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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/22/2026 has been entered.
Claims 1, 3-5, 8, and 10-15 are now pending and under prosecution.
Maintained Rejection
(Arguments Addressed)
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.
Claim(s) 1 and 3-5 remain rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (WO2018033135 A1; Published 2/22/2018; cited in IDS 5/8/2023), in view of Wilson et al. (Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015;21(8):922-926; of record).
Wang teaches the use of a BTK inhibitor (instantly claimed Compound 1; see image below), and teaches that this agent is used for the treatment of cancers, and has potent, irreversible activities against Btk. [0005-0006] Regarding claims 3-5, Wang teaches and demonstrates that the Btk inhibitor is administered at dose of 320 mg daily or 160 mg twice daily. [0099] Wang further demonstrates that Compound 1 is administered at 320 mg once daily or 160 mg twice daily in 28-day cycles. [Example 8, 0134, Claims 28 and 29] Wang teaches that the cancer treated is diffuse large B cell lymphoma (DLBCL), specifically, non-germinal center-B-cell diffuse large B-cell lymphoma (non-GCB DLBCL) [0014), or activated B-cell large B-cell lymphoma (ABC-DLBCL). [0015, 0063] Wang teaches that the Compound 1 was shown to be active as treatment alone. [0106] Wang teaches that Compound 1 is a more selective BTK inhibitor compared to ibrutinib. [0131]
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Compound 1 of Wang
However, Wang does not teach that the patient treated is characterized by a CD79B mutation.
Wilson teaches a method for treating a human patient with GCB diffuse large B cell lymphoma (DLBCL), the method comprising administering to the human patient, a BTK inhibitor ibrutinib. [pg 7, treatment and evaluation] Wilson teaches assaying for gene expression of CD79B mutation in a cancer sample obtained from the patient; [pg 7, molecular analysis and in vitro studies; pg 3] Wilson teaches that increased expression of CD79b mutation indicates that the patient will be sensitive to BTK inhibitor treatment. Wilson specifically teaches that the response rate was 55% and significant tumor reductions, and patients with increased expression of CD79b responded more frequently to the BTK inhibitor. [pg 3, third paragraph]
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to treat non-GCB DLBCL with Compound 1 in a patient characterized by a CD79B mutation. One would have been motivated to, and have a reasonable expectation of success, because: (1) Wang teaches a method of treating non-GCB diffuse large B-cell lymphoma comprising administering Compound 1, a BTK inhibitor, (2) Wilson teaches a method of treating DLBCL comprising administering a BTK inhibitor and teaches that increased expression of CD79B mutation results in an increase response rate and significant tumor reduction, and that patients with this mutation responded more frequently to the BTK inhibitor. Given the known use of Btk inhibitors for the treatment of DLBCL, specifically non-GCB DLBCL, and given the known response of BTK inhibitors in individuals with CD79B mutations, one of skilled in the art could have pursued treating non-GCB DBLCL in patients with a CD79B mutations with Compound 1, with a reasonable expectation of success.
Claim(s) 8, 10-15 remain rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (WO2018033135 A1; Published 2/22/2018; cited in IDS 5/8/2023), in view of Wilson et al. (Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015;21(8):922-926; of record), and Klein et al (US20150125446 A1; Published 5/7/2015).
Wang teaches the use of a BTK inhibitor (instantly claimed Compound 1; see image below), and teaches that this agent is used for the treatment of cancers, and has potent, irreversible activities against Btk. [0005-0006] Regarding claims 3-5, Wang teaches and demonstrates that the Btk inhibitor is administered at dose of 320 mg daily or 160 mg twice daily. [0099] Wang further demonstrates that Compound 1 is administered at 320 mg once daily or 160 mg twice daily in 28-day cycles, in combination with an anti-CD20 antibody. [Example 8, 0134, Claims 28 and 29] Wang teaches that the cancer treated is diffuse large B cell lymphoma (DLBCL), specifically, non-germinal center-B-cell diffuse large B-cell lymphoma (non-GCB DLBCL) [0014), or activated B-cell large B-cell lymphoma (ABC-DLBCL). [0015, 0063] Wang teaches that the Compound 1 was shown to be active as treatment alone. [0106] Wang teaches that Compound 1 is a more selective BTK inhibitor compared to ibrutinib. [0131]
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Compound 1 of Wang
However, Wang does not teach that the patient treated is characterized by a CD79B mutation.
