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 .
Status of the Claims
It is acknowledged that in the response filed July 2, 2026, Applicant amended claims 1 and 10-14 and cancelled claims 2, 3, and 18-20.
Claims 1 and 4-17 are currently pending.
Claim 4 was previously withdrawn as being drawn to nonelected subject matter in the office action mailed April 6, 2026.
Claims 1 and 5-17 are herein examined to the extent that they read on the species elected without traverse in the response filed February 23, 2026.
Summary of Response to Applicant’s Arguments
This action is in response to the papers filed July 2, 2026. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be persuasive. Detailed responses are documented on pages 4-5, 7, 13, 15-16, and 18-19 of this office action. Any new grounds of rejection presented in this Office Action are necessitated by Applicant’s amendments. Any rejections or objections not reiterated herein have been withdrawn. This action is made FINAL.
As claims 2, 3, 19 were cancelled, the rejections of those claims under 35 U.S.C. 112(a) and 112(d) have been withdrawn. Modified rejections to the amended claims under 35 U.S.C. 112(b), 35 U.S.C. 101, and 35 U.S.C. 102(a)(1)/35 U.S.C. 103 are set forth below.
Priority
It is acknowledged that the instant application is a 371 of international PCT Application No. PCT/US2022/021377, filed 3/22/22.
Applicant’s claim for the benefit of prior-filed applications under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The provisional applications filed 3/22/21 and 4/01/21 do not provide sufficient support for all limitations of the invention as claimed in the instant application. See MPEP 211.05(A).
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/163,935, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The provisional application lacks support for limitations regarding additional treatment(s). Accordingly, claims 10-15 are not entitled to the benefit of the prior application.
The disclosure of the prior-filed application, provisional Application No. 63/169,392, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The provisional application lacks support for limitations regarding additional treatment(s). Accordingly, claims 10-15 are not entitled to the benefit of the prior application.
The effective filing date for claims 1, 5-9, 16, and 17 is considered to be 3/22/21. The effective filing date for claims 10-15, and 18-20 is considered to be 3/22/22.
Response to Arguments
In the response, Applicant argued that the disclosure of “quantifying gene expression levels in patient tumors” in the provisional Application No. 63/163,935 would be understood by an ordinary artisan to include both fresh and fixed tumor samples
In response to the successful argument that claims 5 and 6 are implicitly supported by the disclosure of Application No. 63/163,935, the Priority section below has been modified. The effective filing date of claims 5 and 6 is considered to be March 22, 2021.
Applicant argued that the provisional Application No. 63/163,935 supported additional treatments because it disclosed “biomarker[s] of patient response to immune checkpoint inhibitors” and “biomarkers for predicting patient response to several different therapies.” Applicant argued that the references cited in Application No. 63/169,392, which were incorporated by reference, support the claimed species of immune checkpoint inhibitors in claims 10-15.
These arguments have been carefully considered and are not found to be persuasive. The provisional Application No. 63/163,935 discloses that biomarkers may be useful for the purposes of predicting response to different immunotherapies. It does not disclose or reasonably suggest combination therapies, as required by claims 10-15. Additionally, MPEP 608.01(p) and 37 C.F.R. 1.57 allow that material may be incorporated by reference. However, so-called “essential material” (such as material which is necessary to provide or support written description) may only be incorporated by reference by way of an incorporation by reference to a U.S. patent or U.S. patent application publication. Therefore, the disclosure of material such as specific immune-checkpoint inhibitors in the cited non-patent literature of Application No. 63/169,392 is not sufficient to provide support for claims 10-15. The effective filing date of these claims remains March 22, 2022.
Information Disclosure Statement
Information disclosure statements from 5/17/24, 11/21/24, 4/10/25, 9/02/25, and 10/21/25, and 7/06/26 have been received. IDS entry #118 from 5/17/24 has not been considered, as it is missing a year.
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.
Claims 10-15 remain/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.
This rejection of claims 10-15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, has been revised and updated in response to claim amendments filed on 07/02/2026.
