration of a cancer therapeutic(s), the artisan is presumed to be highly skilled, tending to have an advanced degree (such as a Ph.D. or an M.D.).
The level of predictability in the art
As discussed above at point (C), the state of the art support a high degree of unpredictability in treating cancer, predicting responses to cancer treatment, and/or predicting long-term survival of a subject, even if/where the cancer therapeutic is narrowed to a checkpoint inhibitor. Based on the unpredictability of the art and the breadth of the claims, the instant specification must provide a sufficient and enabling disclosure commensurate in scope with the instant claims.
(F) The amount of direction provided by the inventor
The instant specification discloses determining the relative amount of CCR4-CCCR6+ CD4+ T cells in NSCLC patients prior to therapy with anti-PD-1 antibody and comparing the relative amount to a threshold value/baseline comparator. However, the present claims encompass methods of prediction that do not meaningfully limit the starting population, the immunotherapy, baseline/threshold value, or ratio. Additionally, the results with NSCLC patients treated with anti-PD-1 are not commensurate in scope with the instant claims which encompass prediction of long-term survival in any subject, based on any comparison, and in any immunotherapy.
The existence of working examples
Examples are provided at pages 55-71, all of which appear to have been conducted in NSCLC.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
The case is directed to biological subject matter, which is by nature complex. There examples provided pertain only to NSCLC and the state of the art fails to step in to provide enablement where the instant disclosure is lacking. The artisan would be forced into burdensome experimentation so as to effectively invent what applicant only suggests may be possible.
Thus, in light of the contradictory findings in the prior art, discovery of a correlation alone is not enabling for a method of predicting response to cancer therapy and/or long-term survival and the administering a cancer treatment based on the prediction where the prediction applies for any cancer and the treatment is broadly defined and can be for any cancer. Only a method (and kit therefore) of predicting a response to a checkpoint inhibitor therapy (administration of an anti-PD-1 antibody, anti-PD-L1 antibody, or anti-CTLA4 antibody) and/or predicting long-term survival in a subject with NSCLC, primary liver cancer, and/or esophageal cancer is deemed enabled.
Maintained-Claim Rejections - 35 USC § 112(b)
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 2, 4, 20, 24, 34, and 36 stand rejected and claims 1, 5, 13, 15-19, 23, 34, and 36 are newly 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.
Claims 2, 24, and 34, recite the comparative use of a reference value. The definition of said reference value provided in the specification is open and ambiguous. Artisans are left to dispute what reference value(s) and comparisons are encompassed by and would infringe the claims, which are therefore indefinite.
Claims 4, 20, and 36 recite the use of a non-responder threshold value, which is not defined explicitly or implicitly so as to clearly convey what value is claimed to one skilled in the art. Artisans are left to scour the disclosure and the prior art to attempt to determine what value is intended to be claimed. This ambiguity invites conflicting interpretations as to what is encompassed by the metes and bounds of the claims, which are therefore indefinite.
Claim 1 recites the limitation of “applying the cancer therapy to the subject predicted to be not a part of a non-responder group” but does not provide any steps for which this prediction is to be made. This prediction is not clearly linked by claim language to any prediction of an antitumor immune response and/or long-term survival (which is understood be made based upon a relative amount of CCR4-CCR6+ CD4+ T cells, where an increased number (noting that the reference is unspecified, see the maintained rejections under 35 USC 112(b) above). Artisans are left to determine whether the prediction of being not part of a non-responder group is the same as the prediction of an antitumor immune response to a cancer therapy, or if this reflects some new and different prediction. Therefore, the metes and bounds of claim 1 and its dependent claims (claims 2, 4-5, 13, 15-20, and 23-24), via dependency, incorporate without remedy this ambiguity and are therefore rejected as indefinite as drafted.
