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 .
The amendments and remarks filed 12/17/25 are acknowledged. Claims 16-18, and 24 have been amended. Claims 26-30 have been canceled. Claims 1-25 and 31-33 are pending.
Claims 1-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/9/24.
Claims 16-25 and 31-33 are under examination.
Withdrawn Rejection
The rejection of claim 24 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn in light of Applicant’s amendment thereto. See paragraph 10, page 3 of the previous Office action.
New Rejection Necessitated by Applicant’s Amendment
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 16-25 and 31-33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kakkar et al. (US Patent Application Publication 2017/0029499 A1, published February 2, 2017).
The claims are drawn to a method of treating a patient who has atherosclerotic cardiovascular disease with inflammation, comprising: administering COR-001 to a patient with atherosclerotic cardiovascular disease and a CRP level greater than 2 mg/L, wherein said dose of COR-001 is administered subcutaneously at a monthly equivalent dose of 2-20 mg.
Kakkar et al. teach a method of reducing risk of mortality in a selected subject with cardiovascular disease with inflammation, the method comprising administering to the subject an IL-6 antagonist (e.g., anti-IL-6 antibody) (See paragraphs 0244, 0247-0251). Kakkar et al. teach that the patient population includes subjects having atherosclerosis and inflammation (See paragraph 0300). Kakkar et al. teach that the anti-IL-6 antibody is MEDI5117, which is also known as COR-001 (See paragraph 0231). Kakkar et al. teach that the MEDI5117 is administered at a flat dose of 25-250 mg subcutaneously once every month (See paragraph 0231). Kakkar et al. teach that the anti-IL-6 antibody is administered at a dose to reduce cardiovascular mortality (See paragraph 0017 and 0136-0140). Kakkar et al. teach that the patient has elevated levels of C-reactive protein, and the patient has pre-treatment levels of CRP greater than 2 mg/ml (See paragraph 0036). Kakkar et al. teach that the IL-6 antagonist is administered at a dose, on a schedule, and for a period sufficient to reduce the patient's CRP levels below pre-treatment levels and the IL-6 antagonist is administered at a dose, on a schedule, and for a period sufficient to reduce the patient's CRP levels by at least 50% as compared to pre-treatment levels (See paragraph 0038). Regarding claims 17-24 and 33, the claims recite limitations that would inherently flow from administering the COR-001 antibody at the claimed dose. Given that the prior art method teaches administering the claimed COR-001 antibody at the required dose, the prior art method would inherently possess the results recited in the instant claims. Kakkar et al. teach that the subject has a pre-treatment CRP level greater than 2 mg/ml (See paragraph 0037).
Kakkar et al. do not teach wherein the dose of COR-001 is 5-20 mg and wherein the dose of COR-001 is 15 mg.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the concentration of the COR-001 antibody since "it is the normal desire of scientists or artisans to improve upon what is already generally known". Kakkar et al. teach a dose range that is close to the range recited in the instant claims. In the case where the claimed ranges " do not overlap with the prior art but are merely close" a prima facie case of obviousness exists. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). Further, the art recognizes the dose as a result-effective variable that can be optimized, and thus the optimal dose of the COR-001 antibody could be determined by one of skill in the art through routine experimentation. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Although Kakkar et al. teach a dose range that does not overlap, but is close, with the claimed dose range, Applicant has not demonstrated criticality of the claimed dose, and determining the optimal concentration COR-001 would be well within the knowledge of the skilled artisan.
Applicant’s Arguments
Applicant argues that the Examiner improperly relies on Titanium Metals. Applicant argues that there is no overlap in the ranges and there is no teaching in Kakkar to provide the requisite reasonable expectation for success that a dosage lower than 25-250 mg administered subcutaneously once per month would illicit the therapeutic benefits claimed in the instant application. Moreover, the instant application deals with pharmaceutical products. Applicant argues that the Federal Circuit has consistently recognized that pharmaceutical sciences constitute an unpredictable art, where even small changes in dose, formulation, molecular structure, etc. can lead to unexpected clinical outcomes, defeating any presumption of routine optimization or reasonable expectation of success.
Applicant argues that there are no experiments using COR-001 or actual data disclosed in Kakkar teaching the usefulness of the dosage range or the motivation to change the dosage in any direction, up or down.
Applicant argues that the Examiner is engaging in the benefit of impermissible hindsight
Response to Arguments
Applicant’s arguments have been fully considered but they are not persuasive.
In response to Applicant’s argument that there is no overlap in the ranges of Kakkar, although Kakkar et al. teach a dose range that does not overlap, but is close, with the claimed dose range, Applicant has not demonstrated criticality of the claimed dose, and determining the optimal concentration COR-001 would be well within the knowledge of the skilled artisan. . "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
In response to Applicant’s argument that there are no experiments using COR-001 or actual data disclosed in Kakkar teaching the usefulness of the dosage range, when the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). Furthermore, conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")).
In response to Applicant’s argument that the Examiner relies on impermissible hindsight, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Claim Status
No claims are allowed.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SANDRA CARTER whose telephone number is (571)272-2932. The examiner can normally be reached 8:00-5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa L. Ford can be reached at (571)272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SANDRA CARTER/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674