Claims 10-15 are rejected for the recitation of “administering a first additional treatment” in claim 10 and “administering a second additional treatment” in claim 14 because it is unclear if the administration of the treatment is dependent on the expression level of NEAT1. Claim 1 specifies that a generic immunotherapy treatment is given specifically to subjects having samples with expression levels of NEAT1 above a reference level of NEAT1. It is not clear if claims 10 and 14 require that the additional treatment(s) are similarly restricted to only subjects having a sample having an expression level of NEAT1 above a reference. As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter. If what is meant is that the additional treatment(s) are administered “to the subject having an expression level of NEAT1 above the reference level”, the claims must be amended to reflect that meaning.
Claims 12 and 13 are rejected because they recite limitations of claim 11’s “immune checkpoint inhibitor.” This recitation is confusing because it is unclear whether the claims are requiring that the first additional treatment be an immune checkpoint inhibitor, or if they’re merely further limiting the group from which the first additional treatment is selected (i.e. “wherein the first additional treatment is selected from the group consisting of [an immune checkpoint inhibitor which is not an inhibitor of PD-1/PD-L1], a resection, a chemotherapy, and radiation”). Clarification is requested.
Response to Arguments
In the reply, Applicant argued that amended claims are clear and not indefinite.
This argument has been fully considered and is found to be partially persuasive. Amendments to the claims and cancellation of claims 2, 3, and 18-20 have overcome some of the rejections under 35 U.S.C. 112(b).
Modified rejections are set forth above to address issues of indefiniteness or lack of clarity arising from the amended claims.
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 and 5-17 remain/are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims have been evaluated using the 2019 Revised Patent Subject Matter Eligibility Guidance (see Federal Register Vol. 84, No. 4, Monday, January 7, 2019).
This rejection of claims 1 and 5-17 under 35 U.S.C. 101 has been revised and updated in response to claim amendments filed on 07/02/2026.
Step 1: The claims are directed to the statutory category of a process.
Step 2A, prong one: Evaluate Whether the Claim Recites a Judicial Exception
The instant claims recite a law of nature. The claims are directed to a correlation between the expression level of biomarkers (NEAT1 and/or HNRNPH1) and patient response to immunotherapy. This type of correlation is a consequence of natural processes, similar to the naturally occurring correlation found to be a law of nature by the Supreme Court in Mayo.
The instant claims recite abstract ideas. The claims recite a step of “comparing” the expression level of NEAT1 to a reference. Neither the specification nor the claims set forth a limiting definition for “comparing” and the claims do not set forth how this step is accomplished. The “comparing” step broadly encompasses mental processes. For example, one may “compare” the expression levels by looking at data and thinking about whether the expression level is higher than a reference level. Mental processes, which are concepts performed in the human mind (including observation, evaluation, judgement, and opinions) are considered to be abstract ideas.
The claims recite a step of “determining” that the expression level of NEAT1 is above the reference level. Neither the specification nor the claims set forth a limiting definition for “determining” and the claims do not set forth how this step is accomplished. The “determining” step broadly encompasses mental processes. For example, one may “determine” the expression level is higher than a reference level by looking at data and thinking about how the two levels compare. Mental processes, which are concepts performed in the human mind (including observation, evaluation, judgement, and opinions) are considered to be abstract ideas.
The claims recite a step of ”selecting” an immunotherapy treatment for a subject who has a level of NEAT1 above a reference level. Neither the specification nor the claims set forth criteria for selection of any particular immunotherapy and the claims do not set forth how this step is accomplished. The broadest reasonable interpretation of the “selection” step is that it may be accomplished by a mental process. For example, one may “select” the treatment by thinking about a subject’s expression level of NEAT1 and deciding which treatment to administer. Mental processes, which are concepts performed in the human mind (including observation, evaluation, judgement, and opinions) are considered to be abstract ideas.
Step 2A, prong two: Evaluate Whether the Judicial Exception Is Integrated Into a Practical Application
The claims do NOT recite additional steps or elements that integrate the recited judicial exception(s) into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or a technological field;
An additional element that applies or used a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing;
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
In addition to the judicial exceptions, the claims recite a step of “obtaining” a sample comprising a plurality of cells from a tumor of the subject. This step is not considered to integrate the judicial exceptions into a practical application because it merely adds insignificant extra-solution activity (data gathering) to the judicial exceptions.
