DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant's amendment and remarks filed on 06/15/2023 are acknowledged.
Claims 1-4, 8-12, 14, 22-25 and 29-33 are pending.
3. Claim 25 is objected to because of an apparent typographical error in the phrase “once every two we.” Appropriate correction or clarification is required.
4. 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.
5. Claims 1-4, 8-12, 14, 22-25 and 29-33 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claims 1 and 22 are indefinite in the recitation of “non-inflammatory pain” in subject with rheumatoid arthritis. Rheumatoid arthritis is characterized by joint inflammation and joint pain; therefore, specific criteria are required to distinguish non-inflammatory pain from pain associated with inflammation in rheumatoid arthritis patients.
The specification does not appear to provide a sufficiently specific, limiting definition of non-inflammatory pain in rheumatoid arthritis patients.
The specification provides the following description:
The term “non-inflammatory pain” or “NIP” refers to pain not associated with inflammation, as described above. In some cases, the NIP may be due to arthralgia or polyarthralgia. NIP typically presents with an absence of systemic symptoms such as fever or weight loss. NIP can also present without swelling or warmth. NIP can also be characterized by minimal morning stiffness which is intermittent, lasts less than 60 minutes and/or stiffness which is made worse, not improved, by activity. In some embodiments, NIP includes acute or chronic pain. In some embodiments, NIP includes allodynia, enhanced pain and neuropathic pain. In some embodiments, a subject with NIP also is experiencing central sensitization. In some embodiments, subjects with NIP are earlier in the course of RA. In some embodiments, these subjects have not been diagnosed with RA and do not show symptoms of inflammation. In some embodiments, subjects with NIP have extra-articular or diffuse pain. ([0020] of US 20230192871 (cited on IDS), corresponding to p. 6-7 of the specification as filed).
This description is non-limiting and exemplary, and as such is insufficient to define the term as used in the claims.
The specification further discloses:
In some embodiments, NIP is defined as a difference between the 28-joint tender joint count (TJC) and swollen joint count (SJC), using the established formula: TJC−SJC≥7. [0027]
This definition is deemed sufficiently specific, and if incorporated as a limitation into the claims may be sufficient to satisfy the requirements of 35 U.S.C. 112(b).
(ii) Claims 3 and 24 are indefinite in the recitation “the tender joint count differs from a swollen joint count by at least 5,” because it is unknown whether the tender joint count is higher by 5 or lower by 5 than the swollen joint count.
(iii) Claim 4 is indefinite because, in the absence of a conjunction (such as e.g. “and” or “or”) in the listing of the three subclauses, it is unclear whether the claim requires that all three recited conditions be fulfilled, or any one condition may be fulfilled.
(iv) Claims 2-4, 8-12, 14, 23-25 and 29-33 are indefinite, because they encompass the indefinite limitations of the claim(s) on which they depend.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
6. The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
7. Claims 11-12 and 32-33 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contain(s) subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not provide a sufficient enabling description of a method comprising administering to subjects with rheumatoid arthritis the recited anti-IL-6R antibody in combination with a TNF antagonist.
The specification does not enable one of skill in the art to make and use the invention as claimed without undue experimentation. Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized in In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, limited working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to make and use the claimed invention.
As disclosed in the specification, anti-IL-6R antibody sarilumab comprises SEQ ID NOS: 1-8 recited in instant claims (e.g. [0067]). Sarilumab is also known as Kevzara®.
The specification cites clinical studies of sarilumab in rheumatoid arthritis patients (Example 1), but does not appear to provide specific guidance, direction, or working examples of using sarilumab in combination with TNF antagonists.
FDA-approved label for Kevzara® revised on 04/2018 (“the Label”) was the current label at the effective filing date of the present application. The Label provides the following guidance (subsection 2.2, General Considerations for Administration):
“Avoid using KEVZARA with biological DMARDs because of the possibility of increased immunosuppression and increased risk of infection. The concurrent use of KEVZARA with biological DMARDs such as TNF antagonists, IL-1R antagonists, antiCD20 monoclonal antibodies and selective co-stimulation modulators has not been studied.”
Based on FDA guidance, and given the absence of relevant direction or examples in the present disclosure, a skilled artisan would reasonably conclude that administering sarilumab in combination with a TNF antagonist to subjects with rheumatoid arthritis would be improper and undue.
8. 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.
9. Claims 1-4, 8-10, 14, 22-25 and 29-31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kevzara® FDA Label revised 04/2018 (“the Label”).
Kevzara® is the brand name of sarilumab, an anti-IL-6R antibody comprising SEQ ID NOS: 1-8 recited in instant claims.
According to the Label, sarilumab is indicated for treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs) (p. 1).
Regardless of how non-inflammatory pain (NIP) in subjects with rheumatoid arthritis is defined (see subsection 5.1 above), administration to subjects with rheumatoid arthritis is within the scope of claim 1, since there is no manipulative difference between the treatment indicated by the Label and the claimed method.
Claim 22 recites the steps of (i) selecting a subject who has rheumatoid arthritis and NIP; and (ii) administering to the subject the specified antibody. It would be readily understood by those skilled in the art that subject who have rheumatoid arthritis but not NIP (however defined) will not be denied treatment, i.e. will also be treated as indicated by the Label. Therefore, the step of selecting subjects with NIP does not result in a manipulative difference between the claimed method and the treatment indicated by the Label.
Furthermore, Table 5 of the Label provides information about two clinical studies of sarilumab, wherein at baseline, the mean numbers of tender and swollen joints in study subject were as follows:
Tender Swollen Difference
Study 1, Group 1: 27.21 16.60 10.61
Study 1, Group 2: 26.50 16.77 9.73
Study 2, Group 1: 27.66 19.60 8.06
Study 2, Group 2: 29.55 19.97 9.58
Accordingly, typical subjects of these studies had a tender joint count of at least 26, and the tender joint count differed from swollen joint count by at least 8, which is within the scope of instant claims 3 and 24, as well as the definition provided at paragraph [0027] of the specification.
Further, according to the Label at p. 1, the recommended dosage of sarilumab is 200 mg once every two weeks, administered as a subcutaneous injection. Sarilumab may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs.
Accordingly, the Label teaches all of the limitations of claims 1-4, 8-10, 14, 22-25 and 29-31, and as such anticipates these claims.
10. Conclusion: no claim is allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILIA I OUSPENSKI whose telephone number is (571)272-2920. The examiner can normally be reached 8:30 AM – 5 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel Kolker can be reached at 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644