Wilson teaches a method for treating a human patient with GCB diffuse large B cell lymphoma (DLBCL), the method comprising administering to the human patient, a BTK inhibitor ibrutinib. [pg 7, treatment and evaluation] Wilson teaches assaying for gene expression of CD79B mutation in a cancer sample obtained from the patient; [pg 7, molecular analysis and in vitro studies; pg 3] Wilson teaches that increased expression of CD79b mutation indicates that the patient will be sensitive to BTK inhibitor treatment. Wilson specifically teaches that the response rate was 55% and significant tumor reductions, and patients with increased expression of CD79b responded more frequently to the BTK inhibitor. [pg 3, third paragraph]
Klein teaches known combinations of anti-CD20 antibodies with BTK inhibitors, for the treatment of cancer, including ABC-DLBCL. [0011, 0012, 0157; Example 1] Klein further teaches that the antibody may be rituximab, [0016] or obinutuzumab [0102]
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to treat non-GCB DLBCL with Compound 1 in a patient characterized by a CD79B mutation. One would have been motivated to, and have a reasonable expectation of success, because: (1) Wang teaches a method of treating non-GCB diffuse large B-cell lymphoma comprising administering Compound 1, a BTK inhibitor,(2) Wilson teaches a method of treating DLBCL comprising administering a BTK inhibitor and teaches that increased expression of CD79B mutation results in an increase response rate and significant tumor reduction, and that patients with this mutation responded more frequently to the BTK inhibitor, (3) Wang and Klein both teach the combination of a BTK inhibitor with an anti-CD20 antibody, such as rituximab or obinutuzumab, and (4) Wang specifically teaches and demonstrates that the combination of Compound 1 with an anti-CD20 antibody significantly increases anti-tumor response. Given the known use of Btk inhibitors for the treatment of DLBCL, specifically non-GCB DLBCL, given the known response of BTK inhibitors in individuals with CD79B mutations, and given the known methods of combining an anti-CD20 antibody and a BTK inhibitor, one of skilled in the art could have pursued treating non-GCB DBLCL in patients with a CD79B mutations with Compound 1 and an anti-CD20 antibody, with a reasonable expectation of success.
Response to Relevant Arguments
Applicants argue that the references do not provide a motivation to combine. Applicant argues that Wang discloses the claimed Compound 1 but is silent regarding CD79B mutation. Applicant argues that Wilson discloses a structurally distinct BTK inhibitor and reports patients with CD79B mutation responded more frequently to that BTK inhibitor. Applicant argues that Wilson does not suggest its findings to apply to other BTK inhibitors and only discloses the use of ibrutinib. Applicant argues that the references do not provide a reasonable expectation of success. Applicant argues that BTK inhibitors are not interchangeable. Applicant argues unexpected superior results and points to Examples 4A and 4B.
Applicant’s arguments have been considered but are not persuasive. The claims are drawn to a method for treating non-GCB DLBCL comprising administering Compound 1, wherein the patient is characterized by a CD79B mutation. The Examiner relied on the combination of references to render the method obvious. The primary reference, Wang, teaches the use of Compound 1, which is a BTK inhibitor, and teaches that this is used for the treatment of cancers, including non-GCB DLBCL. Wang teaches that this compound is active as monotherapy, and teaches that this is BTK inhibitor is more active/selective compared to ibrutinib, which is another BTK inhibitor. Although Wang does not teach that the patient has a CD79B mutation, Wang teaches and exemplifies the activity of this BTK inhibitor in non-GCB DLBCL. The Examiner relied on secondary reference to render the use of this compound in patients with CD79B mutations. Wilson teaches a method of treating the instant cancer comprising administering a BTK inhibitor, ibrutinib. Wilson teaches that increased expression of CD79B allowed for more sensitivity to the BTK inhibitor, and teaches that the response rate was 55% and had significant tumor reductions, and patients with increased expression of CD79b responded more frequently to the BTK inhibitor.
Thus, the use of Compound 1 to treat patients with non-GCB DLBCL is already known in the art – whether or not the patient has a CD79B mutation. However, given the known fact that Compound 1 is a more selective BTK inhibitor than ibrutinib and given the fact that Wilson teaches CD79B mutations and administering a drug within the same class as Compound 1, one of skilled in the art could have pursued administering Compound 1 to patients with non-GCB DLBCL, which includes the subgroup of patients with CD79B mutations.
With regards to the unexpected superior results and reasonable expectation of success, the Examiner refers Applicant to MPEP 716.02(c) and (d).
In this instant case, the use of Compound 1 (whether it’s alone or in combination with an anti-CD20 antibody) is known in the art to treat non-GCB DLBCL as taught by Wang above. With regards to the CD79B mutation, the Examiner relied on the reference of Wlison to remedy this deficiency. Wilson specifically teaches that increased expression of CD79B mutation indicates that the patient will be sensitive to BTK inhibitor treatment. Wilson specifically teaches that the response rate was 55% and significant tumor reductions, and patients with increased expression of CD79b responded more frequently to the BTK inhibitor. [pg 3, third paragraph] Thus, Applicant’s argued results that are known in the art, (1) use of Compound 1 (a BTK inhibitor) for the treatment of non-GCB DLBCL and (2) that CD79b mutations resulted in increased response of BTK inhibitors. Contrary to arguments, the “unexpected results” are expected based on the disclosure of the cited combined references.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
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/SARAH A ALSOMAIRY/Examiner, Art Unit 1646
/Zachariah Lucas/Supervisory Patent Examiner, Art Unit 1600
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