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 1-12 are pending in the instant application.
Priority
This application claims priority to the provisional applications 63883451 filed on 9/17/2025; 63810394 filed on 5/22/2025; 63785412 filed on 4/8/2025; 63761351 filed on 2/21/2025; and 63755981 filed on 2/7/2025.
Claim Interpretation
Claims 7-9 refer to “CRP” which was interpreted as “C-Reactive Protein” according to the instant specification pg 122.
Claims 10-11 refer to “NRS” which was interpreted as “Numerical Rating Scale” of pain according to the instant specification on pg 122.
Objections to the Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pg 116, para 0429. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Correction is required. See MPEP § 608.01(b).
Objections to the Claims
Claim 8 should introduce the meaning of the acronym within the claim. Please replace “a reduced CRP value” with “a reduced CRP (C-Reactive Protein) value”.
Claims 10-11 should be clarified by adding the word “pain” after the recitation of “NRS”. Please replace “NRS score” with “NRS pain score”.
Correction is required. See MPEP § 608.01(m).
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 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Varnum (US20140039164) in view of Presti (doi: 10.1161/JAHA.121.021685).
Claim 1-5
Regarding claims 1-5, Varnum teaches an anti-IL1R1 antibody comprising the heavy chain of instant SEQ ID NO: 10 (which comprises the VH of instant SEQ ID NO: 7 and HCDRs of SEQ ID NOs 1-3), as shown below with the HCDRs underlined.
instant_10 -------------------EVQLMQSGAEVKKPGESLKISCKGSGYSFSFHWIAWVRQMP 41
Varnum_34 MGSTAILALLLAVLQGVCAEVQLMQSGAEVKKPGESLKISCKGSGYSFSFHWIAWVRQMP 60
*****************************************
instant_10 GKGLEWMGIIHPGASDTRYSPSFQGQVTISADNSNSATYLQWSSLKASDTAMYFCARQRE 101
Varnum_34 GKGLEWMGIIHPGASDTRYSPSFQGQVTISADNSNSATYLQWSSLKASDTAMYFCARQRE 120
************************************************************
instant_10 LDYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS 161
Varnum_34 LDYFDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNS 180
************************************************************
instant_10 GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCC 221
Varnum_34 GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCC 240
************************************************************
instant_10 VECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEV 281
Varnum_34 VECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEV 300
************************************************************
instant_10 HNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPR 341
Varnum_34 HNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPR 360
************************************************************
instant_10 EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSF 401
Varnum_34 EPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSF 420
************************************************************
instant_10 FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 444
Varnum_34 FLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 463
*******************************************
Varnum also teaches the light chain of instant SEQ ID NO: 11 (which comprises the VL of instant SEQ ID NO: 8 and LCDRs of SEQ ID NO: 4-6), as shown below with the LCDRs underlined.
instant_11 -------------------EIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPD 41
Varnum_40 MSPSQLIGFLLLWVPASRGEIVLTQSPDFQSVTPKEKVTITCRASQSIGSSLHWYQQKPD 60
*****************************************
instant_11 QSPKLLIKYASQSFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPLTFGGG 101
Varnum_40 QSPKLLIKYASQSFSGVPSRFSGSGSGTDFTLTINSLEAEDAAAYYCHQSSSLPLTFGGG 120
************************************************************
instant_11 TKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQE 161
Varnum_40 TKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQE 180
************************************************************
instant_11 SVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
Varnum_40 SVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 233
*****************************************************
Varnum teaches the anti-IL1R1 antibodies of the invention inhibit IL1R1 form forming a complex with IL1β and IL-1R accessory protein (IL-1RAcP), thus inhibiting inflammatory biological pathways (pg 17, para 0197). Varum teaches these antibodies are thus useful for treating inflammation of the heart such as myocardial infarction, myocardial dysfunction, coronary artery bypass grafts/cancer, or inflammatory condition resulting from trauma of the affected organ (pg 5, para 0074). Varnum teaches treating “myocarditis, including chronic autoimmune myocarditis and viral myocarditis” (pg 20, para 0232). Varnum teaches treating Varnum mentions repeat administration of the antibody is needing for recurring inflammatory conditions (pg 13, para 0160). In sum, Varnum teaches treating a recurrent, cardiac-based inflammation using the same antibody as instantly claimed.
