DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The preliminary amendment of 9/5/23 has been entered in full. Claims 2, 4, 6-8, 11, 13, 17, 21, 51-52, 59, 67, 69, 71-72, 75, 81, 86, 98, 100 and 118-120 are amended. Claims 3, 5, 9-10, 12, 14-16, 18-20, 22-50, 53-58, 60-66, 68, 73-74, 76-80, 82-85, 87-96, 99 and 101-117 are canceled. New claims 121-126 are added.
Claims 1-2, 4, 6-8, 11, 13, 17, 21, 51-52, 59, 67, 69-72, 75, 81, 86, 97-98, 100 and 118-126 are pending.
Specification
The disclosure is objected to because of the following informalities:
---The title of the invention is not descriptive because (1) it is directed in part to a composition, which is a product, the claims are limited to methods; and (2) it is directed in part to a method of using an IL-6R antagonist, but the claims are limited to use of an antibody that binds to IL-6R. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “METHODS FOR TREATING POLYMYALGIA RHEUMATICA BY ADMINISTERING AN ANTIBODY THAT SPECIFICALLY BINDS IL-6R.
---At ¶ 214, the specification states, “American College of Rheumatology criteria for rheumatic diseases including polymyalgia rheumatica can be found at www.rheumatology.org/Practice-Quality/Clinical-Support/Criteria/ACR-Endorsed-Criteria, incorporated herein in its entirety”. However, per 37 CFR 1.57(e), “an incorporation by reference by hyperlink or other form of browser executable code is not permitted”. See also MPEP § 608.01.
Appropriate correction is required.
Claim Interpretation
The instant specification defines the term about in ¶ 208:
“As used herein, the term "about," when used in reference to a particular recited numerical value, means that the value may vary from the recited value by no more than 1%. For example, as used herein, the expression "about 100" includes 99 and 101 and all values in between (e.g., 99.1, 99.2, 99.3, 99.4, etc).”
Claims 8, 11, 17, 52, 120, 122 and 126 each employ the term “about” in conjunction with a numerical value; as such, in each case the definition set forth in the specification applies to the term as used in each claim.
Claim Objections
Claims 13, 71 and 86 are objected to because of the following informalities:
In claim 13, line 2, “disease modifying” should be “disease-modifying”. Compare with the specification at ¶ 590.
In claim 71, line 5, before the word “Short”, there is an extraneous “and”, which should be removed.
In claim 71, line 7, “activity- Visual” should be “activity-Visual”.
In claim 86, the acronym “GC” should be accompanied by the full terminology the first time it appears in the claim; e.g., “glucocorticoid (GC)”.
Appropriate correction is required.
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 13 is 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 pre-AIA the applicant regards as the invention.
Claim 13 recites the phrase “a disease modifying antirheumatic drug (cDMARD)”, which is indefinite because acronym contains the letter “c” that is not represented by the full terminology. The specification does not definite the term cDMARD, but indicates at ¶ 590 (published application) that it standards for “conventional disease-modifying antirheumatic drug”. Thus from the phrasing of claim 13 it is unclear whether it is directed more broadly to a DMARD or more narrowly to a cDMARD.
Claim 71 contains the trademark/trade name: “SF-36v2”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an outcome measure and, accordingly, the identification/description is indefinite.
Note on Prior Art Rejection(s)
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 2, 4, 6-8, 11, 13, 21, 51-52, 59, 67, 69-72, 75, 81, 86, 97-98, 100, 118 and 121-124 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the Record History for Clinical Trial NCT03600818, version 33, dated 4/14/20, 19 pages as printed from https://clinicaltrials.gov/study/NCT03600818. The earliest date to which the instant application claims priority is 4/6/22.
Claim 1 encompasses a method for treating polymyalgia rheumatica (PMR) in a subject in need thereof comprising administering an effective amount of an antibody that specifically binds IL-6 receptor. The ‘818 publication teaches treatment of “patients with polymyalgia rheumatica (PMR)” with sarilumab, an anti-IL-6 antibody (page 7). As such, the teachings of ‘818 anticipate claim 1.
