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 .
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 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.
DETAILED ACTION
Claims 1-16 are pending in the instant application.
Priority
This application is a CIP of PCT/IL2022/050662, filed on 6/20/2022 which claims priority to the provisional application 63/212678 filed on 6/20/2021.
Information Disclosure Statement
The information disclosure statement (IDS) dated 11/29/2024 complies with the provisions of 27 CFR 1.97, 1.98, and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits.
Claim Interpretation
Claim 1 refers to a “TNFα related disease” this was interpreted according to the definition provided below:
“As used herein, the term "TNFα related disease" refers to any disease, condition, disorder, pathology, or any combination thereof, wherein TNFα is involved, induces, initiates, propagates, determines, or any combination or equivalent thereof, in the pathogenesis, pathophysiology, or both” (instant spec pg 10, para 070).
For the purpose of applying art to claims 2-5, Examiner selected the applicant’s open definition wherein “types of TNFα inhibitors” are discrete chemical compounds and not categories within this group of molecules (e.g. small molecule TNFα inhibitors vs. anti-TNFα antibodies):
In some embodiments, the plurality of types of TNFα inhibitors comprises or is selected from: Infliximab, Adalimumab, Golimumab, Certolizumab pegol, Etanercept, or any combination thereof.” (instant spec, pg 9, para 062).
See corresponding 112(b) rejection.
Objections to the Claims
Claim 9 contains an unnecessary word. Please replace “related disease being selected” with “related disease selected”.
Claim 10 contains a typo. Please replace “form” with “from”.
Correction is required. See MPEP § 608.01(m).
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 1-16 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 1
Claim 1, step (a), implies that the 55% reduction in IL-17 is induced by the contacting of the TNFα inhibitor, however the language fails to make this explicit. In other words, it is unclear whether (1) the contacting step is continuous for 72 hours; (2) the contacting step is performed once and the IL-17 levels are measured after 72 hours have elapsed; (3) the 55% reduction of IL-17 is observed prior to contacting the sample/subject with the TNFα inhibitor. Furthermore, it is unclear if this determining step (a) has any bearing on the chemical identity of the TNFα inhibitor administered in step (b). Because of these multiple interpretations and lack of clarity, this claim is rendered indefinite. Dependent claims 2-16 fail to cure these deficiencies, thus are also rendered indefinite.
Claim 2
Claim 2 refers to “at least one least one TNFα inhibitor comprises a plurality of types of TNFα inhibitors” creates a limitation that is impossible to satisfy. One TNFα inhibitor to comprising a plurality of TNFα inhibitors is not meaningfully interpreted. As a result his claim is rendered indefinite. Examiner recommends the language of “wherein the sample is contacted with at least two TNFα inhibitors”. Dependent claims 3-5 fail to cure these deficiencies, thus are also rendered indefinite.
Claim 3
Claim 3 refers to the “blood sample of step (a) is independently contacted with said plurality of types of TNFα inhibitors. A meaningful interpretation of “independently contacted” with a plurality of types could not be made. It is presumed applicant intends to recite that each TNFα inhibitor was added individually, with the exclusion of others; however the method refers to a single sample being taken. Thus making it impossible to test more than one TNFα inhibitor individually to one sample. Alternatively, applicant may be suggesting that two or more TNFα inhibitors are added to the same sample and some deduction is being made regarding which has the greater effect in the mixture. Because of the substantial lack of clarity and large variation in possible interpretations, this claim is rendered indefinite. Dependent claims 4-5 fail to cure these deficiencies, thus are also rendered indefinite.
Claims 2-4
Claims 2-4 refer to “types of TNFα inhibitors” wherein applicant did not provide a closed definition for this term. The instant specification recites:
“[058] In some embodiments, at least one TNFα inhibitor comprises a plurality of types of TNFα inhibitors. In some embodiments, at least one TNFα inhibitor comprises a plurality of types of different TNFα inhibitors.
“[059] As used herein, the term "plurality" comprises any integer equal to or greater than 2. In some embodiments, a plurality of types of TNFα inhibitors comprises 2-3, 2-4, 2-5, 3-4, 3-5, or 4-5 types of TNFα inhibitors.
“[060] In some embodiments, a TNFα inhibitor is an anti-TNFα antibody or a TNFα mimicking receptor. [061] In some embodiments, a TNFα inhibitor is selected from: Infliximab, Adalimumab, Golimumab, Certolizumab pegol, Etanercept, or any combination thereof.
