DETAILED ACTION
1. Please note the Examiner of record has changed. Contact information is provided at the close of this Action.
Notice of Pre-AIA or AIA Status
2. 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
3. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 15, 2026 has been entered.
4. Claims 36, 42, 43, 45, 46, 59-61, 63, 64, 67, 71, 76-78, 80 and 81 are pending.
Claims 52 and 79 have been cancelled.
Claims 36, 46, 60, 61, 63 and 80 have been amended.
Claim 81 has been added.
Claims 36, 42, 43, 45, 46, 59-61, 63, 64, 67, 71, 76-78, 80 and 81 are examined on the merits.
5. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Withdrawn Grounds of Rejection
Claim Rejections - 35 USC § 112
6. The rejection of claim 80 for the phrase "at a dose that is lower than a starting dose" recited in item "(A)" is withdrawn in light of the amendment to the claim further clarifying the phrase, see Amendments to the Claims submitted April 5, 2026, page 5.
Claim Rejections - 35 USC § 102
7. The rejection of claim(s) 36, 42, 45, 61, 63, 64, 72-78 and 80 under 35 U.S.C. 102(a)(1) as being anticipated by Emery et al., (Ann. Rheum. Dis 67:1516-1523, published online first 14 July 2008) is withdrawn in light of Applicant’s arguments set forth in the Remarks submitted April 15, 2026, page 8, paragraphs (paras.) 3 and 4. Claims 52 and 79 have been cancelled.
8. The rejection of claim(s) 36, 42, 45, 61, 63, 64, 72-78 and 80 under 35 U.S.C. 102(a)(1) as being anticipated by Emery et al., (Ann. Rheum. Dis 67:1516-1523, published online first 14 July 2008) is withdrawn in light of Applicant’s arguments set forth in the Remarks submitted April 15, 2026, page 9, 4th paragraph (para.). Claims 52 and 79 have been cancelled.
9. The rejection of claims 36, 42, 45, 63-64, 67, 71 and 80 are newly rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burmester et al. (Annals of the rheumatic diseases, 73(1): 69-74, published online first 8 June 2015/ IDS filed 02/26/2024) is withdrawn in light of Applciant’s arguments set forth in the Remarks submitted April 15, 2026, paragraph bridging pages 9 and 10. Claim 52 has been cancelled.
10. The rejection of claim 43 under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Emery et al. 2008 (Annals of the rheumatic diseases, 67(11), 1516- 1523.; IDS filed 02/26/2024), as applied to Claim 36 above, and as evidenced by NCT00106522 (ClinicalTrials.gov ID NCT00106522; of record), and NCT01011959 (ClinicalTrials.gov ID NCT01011959; of record) is withdrawn in light of the fact Emery falls noted previously due to Applicant’s arguments submitted April 15, 2026, see pages 8 and 10 of the Remarks.
Claim Rejections - 35 USC § 103
11. The rejection of claims 46 and 59 under 35 U.S.C. 103 as being unpatentable over Emery et al. 2008 (Annals of the rheumatic diseases, 67(11), 1516-1523.; IDS filed
02/26/2024), as applied to Claim 36 above is withdrawn in light of the arguments submitted April 15, 2026, see Remarks, pages 10 and 11.
12. The rejection of claims 76-78 under 35 U.S.C. 103 as being unpatentable over Pappas et al. (Rheumatology and Therapy 3(1): 103-115, published online: February 8, 2016).
New Objection
Claim Objections
13. Claims 36 and 80 are objected to because of the following informality: both claims recite roman numerals and alphabets with a period. MPEP 680.01(m) states “[e]ach claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995).”
Correction is required.
New and Maintained Grounds of Rejection
Claim Rejections - 35 USC § 103
14. 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.
15. Claim(s) 36, 42, 43, 45, 46, 59-61, 63, 64, 67, 71-78, 80 and new claim 81 is/are rejected under 35 U.S.C. 103 as being unpatentable over Emery et al., (Ann. Rheum. Dis 67:1516-1523, published online first 14 July 2008), and further in view of Pincus et al. (Rheumatology 41: 1346-1356, 2020) and Pappas et al. (Rheumatology and Therapy 3(1): 103-115, published online: February 8, 2016).
Applicant pre-emptively argues the formerly cited documents set forth in the Final Action mailed January 15, 2026 doe not disclose or suggest the claimed invention, see Remarks submitted April 15, 2026, page 13, last two paragraphs (paras.). However, herein is a new combination of references does teach the claimed invention set forth in claim 31 as stated herein.
Applicant also argues secondary reference, “Pappas is a retrospective, observational analysis of real-world dose escalation patterns of intravenous tocilizumab in the United States”, not disclosing, teaching or suggesting the claimed invention, see page 12 of the Remarks, 4the paragraph (para.).
Applicant further asserts Pappas “addresses post-initiation dose adjustment”, which is different from the “…pre-treatment method that conditions initiation of a starting dose on a defined corticosteroid-free interval”, see para. bridging pages 12 and 13. However, herein with the instant combination of references these assertions are not persuasive.