Claims 2, 4, 6 and 11 encompass a method of claim 1 wherein the subject has PMR that is refractory to steroid taper (claim 2), wherein the steroid comprises prednisone (claim 4) and wherein the subject was treated with a dose of ≥7.5 mg/day of prednisone (claim 6) or wherein the dose of prednisone is tapered (claim 11). ‘818 further teaches “inclusion criteria” for the patients, which “must have had at least one episode of unequivocal PMR flare while attempting to taper prednisone at a dose that is ≥7.5 mg/day within the past 12 Weeks” (page 11). As such, the teachings of ‘818 also anticipate claims 2, 4, 6 and 11.
Claims 7 and 8 encompass a method of claim 1 wherein the antibody is administered in combination with another agent (claim 7) that is prednisone (claim 8). ‘818 further teaches that prednisone is given along with sarilumab; see Group 1 on pages 8-9. As such, the teachings of ‘818 also anticipate claims 7 and 8.
Claim 13 encompasses a method of claim 1 wherein the subject was previously treated with a disease-modifying antirheumatic drug such as methotrexate. ‘818 further teaches that the subjects are excluded if given a MTX (methotrexate) dose of over >15 mg/week within 3 months of baseline (page 12), the corollary of which is that a subjects given a lower dose are to be included; as such the teachings of ‘818 also anticipate claim 13.
Claim 21 encompasses a method of claim 1 wherein the antibody, in the alternative, is sarilumab. The teachings of ‘818 described above that anticipate claim 1 are directed to an antibody that is sarilumab. As such, the teachings of ‘818 also anticipate claim 21.
Claim 51 is an independent claim encompassing a method of reducing the dependence of a subject with MPR on a background therapy comprising corticosteroids for the treatment of PMR comprising three steps: (a) selecting a subject with PMR that is partially controlled with a background therapy comprising corticosteroids; (b) administering a defined dose of a therapeutically effective amount of an antibody that specifically binds IL-6 receptor at a defined frequency for an initial treatment period while maintaining the subject’s background PMR therapy for the initial treatment period; and (c) gradually reducing the dosage of corticosteroids administered to the subject over the course of a subsequent treatment period while continuing to administer the antibody to the subject at the defined dose used during the initial treatment period. The term “background therapy” is not defined by the instant specification, and broadly encompasses any form of continuing administration of corticosteroids. The term “defined dose” is not defined by the instant specification and is interpreted broadly as encompassing any form of dosing parameters.
With regard to step (a), ‘818 teaches “inclusion criteria” for the patients, which includes that they “Patients must be on prednisone of at least 7.5 mg/day (or equivalent) and not exceeding 20 mg/day at screening and during the screening period” and they “must have had at least one episode of unequivocal PMR flare while attempting to taper prednisone at a dose that is ≥7.5 mg/day within the past 12 Weeks prior to screening” (page 11). These teachings meet the step of selecting a subject that is partially controlled with a background therapy comprising corticosteroids. With regard to step (b), ‘818 teaches treatment of “patients with polymyalgia rheumatica (PMR)” with sarilumab, an anti-IL-6 antibody (page 7). ‘818 further teaches that the subjects are given sarilumab “once every 2 weeks” (page 8), which is a defined dose (one dose) at a defined frequency (every 2 weeks), while continuing prednisone administration (page 9). With regard to step (c), ‘818 further teaches that the corticosteroid will be tapered during the treatment with sarilumab (page 7). As such, the teachings of ‘818 meet the limitations of claim 51 and thus anticipate the claim.
Claim 52 encompasses a method of claim 51 wherein the antibody, in the alternative, is sarilumab. The teachings of ‘818 described above that anticipate claim 51 are directed to an antibody that is sarilumab. As such, the teachings of ‘818 also anticipate claim 52.
