Detailed Action
Applicants claims amendments filed 1/29/2026 are acknowledged and entered into the record.
Accordingly, Claims 19-29, 31-32, 38-44 are pending and will be examined on the merits.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections Maintained - 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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 19-29, 31-32, 38-44 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (Journal of Hematology and Oncology 2013, 6:36; cited on IDS filed 9/19/2023) as evidenced by the instant specification.
The claims are drawn to a method of treatment comprising administering a combination of an anti-CD19 antibody (XmAb5574, MOR00208) and a Bruton’s tyrosine kinase (BTK) inhibitor. The instant specification discloses “MOR00208” and “XmAb 5574” are used as synonyms to describe the antibody shown in Figures 4 and 5 (see page 9 of instant specification).
Wu et al. teach methods of treating chronic lymphocytic leukemia (CLL) with drugs such as dendamustine, ofatumumab, lenalidomide, ibrutinib, idelalisib, veltuzumab, XmAb5574, navitoclax, dasatinib, alvespimycin, and TRU-016. Wu et al. disclose “CLL is typically sensitive to a variety of cytotoxic drugs, but the disease is considered incurable. Treatment is generally recommended to control symptoms and reduce bulk of disease but without substantially improving survival. Emerging understanding of the molecular pathophysiology of CLL has facilitated the development of new drugs with a view to improving clinical outcomes for this malignancy”. Tables 1-6 of Wu et al. disclose single agents as well as combination therapy for treatment of CLL. One examples shows the combination of the BTK inhibitor, ibrutinib, with the anti-CD20 therapeutic antibody rituximab. Wu et al. disclose the following results ”A recent study however showed that high risk patients treated with ibrutinib plus rituximab had a higher ORR of 85%, and suggested additional development of ibrutinib for high-risk CLL patients”. Wu et al. further discloses results from treatment administering the anti-CD19 antibody instantly claimed stating “XmAb5574 showed tolerable toxicity profile and preliminary evidence of antitumor activity in high-risk patients with relapsed/refractory CLL. Based on the results of this study, a phase 2 study of this agent in patients with CLL and other B- cell malignancies is encouraged”. Wu et al. review several clinical trials using a combination of different agents to evaluate clinical efficacy. Wu et al. does not specifically teach the combination of the anti-CD19 antibody “XmAb5574” in combination with a BTK inhibitor (or the specific inhibitor ibrutinib) as instantly claimed.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use the anti-CD19 antibody “XmAb5574” in combination with a BTK inhibitor, such as ibrutinib, for the treatment of non-Hodgkin’s lymphoma including chronic lymphocytic leukemia (CLL) based on the teachings of Wu et al. One of ordinary skill in the art would have been motivated to use the agents in combination in a method of treatment in view of the clinical data presented in Wu et al. Each of these agents had been taught by the prior art to be effective against B-cell disorders such as CLL, thus the instant situation is amenable to the type of analysis set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980) wherein the court held that it is prima facie obvious to combine two modes of treatment, each of which is taught by the prior art to be useful for the same purpose in order to make a protocol that is to be used for the very same purpose since the idea of combining them flows logically from their having been individually taught in the prior art. Applying the same logic to the instant claims, given the teaching of the prior art of processes using either the anti-CD19 antibody “XmAb5574” or the BTK inhibitor, ibrutinib, in the process of CLL treatment, it would have been obvious to treat tumors with both, XmAb5574 and ibrutinib, because the idea of doing so would have logically followed from their having been individually taught in the prior art to be useful as agents for the same purpose. Furthermore, based on Wu’s disclosure of several ongoing clinical studies looking at a wide range of lymphomas including small and chronic lymphocytic lymphoma and other B-cell malignancies, one of ordinary skill in the art would be motivated to include the patient populations cited in instant claims 20-26. One of ordinary skill in the art would have reasonably expected to obtain effective treatment with either or both of these agents in these patient populations based on the prior art.
Additionally, although the prior art does not explicitly disclose the intervals instantly claimed "[w]here 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, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "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). Although the prior art does not explicitly teach the administration separately, simultaneously, etc as claimed, it would be conventional and within the skill of the art to identify the optional administered times. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method administer the same agents to achieve the same results. It would be conventional and within the skill of the art to determine the optimal administration regimens.
Response to Arguments
Applicant's argue in the response filed 1/29/2026 the unexpected results associated with the claimed invention would rebut the prima facie case of obviousness. Applicants argue the working examples of the present application describe experimental results for the combination of the MOR00208 antibody and a BTK inhibitor and unexpected properties that the inventors found to be associated with this combination. Applicants reference “Chou index curves” and “Clarke analysis” disclosed in the instant specification for showing synergistic combination of MOR00208 + ibrutinib, however these arguments are not commensurate in scope of the instant claims. The instant claims do not limit the BTK inhibitor to ibrutinib. The examples shown in the instant specification, and argued to have unexpected results, are specific to the combination of the MOR00208 anti-CD19 antibody and the specific BTK inhibitor ibrutinib. Applicant is invited to amend the claims to be commensurate in scope with the instant arguments.
Conclusion
Claims 19-29, 31-32, 38-44 are rejected.
No Claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Meera Natarajan/Primary Examiner, Art Unit 1643