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 .
1. Formal Matters
Claims 32-67 are pending and are the subject of this Office Action.
2. Specification
A. The first line of the specification should be updated to reflect the status (e.g. “now U.S. Patent No.”, or “now abandoned”) of any parent applications. Similarly, though none could be found, any U.S. or Foreign Applications cited in the specification which have since issued should be updated with the corresponding Patent No.
B. The specification has not been checked to the extent necessary to determine the presence of all possible minor errors, embedded hyperlinks, or improperly referenced trademarks. Applicants’ cooperation is requested in correcting any errors of which Applicants may become aware.
3. Claim Objections
A. Claim 36 is objected to since it should end with the word “reaction”.
B. In claims 40, 56 and 66, it is believed that the word “a” should be added before “glucocorticoid”.
4. 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.
A. Claims 32-38, 40, 42 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al.
The claims are essentially drawn to a method of reducing an adverse IRR in a subject administered amivantamab. Park teaches the recommended doses recited in claim 37 as well as how to manage all 4 grades of amivantamab IRR –
As of 8 Jun 2020, 258 pts have received amivantamab at the RP2D. IRR was reported in 167 pts (65%) and was characterized by dyspnea, flushing, chills, and nausea. IRR severity was mostly grade 1–2; grade 3 IRR occurred in 5 pts, and 1 had a grade 4 event. Median time to IRR onset was 44mins, with 94% occurring on cycle 1, day 1 (C1D1); only 1 event occurred ≥C2. Of the 167 pts with IRR, 134 completed the full split dose and continued treatment per schedule; 33 pts (13%) aborted C1D1 infusion due to IRR, of which 4 discontinued further therapy. Per protocol, IRRs were mitigated on C1D1 with holding of infusion (54%) and reinitiating at a reduced rate (50%). Translational studies in a subset of pts measuring 22 circulating analytes (e.g., markers of cytokine release syndrome, mast cell degranulation, tumor lysis syndrome, complement activation) failed to distinguish a pattern between pts with and without IRR.
The only difference is that Park does not state increasing the infusion rate if there are no additional adverse reactions after 30 minutes. However, it would have been obvious at the time to monitor infusion and increase to the originally administered dose since this would have been calculated as the optimal dose for treatment. Furthermore, where 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, 454, 105 USPQ 223,235, (CCPA 1955). Furthermore, "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and, therefore, obvious) and E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018) (“it is not inventive to discover the optimum or workable ranges by routine experimentation.”).
B. Claims 39 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. in view of Laudati et al. The teachings of Park are seen above. Park does teach “[f]or all doses, pre-infusion antihistamines and antipyretics were required; steroids were optional after initial dose”. Park does not teach specific premedications.
However, Laudati does. Though, Laudati teaches rituximab instead of amivantamab, page 4 of Laudati teaches that acetaminophen, diphenhydramine and dexamethasone are standard premedications -
First-dose rituximab was administered starting at 50mg/hour and titrated by 50mg/hour increments every 30 minutes, to a maximum rate of 400mg/hour. Patients received standard premedications of acetaminophen 650mg and diphenhydramine 50mg intravenously. Patients receiving a chemotherapy-containing regimen received Dexamethasone 12mg in addition to acetaminophen and diphenhydramine as standard premedication. Investigators noted non-standard premedication administration when hydrocortisone was added to the regimen, or doses of acetaminophen and/or diphenhydramine were modified by provider.
C. Claims 44-54, 56, 58-62, 64 and 66, are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. While this rejection could have been incorporated into paragraph A of this section, it has been separated for clarity.
The teachings of Park are seen above. Park teaches IRR, including the premedications in claims 54, 56, 64 and 66. However, Park dose not teach reducing an adverse reaction to a subject suspected of experiencing an interstitial lung disease/pneumonitis (claim 44), a dermatologic reaction (claim 48), or and other adverse event (claim 58).
However, it would have been obvious at the time of the instant invention to have withheld or discontinued amivantamab (in addition to possible reevaluation) if any serious side effect had been seen (e.g. claims 44, 48, 50, 58-61). Regarding claim 44, it is also noted that, without a claimed time period to restart treatment, “withholding” and “discontinuing” are identical.
Regarding claims 49 and 50, see the case law recited in paragraph A, above.
Regarding claim 53, Park (Methods) teaches reducing/splitting the first dose during an IRR. See also the above-cited case law.
D. Claims 55, 57, 65 and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. in view of Laudati et al. The teachings of Park and Laudati are seen in paragraph B of this section.
5. Conclusion
No claim is allowable.
Advisory information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S LANDSMAN whose telephone number is 571-272-0888. The examiner can normally be reached M-F 8 AM – 6 PM (eastern).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647
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