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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 10, 2026 has been entered.
Applicant’s amendment filed on March 10, 2026 is acknowledged and entered.
Claims 1-2, 4-5, 7-8, 11-12, 14, 24, 27-32, 40, 42-44, 46-47, and new claims 51-52 are pending. Claims 2, 4, 9, 12, 14, 27-32 and 43 are withdrawn. Claims 3, 6, 10, 13, 15-23, 25-26, 33-39, 41, 45, 48-50 are canceled. Claims 1, 5, 7-8, 11, 24, 40, 42, 44, 46, 47, 49, 51-52 are examined
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph 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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 51 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the method claimed administering antibody comprising claim limitation of claim 1, does not reasonably provide enablement for the claimed method of administering generic sarilumab by name only. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and us the invention commensurate in scope with these claims.
The first paragraph of § 112 requires that the patent specification enable "those skilled in the art how to make and use the full scope of the claimed invention without `undue experimentation."' Genentech, Inc. v. Novo Nordisk AIS, 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)); see also In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). ("[T]he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art."). Whether making and using the invention would have required undue experimentation, and thus whether the disclosure is enabling is a legal conclusion based upon several underlying factual inquiries. See In re Wands, 858 F.2d 731, 735, 736-37, 8 USPQ2d 1400, 1402, 1404 (Fed. Cir. 1988). As set forth in Wands, the factors to be considered in determining whether a claimed invention is enabled throughout its scope without undue experimentation include the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art, and the breadth of the claims.
Likewise, in Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991), the court affirmed the holding of invalidity of claims to analogs of the EPO gene under § 112 for lack of enablement where applicants had claimed every possible analog of the EPO gene but had disclosed only how to make EPO and a very few analogs. "[D]espite extensive statements in the specification concerning all analogs of the EPO gene that can be made, there is little enabling disclosure of the particular analogs and how to make them .... There may be many other genetic sequences that code for EPO-type products. Amgen has told how to make and use only a few of them and is therefore not entitled to claim all of them." Id., 927 F.2d at 1213-14, 18 USPQ2d at 1027.
Claims encompass a method of inhibiting progression of radiographic structural damage to joints by administering generic sarilumab and function to increase from BL in mTSS score of at most 1 is achieved by week 52 because sarilumab claimed by name alone is not limited by structure. However, one skilled in the art cannot treat subject with generic sarilumab and achieve the function of mTSS score. The specification does not limit the term sarilumab as a single species and the specification on page 35 does not define the term and imply additional embodiments encompassed by the term. The specification does not teach the treatment any additional sarilumab. The amount of direction and example provided in the specification is limited to the specific species of sarilumab. One skilled in the art would require empirical experimentation in order to determine the treatment effect by the generic sarulimab whose structure is not limited. The state of the art is such that the treatment with methotrexate is unpredictable regarding the mTSS results (Rezaei et al. (Ann Rhem Dis, 2012); Ciubotariu et al., J. Rheumatol, 2014)). The state of the art is such that one skilled in the art cannot predict the outcome of treatment with generic sarilumab with unlimited structure and function in mTSS as claimed . No working example is provided for treatment with generic sarilumab with unlimited structural change and function as claimed except the specific species comprising the claimed SEQ ID NO:.
In view of the extent and the unpredictability of the experimentation required to practice the invention as claimed, one skilled in the art could not make the invention without undue experimentation. Therefore, based on the above Wands analysis, a preponderance of the evidence supports a conclusion that one skilled in the art would not have been enabled to make and use the claimed invention without undue experimentation.
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.
Claims 1, 3, 8, 11, 18-20, 24, 40, 42, 44, 46, 47, 51-52 are rejected under 35 U.S.C. 103 as being unpatentable over Clinical Trial NCT01061736 (2/3/2010) for the reasons of record set forth in the previous Office Actions mailed on 6/8/2023, 12/22/2023, 7/18/2024, 11/27/2024, 7/30/2025, 12/10/2025.
Clinical Trial NCT01061736 (NCT) discloses evaluation of sarilumab (SAR153191/REGN88) on top of methotrexate in rheumatoid arthritis patients (RA-MOBILITY), wherein the patients have been diagnosed with RA ≥3 months duration, and have at least 8/68 tender joints and 6/66 swollen joints (under “Inclusion criteria"); and received (one subgroup) sarilumab 200 mg SC injection q2w on top of MTX for a maximum of 52 weeks. NCT teach change from baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at 52 weeks, time frame is baseline and week 52, of radiographs to assess the degree of structural damage of erosions and joint space narrowing (page 4). NCT teach bone erosion based on documented D-ray prior to first study drug intake (page 11). Sarilumab inherently comprise the SEQ ID NO: claimed. NCT method of administration would inherently result in the increase from BL in modified Van der Heijde total Sharp (mTSS) score of at most 1 is achieved by week 52 after the initial dose of the antibody.