In addition to the judicial exceptions, the claims recite a step of “determining” a tumor expression level of NEAT1 in the sample. This step is not considered to integrate the judicial exceptions into a practical application because it merely adds insignificant extra-solution activity (data gathering) to the judicial exceptions.
In addition to the judicial exceptions, the claims recite “selecting an immunotherapy treatment” and “administering the immunotherapy treatment” to a subject having a sample with an expression level of NEAT1 above a reference level. Claims 10, 14, and 20 recite step(s) of administering additional treatment(s). These administration steps are not particular. They are not specifically identified so that they do not encompass all application of the judicial exceptions, because they do not link the measured levels of NEAT1 to the phenotype identified in the specification (i.e. higher likelihood of survival after treatment with anti-PD-1 therapies in patients having higher expression of NEAT1). These steps are merely instruction to apply the exception in generic ways. Thus, the administration steps do not integrate the mental analysis step into a practical application.
Claim 11 recites that the first additional treatment is selected from a second immune checkpoint inhibitor, a resection, a chemotherapy, and radiation. Claim 12 limits the second immune checkpoint inhibitor to not an inhibitor of PD-1 or PD-L1, while Claim 13 requires that the second immune checkpoint inhibitor is selected from inhibitors of CTLA-4, Lag3, or Tim3. Claim 15 limits the second additional treatment to CAR T therapy. The administering steps are not specifically linked to the relative expression level of NEAT1. Since the administering steps do not have more than a nominal or insignificant relationship to the judicial exception, these claims do not integrate the mental analysis step into a practical application.
Step 2B: Evaluate Whether the Claim Provides and Inventive Concept
In addition to the judicial exceptions, the claims recite steps of “obtaining” a sample comprising a plurality of cells from the tumor of the subject, “determining” a tumor expression level of NEAT1 in the sample, and “administering” the immunotherapy treatment or additional treatments to the subject. These steps do not amount to significantly more because they simply append well-understood, routine, and conventional activities previously known in the art, specified at a high level of generality, to the judicial exceptions.
These steps are recited a high level of generality. Determining the expression levels of NEAT1, obtaining a sample comprising a plurality of cells from a tumor, selecting an immunotherapy treatment, and administering a treatment merely instruct a scientist to use any known technique for measuring expression levels, obtaining a tumor cell sample, and selecting and administering a therapy. The claim does not require the use of any particular non-conventional reagents or equipment or methodology. When recited at this high level of generality, there is no meaningful limitation that distinguishes this step from well-understood, routine, and conventional activities engaged in by scientists prior to applicant’s invention and at the time the application was filed.
Additionally, the teachings in the specification demonstrate the well-understood, routine, and conventional nature of additional elements because it teaches that the additional elements are well-known or commercially available. For example, the specification teaches the following:
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Further, it is noted that the courts have recognized the following laboratory techniques as well-understood, routine, and conventional activity in the life science arts when they are claimed in a merely generic manner (e.g. at a high level of generality) or as insignificant extra-solution activity.
Determining the level of a biomarker in blood by any means, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1362, 123 USPQ2d 1081, 1088 (Fed. Cir. 2017);
Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015);
Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017);
Immunizing a patient against a disease, Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1063, 100 USPQ2d 1492, 1497 (Fed. Cir. 2011);
Analyzing DNA to provide sequence information or detect allelic variants, Genetic Techs., 818 F.3d at 1377; 118 USPQ2d at 1546;
Freezing and thawing cells, Rapid Litig. Mgmt. 827 F.3d at 1051, 119 USPQ2d at 1375;
Amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014)
For the reasons set forth above the claims are not directed to patent eligible subject matter.
Response to Arguments
In the reply, Applicant argued that amended claim 1 comprises elements integrating a judicial exception (i.e. and administering step) which is not conditional and requested reconsideration and withdrawal of the rejections.
This argument has been fully considered but is not found to be persuasive. The amendment to claim 1 does restrict the selecting and administering steps to patients with samples having an expression level of NEAT1 above a reference level. However, the amended limitations do not integrate the judicial exception into a practical application because the treatment recited in claim 1 is not particular. Only anti-PD-1 therapies are specifically linked to NEAT1 expression levels in the examples disclosed in the instant application. Claim 1’s recited “immunotherapy treatment” is recited at such a high level of generality that it is at best mere instruction to apply the exception.