Claim 59 encompasses a method of claim 51 wherein the subject, in the alternative, is at least 50 years old. ‘818 further teaches that the minimum age for patients is “50 Years” (page 10). As such, the teachings of ‘818 also anticipate claim 59.
Claim 67 depends from claim 50 and recites a further limitation directed to one of the alternatives of claim 59, wherein the subject does not have a connective tissue disease selected from a group include systemic lupus erythematosus (SLE). Notably, claim 67 does not limit the subject to such an embodiment; thus, claim 67 encompasses each of the alternative subjects of claim 59, just with the alternative directed to the subject not having a connective tissue disease is further narrowed to not having SLE. As such, claim 67 encompasses the embodiment of claim 59 directed to the subject being at least 50 years old, and therefore is anticipated by ‘818 for the same reasons as claim 59. However, it is further noted that ‘818 excludes subjects with SLE (page 11), and thus the teachings of ‘818 also meet the limitations of claim 67 as directed to this alternative.
Clauses 69-72, 75, 81 and 86 depend from claim 51 and in each case further limit the method by means of a concluding “wherein” clause that recites results that are achieved by the claimed method. In each case, the concluding wherein clause has been fully considered in context of the parent claim(s), but does not render the claimed method patentably distinct from a method of the parent claim taught by the prior art because it simply expresses the intended result of a process step positively recited. See MPEP 2111.04, which states that a "whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited" (Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Specifically, in claims 69-72, 75, 81 and 86, the claims simply express the intended result of a process step positively recited (administering sarilumab to the subject). As such, the teachings of ‘818 that anticipate claim 51 also anticipate claims 69-72, 75, 81 and 86.
Claim 97 is an independent claim encompassing a method for treating PMR in a subject in need thereof comprising administering an effective amount of an antibody that specifically binds IL-6 receptor, wherein said antibody comprises the heavy chain CDR sequences of SEQ ID NO: 3-5 and the light chain CDR sequences of SEQ ID NO: 6-8, and wherein the subject cannot tolerate steroid taper. The CDRs sequences of SEQ ID NO: 3-5 and 6-8 are those of sarilumab. As such, the teachings of ‘818 described above for claims 1 and 2 also meet the limitations of claim 97, and thus also anticipate claim 97.
Claims 98 and 121-123 each depend from claim 97 and present further limitations that correspond to the same further limitations presented in, respectively, claims 4, 6, 11 and 21, each depending from claim 1. The teachings of ‘818 that anticipate the further limitations of claims 4, 6, 11 and 21 are described above, and these same teachings anticipate the further limitations of claims 98 and 121-123. As such, the teachings of ‘818 also anticipate claims 98 and 121-123.
Claim 100 encompasses a method of claim 100 wherein the subject is an adult. ‘818 further teaches that the minimum age for patients is “50 Years” (page 10). As such, the teachings of ‘818 also anticipate claim 100.
Claims 118 and 124 encompass a method of claim 1 (claim 118) or claim 97) (claim 124) wherein the antibody is administered subcutaneously. ‘818 further teaches that the sarilumab is administered by subcutaneous injection (page 8). As such, the teachings of ‘818 also anticipate claims 118 and 124.
Claim Rejections - 35 USC § 103
The following is a quotation of 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 of this title, 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 negatived by the manner in which the invention was made.
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 at the time any inventions covered therein were effectively filed 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 at the time a later invention was effectively filed 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.
Claims 17, 119-120 and 125-126 are rejected under 35 U.S.C. 103(a) as being unpatentable over the Record History for Clinical Trial NCT03600818, version 33, dated 4/14/20, 19 pages as printed from https://clinicaltrials.gov/study/NCT03600818, as applied to claim 1 above, and further in view of Boyapati et al, 2020/0405851, published 12/31/20 (cited on a 2/20/24 IDS). The earliest date to which the instant application claims priority is 4/6/22.