Therefore, it would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat RA with sarilumab with a dose 200 mg SC injection q2w, for example, and methotrexate following the teachings of Clinical Trial NCT01061736. The person of ordinary skill in the art would have been motivated to do so for disease treatment, and reasonably would have expected success because such has been used in the clinical trial. With respect to the limitation of “a subject having RA with a tender joint count of at least 27” recited in claims 1 and 20, it would have been obvious to treat such patients because the prior art reference teaches treating the patients having at least 8/68 tender joints, which include “at least 27”. The
NCT01061736 also teaches, as one of the “Primary Outcome Measures”, change from baseline in Van Der Heijde Modified Total Sharp Score (mTSS) was measured at week 52, which measure involves separate scores for erosions and joint space narrowing based on radiographs to assess the degree of structural damage (10th page, item 4.). Therefore, it would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to assess at baseline (and after the treatment) for radiographic structural damage to joints by mTSS, in order to monitor the RA disease stage/progression and response to the treatment, following the teachings of NCT01061736.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Applicants argue that the BL in mTSS score limitations are not inherent because the clinical trial protocol discloses only a planned study of sarilumab and methotrexate and provides no clinical results. The teaching of NCT is the same as the claimed administration methods and thus the results will be the inherently same. efficacy is not a requirement for prior art enablement (see MPEP 2121 III.); and a reasonable expectation of success is not equal to absolute certainty of success (efficacy data, for example), and obviousness does not require absolute predictability of success.
Applicants argue that Rezaei et al.support the evidence that structural damage inhibition is not an inevitable consequence of IL-6R blockage or RA treatment generally. However, the evidence is not with the treatment with Sarilumab but other treatments without sarilumab which does not support the inherent effect of sarilumab administration with methotrexate.
Claims 1, 5, 7, 8, 11, 24, 40, 42, 44, 46, 47, 51-52 are rejected under 35 U.S.C. 103 as being unpatentable over Radin et al. (US 8,080,248, 12/20/2011; or its application US 2010/0316636, 12/16/2010; provided by applicants), and as evidenced by Jasson et al. (US 2013/0149310, 6/13/2013; provided by applicants), further in view of Clinical Trial NCT01061736 (2/3/2010, provided previously), for the reasons of record set forth in the previous Office Actions mailed on 5/26/2022, 12/23/2022, 6/8/2023, 12/22/2023, 7/18/2024, 11/27/2024, 7/30/2025, 12/10/2025.
Radin discloses methods of treating rheumatoid arthritis using a fully human antibody or antigen-binding fragment thereof that specifically binds human interleukin-6 receptor (hIL-6R), wherein the antibody comprises the VH of SEQ ID NO:19 and VL of SEQ ID NO:27 (abstract, and claim 1, for example), which are 100% identical to the present SEQ ID NO:2 and 3, respectively. As evidenced by Jasson, sarilumab is an antibody comprising the heavy chain variable region of SEQ ID NO:2 and the light chain variable region of SEQ ID NO:3 (page 9, [0163]), which are 100% identical to the present VH of SEQ ID NO:2 and VL of SEQ ID NO:3, respectively. Additionally, Radin teaches that the methods include administering multiple doses of an anti-hIL-6R antibody to a patient over a specified time course, and the therapeutically effective amount can be about 50 mg to 200 mg (the paragraph bridging columns 8 and 9, and claim 8, for example). Further, Radin teaches that the antibody can be administered subcutaneously, and can be combined with one or more additional therapeutic agents, including methotrexate and sulfasalazine (column 5, lines 21-25, and column 11, last paragraph). Furthermore, Radin teaches specific examples of the clinical studies, wherein the regimens for treating RA patients include using the IL-6R antibody with concomitant methotrexate (MTX), wherein 150 mg the IL-6R antibody is administered SC every other week, and MTX is administered at a dose of 7.5 to 25 mg/week (columns 27-28, Example 11, esp. col. 27, lines 26-29 and 45-46, for example). Radin does not teach a treatment of at least 52 weeks.
Clinical Trial NCT01061736 (NCT) discloses a clinical trial study of evaluation of sarilumab (SAR153191/REGN88) on top of methotrexate (MTX) in rheumatoid arthritis patients (RA-MOBILITY), wherein a group of the RA patients received (one subgroup) sarilumab 200 mg SC injection q2w on top of MTX for a maximum of 52 weeks (pages 1 and 8, for example). As evidenced by Jasson, sarilumab is an antibody comprising the heavy chain variable region of SEQ ID NO:2 and the light chain variable region of SEQ ID NO:3 (page 9, [0163]), which are 100% identical to the present VH of SEQ ID NO:2 and VL of SEQ ID NO:3, respectively.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to treat RA with sarilumab at a dose 150 mg or 200 mg SC injection q2w for 52 weeks (for example), and methotrexate at a dose of 7.5 to 25 mg/week, following the teachings of Radin and NCT01061736. The person of ordinary skill in the art would have been motivated to do so for disease treatment, and reasonably would have expected success because Clinical Trial NCT01061736 specifically teaches such a regimen.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Applicants argument filed on March 10, 2026 has been fully considered, but is not deemed persuasive for the reasons below.