Modified rejection under 35 U.S.C. 101 is set forth above.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1, 7-11, 13, 16, and 17 remain/are rejected under 35 U.S.C. 102(a)(1) as anticipated by Jerby et al. (published April 11, 2019; International Publication No. WO 2019/070755).
This rejection of claims 1, 7-11, 13, 16, and 17 under 35 U.S.C. 102(a)(1) has been revised and updated in response to claim amendments filed on 07/02/2026.
Regarding claim 1, Jerby teaches a method of selecting a treatment for and treating a subject who has a tumor, the method comprising: obtaining a sample comprising a plurality of cells from the tumor of the subject (pg. 425, claim 20); determining a tumor expression level of nuclear paraspeckle assembly transcript 1 (NEAT1) in the subject (pg. 422, claim 9); comparing the tumor expression level of NEAT1 to a reference expression level of NEAT1 (par. 176); selecting an immunotherapy treatment for a subject with a particular gene expression level (pg. 425, claim 20); and administering the immunotherapy treatment to the subject (pg. 425, claim 20).
Jerby does not teach verbatim that the treatment is selected and administered to a subject who has a level of NEAT1 above the reference level. However, Jerby does teach detecting a down-regulated biomarker signature which can be composed of NEAT1 alone, referred to as ‘exclusion-down.’ Jerby teaches that the exclusion-down signature is associated with low survival or non-response to immunotherapy and that lack of detection of the signature is associated with high survival and response to immunotherapy (par. 29; claim 9). Jerby teaches administering an immunotherapy if an exclusion signature is reduced or below a reference level (par. 47-48). Due to the way that the exclusion-down signature is defined (par. 171), having an exclusion-down signature which is reduced compared to a reference level is the equivalent of having the comprised biomarker(s), including NEAT1, be above the reference level. Therefore, Jerby is considered to have met the limitations of claim 1.
Regarding claims 7-9, Jerby teaches administration of an immune checkpoint inhibitor (par. 13), where the immune checkpoint inhibitor targets PD-1 (par. 15) and is an antibody (par. 340).
Regarding claim 10, Jerby teaches administering a first additional treatment (par. 340; claim 20).
Regarding claims 11 and 13, Jerby teaches that the first additional treatment is a second immune checkpoint inhibitor which targets CTLA-4, Lag3, or Tim3 (pg. 425, claim 20, 25; par. 340). In this case, the “immunotherapy treatment” and the “first additional treatment” are any two of the inhibitors used in phased combination therapy.
Regarding claims 16 and 17, Jerby teaches that the sample is from a glioblastoma or carcinoma or melanoma (par. 307)
Response to Arguments
In the reply, Applicant argued that Jerby’s disclosure of NEAT1 is not an enabling disclosure of the claimed subject matter because it merely names or describes the subject matter as a member of large lists of genes. Applicant compared the use of Jerby with Elan Pharm., Inc. v Mayo Found. For Med. Educ & Research, where the courts found that mere disclosure of the claimed transgenic mouse was not enabled because one of ordinary sill in the art would not be able to produce it without undue experimentation.
Response to Arguments: In this case, NEAT1 is recited as part of a large set of biomarkers known as an ‘exclusion-down’ signature. However, as the instant claims do not explicitly exclude the assessment of additional biomarkers as part of the method (‘comprises’), Jerby need not isolate NEAT1 as a biomarker indicating appropriate immunotherapy treatment. Jerby allows that any one of the biomarkers encompassed by the exclusion-down signature may be used in its recited method (claim 9). Regarding whether Jerby’s disclosure is enabling, Jerby explains that the exclusion-down signature indicates that a given biomarker is downregulated in malignant cells that are associated with exclusion and/or upregulated when there is immune cell infiltration (par. 171). Jerby also demonstrates that the signature is associated with immune resistance to immune checkpoint inhibitors. For example, in Figure 55F, higher expression of biomarkers within the exclusion-down signature is significantly associated with complete response vs. partial response vs. progressive disease (CR, PR/SD, and PD, respectively) in subjects treated with anti-PD-1 therapy (par. 12, 139).