Claim 17 encompasses a method of claim 1 wherein the antibody is administered at a dose in the range of about 150 to about 200 mg. The teachings of ‘818 that anticipate parent claim 1 are set forth above. ‘818 does not further specify the dose of sarilumab to be administered.
Boyapati teaches that IL-6 is a pro-inflammatory cytokine (¶ 3) that plays a role in inflammatory, metabolic, neural and regenerative processes (¶ 4), and that sarilumab is a human antibody that binds membrane-bound and soluble IL-6 receptor-α to inhibit IL-6 signaling (¶ 5). Boyapati teaches a dose of about 150 to about 200 mg of sarilumab for treatment of rheumatoid arthritis (¶ 10).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treatment of PMR by administering sarilumab taught by ‘818 and modify it to administer the sarilumab in dose between about 150 to about 200 mg as taught by Boyapati. The person of ordinary skill in the art would have been motivated to make such a change because ‘818 teaches administering sarilumab but does not specify a particular quantity for the dose, and Boyapati provides a quantity of sarilumab to be administered that is effective for treatment of rheumatoid arthritis. The person of ordinary skill in the art would have had a reasonable expectation of success in making the modification because it simply requires formulating a known amount of antibody when practicing the method of ‘818, and furthermore would have reasonably expected the treatment to be effective because polymyalgia rheumatica and rheumatoid arthritis are both rheumatic inflammatory diseases known to be treatable by targeting IL-6. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Claims 119 and 125 encompass a method of claim 1 (claim 119) or claim 97 (claim 125) wherein the antibody is administered subcutaneously using a needle and syringe.
The teachings of ‘818 that anticipate claims 1, 97, 118 and 123 are set forth above. Specifically, ‘818 teaches the method of treatment of independent claims 1 and 97, and further teaches subcutaneous administration as required by dependent claims 118 and 123. ‘818 does not teach that the subcutaneous administration is made by needle and syringe.
Boyapati teaches that the antibody of the invention, which is sarilumab, can be administered using a syringe and needle (¶ 198).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treatment of PMR by subcutaneously administering sarilumab taught by ‘818 and modify it to subcutaneously administer the sarilumab via a needle and syringe. The person of ordinary skill in the art would have been motivated to make such a change because ‘818 teaches subcutaneously administering sarilumab but does not further specify the means for subcutaneous administration, and Boyapati provides an art-recognized means for administering the same antibody for treatment. The person of ordinary skill in the art would have had a reasonable expectation of success in making the modification because it simply requires putting the antibody into a needle and syringe and using such for administration. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Claim 120 and 126 encompass a method of claim 1 (claim 120) or claim 97 (claim 126) wherein the antibody is administered using a prefilled syringe with “about 175 mg/ml sarilumab”.
The teachings of ‘818 that anticipate claims 1, 97, 118 and 123 are set forth above. ‘818 teaches the method of independent claims 1 and 97. ‘818 does not teach that the administration is made using a prefilled syringe containing about 175 mg/ml sarilumab.
Boyapati teaches administration of sarilumab using a prefilled syringe (¶ 60, 199-201), and that the administered solution may comprises “about 175 mg/mL of the antibody” (¶ 61).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to take the method of treatment of PMR by administering sarilumab taught by ‘818 and modify it to administer the sarilumab using a prefilled syringe containing about 175 mg/mL sarilumab as taught by Boyapati. The person of ordinary skill in the art would have been motivated to make such a change because ‘818 teaches administering sarilumab but does not further specify the means or concentration of sarilumab for administration, and Boyapati provides art-recognized means and concentration for administering sarilumab for treatment of disease. The person of ordinary skill in the art would have had a reasonable expectation of success in making the modification because it simply requires formulating a known amount of antibody when practicing the method of ‘818, and furthermore would have reasonably expected the treatment to be effective because polymyalgia rheumatica and rheumatoid arthritis are both rheumatic inflammatory diseases known to be treatable by targeting IL-6. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (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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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
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