At pages 11-12 of the response, the applicant made similar argument as previously and above: Radin does not teach or suggest a method to inhibit progression of radiographic structural damage to joints in "a subject who is determined to have RA and who is assessed at baseline for radiographic structural damage to joints by mTSS as claimed; and Jasson and the clinical trial study do not overcome Radin's deficiencies; and applicants rely on their discussion above as it relates to the clinical trial study; the Office has not shown that Jasson teaches or suggests methods that would be particularly useful for inhibiting progression of radiographic structural damage to joints of a specific subpopulation of RA patients as recited in the present claims; improvement in ACR or DAS28 scores does not necessarily equate with inhibition of radiographic progression of structural damage, and a person skilled in the art would not reasonably expect that treatment improving these scores would necessarily result in a change in mTSS scores; and even if clinical improvement is observed does not mean that the radiographic structural damage is improved, as discussed above.
This argument is not persuasive for the reasons of record and above.
Double Patenting Rejections:
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 8, 11, 24, 40, 42, 44, 46, 47, 51-52 remain rejected, and the new claim 49 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-7 of U.S. Patent No. 7,582,298 in view of Clinical Trial NCT01061736 (2/3/2010), for the reasons of record set forth in the previous Office Action mailed on 2/26/2019, at page 10; and for the reasons above, as explained under “Prior Art Rejections”.
Claims 1, 8, 11, 24, 40, 42, 44, 46, 47, 51-52 remain rejected, and the new claim 49 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 9,173,880 or over claims 1-26 of U.S. Patent No. 10,072,086, in view of Clinical Trial NCT01061736 (2/3/2010), for the reasons of record set forth in the previous Office Action mailed on 2/26/2019, at pages 10-11; and for the reasons above.
Claims 1, 8, 11, 24, 40, 42, 44, 46 and 47 remain rejected, and the new claim 49 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,098,127 in view of Clinical Trial NCT01061736 (2/3/2010), for the reasons of record set forth in the previous Office Action mailed on 2/26/2019, at page 11; and for the reasons above.
Claims 1, 8, 11, 24, 40, 42, 44, 46, 47, 51-52 remain rejected, and the new claim 49 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3 of U.S. Patent No. 8,080,248 in view of Clinical Trial NCT01061736 (2/3/2010), for the reasons of record set forth in the previous Office Action mailed on 2/26/2019, at page 11; and for the reasons above.
Claims 1, 8, 11, 24, 40, 42, 44, 46, 47, 51-52 remain rejected, and the new claim 49 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 8,192,741 or over claim 3 of U.S. Patent No. 8,568,721 or over claims 2 and 9 of U.S. Patent No. 9,308,256, in view of Clinical Trial NCT01061736 (2/3/2010), for the reasons of record set forth in the previous Office Action mailed on 2/26/2019, at page 11; and for the reasons above.
Claims 1, 8, 11, 24, 40, 42, 44, 46, 47, 51-52 remain rejected, and the new claim 49 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-13 of U.S. Patent No. 9,943,594 in view of Clinical Trial NCT01061736 (2/3/2010), for the reasons of record set forth in the previous Office Action mailed on 2/26/2019, at pages 11-12; and for the reasons above.
Claims 1, 8, 11, 24, 40, 42, 44, 46, 47, 51-52 remain rejected, and the new claim 49 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,927,435 (claims 1, 4, 5, 9-11 and 22-33 of the copending Application No. 14/350,973 in the previous provisional nonstatutory double patenting rejection) in view of Clinical Trial NCT01061736 (2/3/2010), for the reasons of record set forth in the previous Office Action mailed on 2/26/2019, at page 12; and for the reasons above.
Claims 1, 8, 11, 24, 40, 42, 44, 46, 47, 51-52 remain provisionally rejected, and the new claim 49 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 10-14, 16-18 and 21-31 of copending Application No. 15/910,733, in view of Clinical Trial NCT01061736 (2/3/2010), for the reasons of record set forth in the previous Office Action mailed on 2/26/2019, at page 12; and for the reasons above.
Applicants argument filed on March 10, 2026 has been fully considered, but is not deemed persuasive for the reasons below.
Applicant made similar arguments for above rejections: the claims of these patents, alone or combined with the clinical trial study, do not teach or suggest the claimed method; the clinical trial study fails to cure the deficiencies of the claims of those patents; as discussed above, the clinical trial study at least fails to teach, or suggest a subject who is determined to have rheumatoid arthritis and who is assessed at baseline for radiographic structural damage to joints by mTSS", and that "the subject achieves, after at least 52 weeks of treatment, a change of at most 1 in mTSS score from the baseline".
This argument is not persuasive for the reasons of record and above (including that discussed in the prior art rejections).
No claims are allowed.
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/MICHAEL D PAK/Primary Examiner, Art Unit 1674
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