“[062] In some embodiments, the plurality of types of TNFα inhibitors comprises or is selected from: Infliximab, Adalimumab, Golimumab, Certolizumab pegol, Etanercept, or any combination thereof” (pg 9, para 058-062).
Given this open description, one artisan may conclude “types” refers to discrete compounds (e.g. the anti-TNFα antibodies of Etanercept vs Infliximab, while another artisan may conclude this refers to different chemical classes (e.g. anti-TNFα antibodies vs small molecule therapeutics that disrupt TNFα binding.) As a result of these multiple interpretations, these claims are rendered indefinite.
Claims 4-5
Claims 4-5 refer to determining which of at least two TNFα inhibitors produces the greatest therapeutic response and administering the more effective of the group. These claims imply that step (a) of the method of parent claim 1, is not actually used to make a determination to materially change what occurs in the administration of claim 1, step (b). In other words, claim 1 encompasses testing two TNFα inhibitors in step (a) (i.e. Etanercept and Infliximab), and administering an untested TNFα inhibitor (i.e. Golimumab) in step (b); and claims 4-5 have been added to limit the method of claim 1 to actually use the information learned in step (a) to make a determination for what is administered in step (b). Because the wording is so unclear, it cannot be determined whether the method of claim 1 is fundamentally flawed or if claims 4-5 fail to further limit the parent claim 1. As a result of this lack of clarity, these claims are rendered indefinite.
Claim 12, 14
Claims 12 and 14 are drawn to the method of claim 1 “further comprising a step” of extracting RNA or proteins before step (b). One artisan may conclude this step occurs within step (a) in order to determine the most effective TNFα treatment, whereas another artisan may conclude this step occurs after step (a) as some subsequent analysis unrelated to determining the best TNFα treatment in step (a). Because of these multiple interpretations and the unknown purpose this step achieves within the claimed method, these claims are rendered indefinite. Dependent claim 16 fails to cure these deficiencies, thus is also rendered indefinite.
Claim Rejections – 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 11 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 11
Claim 11 refers to the method of claim 1, wherein the contacting period comprising “at least 72 hours”. This is already specified in parent claim 1, step (a), thus fails to further limit the scope of parent claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
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.
Claims 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over Caproni (doi: 10.1007/s10875-008-9233-0) in view of Singh (US10086072) and Yilmaz (doi: 10.1007/s00403-012-1229-1).
Claim 1, 9, 11
Regarding claims 1, 9, and 11, Caproni teaches treating a subject with the TNFα disease, psoriasis (abstract). Caproni teaches detecting IL-17 levels in the blood of these subjects at T0 and at T1 (pg 211, col 1, para 2-4), wherein T0 represents the time before a TNFα inhibitor was administered (pg 211, col 2, para 3) and T1 represents 12 weeks after T0, wherein an anti-TNFα inhibitor (e.g. Etanercept) was administered (50 mg twice a week) (pg 211, col 1, para 2; Fig 1). Caproni teaches that a greater than 55% reduction is IL-17 levels in the group that received Etanercept (Fig 1, red arrow, figure reproduced below).
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Caproni teaches performing the same procedure to test the efficacy of another TNFα inhibitor, Acitretin (Group 2) which did not yield as effective results as Etanercept (Group 1) (Fig 1). In sum, Caproni teaches all the limitations of step (a) in determining an effective TNFα inhibitor. Because the study performed by Caproni comprises a clinical trial to evaluate the effectiveness of these drugs in treating this disease, it fails to explicitly describe what the drugs the subjects of the study took to treat their disease after the study’s conclusion. However, one of skill in the art would have found it obvious to continue administering the more effective drug (e.g. Etanercept), thus satisfying the limitations of step (b).
claim 2-5
Regarding claims 2-5, Caproni teaches testing multiple drugs to determine which is most effective, but only one of these drugs is a TNFα inhibitor (Etanercept) (abstract). Caproni also does not teach mixing TNFα inhibitors. Note: the art rejection applied here is based on Examiner’s interpretation of Applicant’s claim language. See “Claim Interpretation” section above for further details.