Claims 4 and 20 recite the limitation "the non-responder group threshold value" in line 2 and lines 1-2, respectively. There is insufficient antecedent basis for this limitation in the claim.
basis for this limitation in the claim.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 33-34, and 36-38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lomax et al (https://doi.org/10.1111/1756-185X.13076; citation 4 under Non-Patent Literature Documents on the 11/01/2024 IDS).
Regarding claims 33 and 37-38, Lomax et al teach a protocol for measuring the Th17.1 cells (CCR4-CCR6+ CD4+ T cells) and the antibodies associated therewith, including an antibody against CXCR3 (see for example, page 1278-1279). While the combined references do not specifically use the language “kit” as recited at the claim preamble, in the instant case, it is noted the terminology “kit” is not found to further limit the scope of the claims beyond requiring the inclusion of the reagents for measuring a relative amount of CCR4-, CCR6+, CD4+ T cells in a population of CD4+ T cells, as it does not clearly invoke any additional ingredients or provide the antecedent basis for terms appearing in the body of the claim (such as specific packaging or container elements, for example). See MPEP 2111.02. Consequently, when the claims are given their broadest reasonable interpretation, because the cited combination of references teach the same structural components that applicant refers to as a kit, the teachings of the cited prior art references, in combination, address the claimed elements/limitations even though the references do not employ the word “kit” in describing their invention, as the references teach all of the necessary reagents of the claimed “kit”.
With respect to the recitation “for predicting an antitumor response of a subject to cancer therapy and/or predicting long-term survival of the subject,” Applicant is reminded that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets and makes obvious the claim. Applicant is also reminded that claim scope is not limited by claim language that does not limit a claim to a particular structure (such as the active steps of how the prediction is made, applying the cancer therapy (noting no such therapy is part of the kit does not clearly require a cancer therapy, such as an anti-PD-1 antibody, as presently drafted). See MPEP 2111.04. In this case, no clear structural differences are invoked by the recitation of the intended use as claimed. Because there is no distinction between the claimed structure(s) and that of the cited prior art, it is the case that reagent(s) for measuring the cell population of Lomax et al (CCR4-CCR6+CD4+ T cells) would be capable of identifying that same cell population among a sample of CD4+ T cells, as claimed. The limitation of this intended use clause (quoted herein) fails to clearly require any additional reagent or component be provided as part of the kit (for example, the instrument is not claimed as part of the kit), and fails to impart any particular structural feature or limitation. The artisan would have compiled the ‘kit’ as recited in order to perform the method of the combined prior art references, as discussed above. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Regarding claim 34, as discussed above, the cited reference make obvious the kit of claim 33. With respect to the recited use of predicting long term survival of the subject by comparison, Applicant is reminded that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Applicant is also reminded that claim scope is not limited by claim language that does not limit a claim to a particular structure. See MPEP 2111.04. Here, no particular structure is claimed, there is no indication the prior art reagents would be incapable of performing in the kit as claimed, and there is no apparent difference between what is taught by the prior art and what is claimed.
Regarding claim 36, as discussed above, the cited reference make obvious the kit of claim 33. With respect to the recitation that comparison of the relative amount with a non-responder group threshold value is used as an indicator for predicting whether the subject is a part of a non-responder group to the cancer therapy, Applicant is reminded that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Applicant is also reminded that claim scope is not limited by claim language that does not limit a claim to a particular structure. See MPEP 2111.04. Here, no particular structure is claimed, there is no indication the prior art reagents would be incapable of performing in the kit as claimed, and there is no apparent difference between what is taught by the prior art and what is claimed.
Applicant’s Arguments and Responses:
A. Applicant argues for withdrawal of the rejections under 35 USC §101 in light of the recited step of administering a treatment, alleged to integrate the claim(s) (see page 8 of the 03/06/2026 remarks).
Response: A kit cannot comprise an active step of treatment. The recited step of applying/administering a cancer therapeutic is therefore not deemed to integrate claim 323 and its dependents. Moreover, it is noted that the claimed kit does not even comprise a therapeutic. The rejections of claims 33-34 and 36-38 are therefore maintained.