Varnum is silent on treating pericarditis.
Presti teaches anti-IL1R inhibitors (e.g. anakinra and rilonacept) as useful in treating recurrent pericarditis (abstract). Presti teaches anakinra works by binding IL-1R, preventing the binding of inflammatory signals of circulating IL1β (pg 3, col 1, para 2).
It would have been obvious to combine the teachings of Varnum and Presti because (i) Varnum teaches and anti-IL1R1 antibody that treats cardiac inflammation via blocking IL1β binding to IL1R; and (2) Presti teaches IL1R inhibitors are effective in treating recurrent pericarditis, which also function by blocking IL1β from binding IL1R. One of skill in the art would have had a reasonable expectation of success because both references teach treating inflammation of the heart using a medicament with the same mechanism of action.
Claim 6
Regarding claim 6, Varnum teaches the antibody can be administered subcutaneously (pg 17, para 0204).
Claim 7-9
Regarding claims 7-9, Varnum is silent on testing patients for their levels of CRP following treatment.
Presti teaches that over two months, patients who received anakinra exhibited a 10% reduction in CRP levels and a 30% reduction in pericardial pain on the numerical pain scale (pg 3, col 2, para 1). Presti teaches rilonacept resulted in reductions of CRP below 0.5 mg/dL by week 2 (pg 5-6, col 2, para 2-4; Fig 4, reproduced below). Thus satisfying the limitation of achieving a CRP level ≤ 0.5 mg/dL in a week.
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It is appreciated that there is no data regarding the CRP levels upon administration of the instantly claimed anti-IL1R1 antibody, the particular effects that the antibodies of Varnum exhibit on CRP levels are considered an inherent property of those antibodies. Upon the discovery that the antibodies of Varnum exhibit a particular CRP reduction level within a particular time window does not render the invention of Varnum newly patentable upon the discovery of this property. See MPEP § 2112(I). The teachings of Presti shown here are to acknowledge that CRP levels have been measured before as a means of tracking the progression of the disease, and/or the effectiveness of a treatment given.
Claim 10-11
Regarding claims 7-9, Varnum is silent on testing patients for their levels of pain using a NRS (Numeric Rating Scale) following treatment.
Presti teaches steep reductions in cardiac pain following treatment with an IL1R inhibitor, reaching a mean score of 1.2 by week 2 (pg 5-6, col 2, para 2-4; Fig 4, shown above). Thus satisfying the limitation of achieving an NRS pain score ≤ 2 in a week. It is appreciated that there is no data regarding the NRS pain levels upon administration of the instantly claimed anti-IL1R1 antibody, the particular effects that the antibodies of Varnum exhibit on reported pain are considered an inherent property of those antibodies. Upon the discovery that the antibodies of Varnum exhibit a particular pain reduction level within a particular time window does not render the invention of Varnum newly patentable upon the discovery of this property. See MPEP § 2112(I). The teachings of Presti shown here are to acknowledge that NRS pain levels have been measured before as a means of tracking the progression of the disease, and/or the effectiveness of a treatment given.
Claim 12
Regarding claim 12, Varnum is silent on the pericarditis being idiopathic.
Presti teaches that 90% of recurrent pericarditis cases are considered “idiopathic” (pg 1, col 2, para 2). Presti teaches that auto-inflammatory pathways, such as the interleukin-1 (IL-1), are critical in the disease process (pg 1, col 2, para 2).
Given the teachings of Presti that the IL1 pathway is the most critical in treating recurrent pericarditis, and that vast majority of pericarditis cases are idiopathic, one of skill in the art would have had a reasonable expectation of success of treating idiopathic pericarditis using an IL1R pathway inhibitor such as the antibodies of Varnum.
While the structures of the inhibitors of Presti vary significantly from those of Varnum, absent the evidence of unpredictability in selecting a given IL1R inhibitor, the combination of references renders the instantly claimed method of treating recurrent pericarditis using yet another IL1R inhibitor with known anti-inflammatory properties, obvious.
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
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