Emery teaches a method of treating rheumatoid arthritis (RA) in patients refractory to tumor necrosis factor antagonist therapy comprising administering 8 mg/kg tocilizumab intravenously every 4 weeks, see Abstract; and Figure 1 on page 1518.
Emery teaches that prior therapy at baseline was anti-TNF therapy (i.e. patients had not previously been administered tocilizumab), see Table 1 on page 1517. “ Patients discontinued etanercept (⩾2 weeks), infliximab or adalimumab (⩾8 weeks), leflunomide (⩾12 weeks) and all DMARD other than methotrexate before receiving study medication. Patients had to be treated with methotrexate for 12 weeks or more before baseline (stable dose ⩾8 weeks).”, see page 1516, 2nd column, last full paragraph (para.).
Emery teaches that the selected patients were “…18 years of age and older with moderate to severe active RA…”, page 1516, 2nd column (col.), Patients segment, 1st sentence. Eighty-four percent of the patients were female, see page 1517, Table 1.
Emery teaches that patients with malignancies and inflammatory diseases other than rheumatoid arthritis were excluded, thus reading on the diseases and disorders cited in claim 45, see para. bridging pages 1516 and 1517.
Emery teaches that 64.7% of the patients did not have anemia prior to tocilizumab treatment, see Table 1 on page 1517, wherein 35.3% below lower limit of normal haemoglobin).
Emery teaches that patient is also administered methotrexate concomitant with the tocilizumab, see Abstract. "All patients received stable methotrexate (10-25 mg weekly)”, see page 1517, 1st col., Study design, 1st para.
Emery teaches the patients previously had an inadequate response to TNF antagonists (i.e. DMARDs) including etanercept, adalimumab, and infliximab, see Abstract on page 1516; Patients and Methods spanning pages 1516-1518; and Table 1 on page 1517.
Absent evidence to the contrary, the subject has not received sarilumab.
Emery does not teach the subject has not been administered a corticosteroid within 90 days of the starting dose, wherein the corticosteroid is prednisone.
However, Pincus teaches RA without the administration of corticosteroids including prednisolone. Prednisolone is art known to be the active form of prednisone. Pincus also does not particularly point out the ages of those patients that received an escalated dose prior to three months.
Pappas teaches a study assessing real-world instances of dose escalation in patients with RA treated with tocilizumab (TCZ), Abstract on page 103. Pappas teaches that the recommended starting dose of intravenous (IV) TCZ for the treatment of RA varies around the world, and that the recommended starting dose in Japan and European countries is 8 mg/kg every 4 weeks (Q4W), see page 104, 2nd col., 1st para. Pappas teaches the recommended starting dose for IV TCZ in the United States is 4 mg/kg Q4W, but that "(t)he dose may be increased to 8 mg/kg based on clinical response, at the physician's discretion", see page 104, 2nd col., 1st para.
Pappas highlights that "(t)he ability to administer TCZ in varying doses allows physicians to tailor TCZ therapy to disease activity", see Abstract on page 103; and Conclusions on page 113. Pappas teaches that 53.1% of patients included in the study were escalated to the 8 mg/kg dose at or before 3 months with greater than 70% of all patients having been escalated to the 8 mg/kg dose by 6 months, see TCZ Dosing Patterns on page 106; and Figure 107 on page 107.
Pappas teaches that prior studies suggest that a higher proportion of patients receiving TCZ 8 mg/kg achieved a response by 6 months, and "the option to adjust TCZ dose based on individual clinical responses may have provided an additional benefit to the patients" (Pg. 110). Pappas teaches that dose escalation occurring prior to 3 months included any time during said period and "could have occurred very close to the baseline visit or very close to the 3-month visit".
It would have been obvious to one of ordinary skill in the art before the effective
filing date of the claimed invention to combine teachings of Emery, Pincus and Pappas to treat the RA patient with no corticosteroids while administering the starting dose of TCZ as set forth in Emery because such treatments are implemented as taught in Pincus as it is know that corticosteroids are known to render undesirable side-effects, see page 1351, Corticosteroids and in particular 2nd col.
It also would have been obvious to one of ordinary skill in the art that the discretionary TCZ dose escalation from 4 mg/kg to 8 mg/kg before three months as taught by Pappas could be performed at any time prior to 3 months (including at 2 months, 1 month, or sooner) and could be applied to any patient, including those aged 18-34 and at the initiation of a started dose on a defined corticosteroid-free interval.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success not to administer the corticosteroids within 90 days of the starting dose of TCZ to critically assess the inflammatory activity of the patient’s RA, as well as to establish which RA drugs are efficacious or not, see Pincus in its entirety and primary reference, Emery and Pappas in their entireties.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because Pappas teaches that the majority of patients elect to increase from 4 mg/kg to 8 mg/kg at or prior to 3 months, because Pappas teaches that the so-called "escalated" dose is the same as the recommended starting dose in many places outside the United States, and because Pappas teaches "the option to adjust TCZ dose based on individual clinical responses may have provided an additional benefit to the patients"., see page 110, para. bridging both columns.
Conclusion
16. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached on 8AM-8PM, Monday through Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
14 September 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643
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