B. Applicant argues for withdrawal of the rejections under 35 USC §112(a) for lack of enablement (i) alleging the amendments narrow the claim scope, (ii) pointing to examples 4-5 and alleging that even if all of their data pertains to NSCLC, the artisan allegedly would have understood all cancers to have been enabled for use in the claimed method(s) by this data, and (iii) contesting the Examiner’s assertion that only 1 subpopulation is show as meeting the claim requirements and being CXCR3+ (see page 9-11 of the 03/06/2026 remarks).
Response: First, the question of enablement is different that the question posed by 103. The concern is whether the instant specification, in light of the state of the prior art, would have led to a reasonable expectation that the claimed method would function as claimed across the entirety of the claimed scope. Here, the answer is no. The art support that cancer treatment and long-term survival prediction are highly unpredictable and that cancer is highly heterogenous. There is no reasonable expectation that the method(s) claimed would function as claimed across all cancers and across all of the claimed cancer therapeutics (noting the expansive definitions provided by Applicant for the different therapies, such as an immunotherapy). Applicant’s amendments do not narrow the scope and Applicant’s arguments do not address the breadth of therapeutics claimed under Applicant’s own definitions. Second, examples 4-5 have been considered, but, again, only pertain to NSCLC and do not provide enablement for the method(s) for other cancers. Third, Applicant disputes that they only describe 1 subpopulation that is CCR4-CCR6+CD4+CXCR3+ (Th1/17) and 1 which is CCR4-CCR6+CD4+CXCR3- (CCR6SP). Applicant, failing to demonstrate a representative number of species or a conserved primary structure, is not deemed to have been in possession of the genus of cells/subpopulations encompassed by the claims. The genus recited is deemed to encompass cells which have not yet been discovered to have this expression pattern and which have not possibly been validated to function in the method (are not enabled). Referring to these cells as (for example, CCR4-CCR6+CD4+CXCR3+ (Th1/17), is recommended to bring the claim scope into alignment with what is enabled in the method).
C. Applicant argues for withdrawal of the rejections under 35 USC 112(b) alleging that the specification at paragraphs 100, 101, and 0102 sufficiently define the terms reference/reference value and non-responder group threshold value.
Response: The Examiner has considered these cited paragraphs and but concludes that they do no more than to ask the artisan to discover and/or dispute what reference/reference value and non-responder group threshold value would function in the claim(s) and/or be encompassed by the claim(s), so as to infringe. Because the terms remain unclarified as recited, the rejections are maintained.
Conclusion
No claim is allowed.
Notice:
Eisenhauer et al teach the RECIST v1.1 means for measurement and tumor evaluation and broadly provide means for classifying subjects as progressive disease/non-responder or stable disease/responder (see for example, pages 231-233 of Eisenhauer et al). However, there is nothing in the prior art that would reasonably teach or suggest the use RECIST version 1.1 to identify a non-responder group, detecting the relative amount of CCR4-CCR6+CD4+ T cells in that group prior to treatment, comparing that relative amount to a further relative amount detected in a test subject, and from that comparison, predicating whether or not the test subject is likely to be part of a non-responder group.
Claims 1-2, 4-5,13, 15-20, 23-24 are deemed to be free from the prior art. The closest prior art is Lomax et al. Lomax et al teach measurement of Th1/17 cells prior to administration of a checkpoint inhibitor as predictive of developing sarcoidosis in melanoma patients. However, Lomax et al, even when viewed in light of the state of the art, does not reasonably suggest prediction of an anti-tumor response in response to a cancer therapy or long-term survival based upon the specific population of cells that are CD4+, CCR4-, and CCR6+ with a reasonable expectation of success (see MPEP §2143(I)(A)(example 7) and §2144.08(I)(A)(4)(e), citing In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988)).
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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