MPEP 2121(III) states that: “A prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; ‘proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation.’” Methods of determining expression levels of biomarkers are well-understood and routine (see Jerby: par. 60, 162, 187). Likewise, selecting and administering immunotherapy treatments to human subjects is routine (par. 340). In this case, it would be well within the capabilities of a person with ordinary skill in the art to make and use the invention given Jerby’s disclosure.
The rejections are maintained.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 5 and 6 remain/are rejected under 35 U.S.C. 103 as unpatentable over Jerby et al. (published April 11, 2019; International Publication No. WO 2019/070755), as applied to claim 1 above, and in view of Gao et al. (published March 13, 2020; Front Oncol. 2020 Mar 13;10:310).
This rejection of claims 5 and 6 under 35 U.S.C. 103 has been revised and updated in response to claim amendments filed on 07/02/2026.
Jerby teaches the limitations of claim 1, as discussed above.
Regarding claims 5 and 6, Jerby does not explicitly teach that the sample used in the method of treating is a fresh tumor sample or a fixed tumor sample.
Gao teaches the use of fresh and fixed tumor samples in targeted cancer therapy (Introduction).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to combine the teachings of Jerby and Gao. One would have been motivated to do so in order to better preserve DNA for analysis or make use of convenient and commonly used clinical samples (pg. 2, col. 2).
Claims 12, 14, and 15 remain/are rejected under 35 U.S.C. 103 as unpatentable over Jerby et al. (published April 11, 2019; International Publication No. WO 2019/070755), as applied to claims 1, 10, and 11 above, and in view of Shi et al (published August 29, 2019; Cancer Immunol Res. 2019 Nov;7(11):1803-1812).
This rejection of claims 12, 14, and 15 under 35 U.S.C. 103 has been revised and updated in response to claim amendments filed on 07/02/2026.
Jerby teaches the limitations of claims 1, 10, and 11, as discussed above.
Regarding claims 12, 14, and 15, Jerby does not explicitly teach administering a second immune checkpoint inhibitor which is not an inhibitor of PD-1 or an inhibitor of PD-L1.
Regarding claim 12, Shi teaches treatment of a second immune checkpoint inhibitor which is not an inhibitor of PD-1 or an inhibitor of PD-L1 (abstract). In this case, Shi teaches simultaneously administering CTLA-4 and PD-1 inhibitors to treat tumors – the second immune checkpoint inhibitor would be the inhibitor of CTLA-4.
Regarding claims 14 and 15, Shi teaches administering a second additional treatment which is CAR T therapy (abstract).
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention to combine the teachings of Jerby and Shi. One would have been motivated to do so in order to achieve durable antitumor response and improved survival (Shi: Abstract).
Response to Arguments
In the response, Applicant argued that Jerby is not applicable as prior art for the reasons discussed for rejections under 35 U.S.C. 102(a)(1). Applicant further argued that obviousness rejections require evidence of a reasonable expectation that a combination would work for its intended purpose. Applicant argued that Jerby’s disclosure of NEAT1 as part of a ‘laundry list’ of genes that are associated with immune response and the absence of working examples would not provide sufficient motivation for a person with ordinary skill in the art to choose to measure NEAT1 out of a list of genes for the purposes of selecting and administering an immunotherapy.
These arguments have been fully considered and are not found to be persuasive. As discussed for 35 U.S.C. 102(a)(1) above, the instant claims do not preclude the use of NEAT1 as part of a larger biomarker signature and Jerby’s disclosure may be considered an enabling disclosure for the purpose of prior art.
MPEP 2164.06 states “a considerable amount of experimentation is permissible, if it is merely routine.” Methods of determining expression levels of biomarkers and of selecting and administering immunotherapy treatments to human subjects are routine (see Jerby: par. 60, 162, 187, 340), and Jerby provides support for the association of NEAT1 with immunotherapy. Therefore, even if Jerby did not anticipate the limitations of the claim, a person with ordinary skill in the art would have had reasonable expectation of success trying NEAT1 as a biomarker for likelihood of response to immunotherapy.
The rejections are maintained.
Conclusion
No claims are allowed.
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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/C.M.J./Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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