Singh teaches treating the TNFα associated disease (e.g. Crohn’s disease) using a TNFα inhibitor, such as an anti-TNFα drug (col 9, para 2-3). Singh teaches inflammatory markers, such as cytokines, are particularly useful in the methods of the present invention for personalized therapeutic management by selecting therapy, optimizing therapy, reducing toxicity, and/or monitoring the efficacy of therapeutic treatment with one or more therapeutic agents such as biologics (e.g., anti-TNF drugs) (col 30, para 6-8). In particular embodiments, the methods described herein utilize the determination of a disease activity profile (DAP) based upon one or more (a plurality of) inflammatory markers (e.g., alone or in combination with biomarkers from other categories) to aid or assist in predicting disease course, selecting an appropriate anti-TNF drug therapy (col 30, para 6-8). Singh teaches a method of treating a TNFα disease via determining the level of a cytokine, such as IL-17 in a sample (col 31, para 3). Singh teaches the detection can be performed using an immunoassay, such as ELISA (col 31, para 5) or via detecting the corresponding RNA expression level, such as a amplification-based assay (col 31, para 5). Singh teaches the sample is blood obtained from the subject (col 15, para 4). Singh teaches the methods of the present invention can be used to predict responsiveness to a TNFα inhibitor, especially to an anti-TNFα antibody in a subject having an autoimmune disorder ( e.g., rheumatoid arthritis, Crohn's Disease, ulcerative colitis and the like) (col 6, para 5). Singh teaches testing multiple TNFα inhibitors, such as Etanercept and Infliximab; determining which of these yields an effective response in the patient (col 10, para 1-3); and administering the most effective treatment in order to provide an optimized therapy for the subject (col 13, para 2). This satisfies the limitation of “plurality of TNFα inhibitors” as Etanercept and Infliximab are discrete chemical species.
It would have been obvious to combine the teachings of Caproni and Singh because (1) Caproni teaches monitoring IL-17 levels in the blood as an objective means of measuring disease severity and treatment effectiveness, and that the administration of the anti-TNFα inhibitor, Etanercept, is effective in treating TNFα related diseases, such as psoriasis; and (2) Singh also teaches monitoring IL-17 levels in the blood as an objective means of measuring disease severity and treatment effectiveness, and teaches testing a plurality of known TNFα inhibitors in order to determine which generates the greatest response in the patients. One of skill in the art would have had a reasonable expectation of success because both references teach monitoring IL-17 levels in order to determine treatment effectiveness, and both references teach that TNFα inhibitors that reduce IL-17 levels are synonymous with the treatments that are most effective for that patient. Singh goes a step further, by explicitly stating the purpose of testing multiple TNFα inhibitors is to optimize therapeutic outcomes for patients, which comprises administering the treatment that yields the greatest response.
Claim 6
Regarding claim 6, Singh teaches the drug may be administered intravenously (col 43, para 3).
Claim 7-8
Regarding claims 7-8, Singh teaches the TNFα inhibitor is an anti-TNFα antibody, such as Infliximab (col 5, para 4).
claim 10
Regarding claim 10, Singh teaches the cytokines (or other disease markers) can be measured in a sample of the patient’s PBMC’s (col 79-80, para 7).
claim 12, 15-16
Regarding claims 12 and 15-16, Caproni teaches using ELISA to measure IL-17 levels (pg 211, col 1, para 4).
Singh teaches the detection can be performed using an immunoassay, such as ELISA (col 31, para 5) or via detecting the corresponding RNA expression level, such as a amplification-based assay (col 31, para 5). Thus satisfying the limitations of extracting RNA prior to performing step (b).
claim 13
Regarding claim 13, Caproni does not teach measuring IL-17 using quantitative RT-PCR. (RT-qPCR).
Yilmaz teaches serum IL-17 levels and IL-17 mRNA expression is higher in those with psoriasis (abstract). Yilmaz teaches using RT-qPCR to measure IL-17 levels (pg 466, col 2, para 2; abstract).
It would have been obvious to combine the teachings of Caproni, Singh, and Yilmaz, because (1) Caproni and Singh teach monitoring IL-17 levels in the blood as an objective means of measuring disease severity and treatment effectiveness, and that the administration of the anti-TNFα inhibitor, Etanercept, is effective in treating TNFα related diseases, such as psoriasis; and (2) Yilmaz teaches RT-qPCR can be used to measure IL-17 levels in patients with psoriasis. One of skill in the art would have had a reasonable expectation of success because all of the references are drawn to monitoring the progression of a TNFα related disease via monitoring IL-17 levels and Yilmaz teaches RT-qPCR can be used to measure IL-17.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA ANN ESSEX whose telephone number is 571-272-1103. The examiner can normally be reached Mon - Fri 8:30-5:00.
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/L.A.E./
Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
Prosecution Insights