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
This action is in response to papers filed March 23, 2026. Applicant’s reply to the restriction/election requirement of February 26, 2026 has been entered. Claims 21-30 have been canceled. Claims 1-20 are pending in the application.
Priority
Applicant’s claim for the benefit as a continuation of prior-filed U.S. Patent Application No. 18/206,290, filed June 6, 2023, which claims the benefit as a continuation of prior-filed U.S. Patent Application No. 18/098,938, filed January 19, 2023, which claims the benefit of prior-filed U.S. Provisional Patent Application Nos. 63/366,053, 63/383,504, 63/383,503, 63/384,864, and 63/387,796, filed June 8, 2022, November 13, 2022, November 13, 2022, November 23, 2022, and December 16, 2022, respectively, under 35 U.S.C. 119(e), is acknowledged.
Election/Restrictions
Applicant’s election without traverse of Group III, claims 11-19, is acknowledged. Applicant’s elections of i) “CLL” as the species of patient disease, ii) “320 mg once a day” as the species of Zanubrutinib dosage, iii) “evidence of marrow failure” as the species of criterion for requiring treatment of CLL or SLL, iv) “fatigue” as the species of constitutional symptom, v) “myocardial infarction within 6 months” as the species of manifestation of clinically significant cardiovascular disease, v) “treatment with monoclonal antibody-based therapy within 28 days prior” as the species of prior treatment, and vi) “patient that has relapsed CLL” as the species of further patient characteristic are all also acknowledged. The Examiner has determined that claims 11-16 and 19 read on the elected subject matter.
Accordingly, claims 1-10, 17, 18, and 20 are hereby withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter, there being no allowable generic or linking claim.
Election was made without traverse in the reply filed on March 23, 2026. Claims 11-16 and 19 are under examination.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 11-16 and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 11 is directed to “a method of prolonging progression-free survival (PFS) time compared to administering ibrutinib at a dose of 420 mg once daily”, then discloses that the patient has CLL or SLL, then stipulates “in need thereof”, and recites administering Zanubrutinib at the stipulated doses, either 160 mg twice a day or 320 mg once a day; which renders the claim indefinite for the following reasons:
1. One of ordinary skill in the art cannot make heads or tails out of the claimed subject matter. Indeed, one of ordinary skill in the art would be quite familiar with treating CLL or SLL with zanubrutinib at the recited doses, e.g. 320 mg once a day. One of ordinary skill in the art, though, would not understand what this has to do with 420 mg of ibrutinib. For example, does the method require first actively administering 420 mg ibrutinib to the patient, and then administering the Zanubrutinib? Or rather is this just a botched attempt to simply re-patent the known method of treating CLL or SLL with Zanubrutinib at the stipulated doses? Or is Applicant merely trying to patent the comparative data for the PFS time prolongation between ibrutinib and Zanubrutinib?
2. While the claim establishes that the patient has CLL or SLL, the claim then stipulates that the patient is “in need thereof”. One of ordinary skill in the art cannot definitively ascertain the metes and bounds of “in need thereof”. For example, is the patient one who has been treated with ibrutinib but has not achieved an adequate PFS time, so is in need of a greater PFS time? Is the patient one who is trying to decide between taking ibrutinib and Zanubrutinib but has decided that they are in need of the Zanubrutinib? Or what?
***For examination at this time, the claim is being interpreted as simply a method of treating CLL or SLL by administering Zanubrutinib at the recited dose. Including the statement comparing the relative PFS time data between ibrutinib and Zanubrutinib is being interpreted as merely an attempt to re-patent this known method, but which has no bearing on the patentability of the claimed method.
Claim 12, which depends from claim 11, stipulates that the patient has “measurable disease” by CT or MRI. Claim 11 already establishes that the patient has CLL or SLL. One of ordinary skill in the art thus cannot definitively ascertain the metes and bounds of “measurable disease”. For example, is “measurable disease” simply the CLL or the SLL? Or is “measurable disease” another disease beyond the CLL and SLL? Or what?
Claim 13, which depends from claim 12, and ultimately claim 11, stipulates that the patient “requires treatment of CLL or SLL as manifested by at least one of” the recited criteria. Claim 11 already provides that the patient has CLL and SLL, which are known diseases that require treatment, and one of ordinary skill in the art would understand that by administering Zanubrutinib at the recited dose the CLL or SLL is being treated. One of ordinary skill in the art cannot definitively ascertain how these criteria further limit the actual method of claim 11. Whether the patient meets any one of the specific criteria listed they are still being treated for CLL or SLL by being administered Zanubrutinib at the recited doses. Whether the patient meets the criteria or not they are being treated according to claim 11.
Claim 13 stipulates that the patient has “a life expectancy of at least 6 months”. This is an arbitrary and subjective criterion, i.e. guessing. It’s simply an arbitrary prediction that one cannot know for sure. One of ordinary skill in the art thus cannot definitively ascertain whether the patient will live for at least 6 more months or not.
Claim 13 stipulates that the patient has “a serum total bilirubin of more than 2.0 times of upper limit of the normal range”. This appears to be another disease that would not only require treatment beyond the Zanubrutinib, but, as one of ordinary skill in the art would recognize, is also a feature for which treatment with Zanubrutinib is contraindicated. One of ordinary skill in the art thus cannot definitively ascertain the metes and bounds of the claimed subject matter.
***This appears to be a typo since the original specification discloses that the bilirubin should be no more than 2 times the upper limit.
Claim 13 stipulates that the patient should be “practicing contraception”. One of ordinary skill in the art cannot definitively ascertain whether claim 13 limits the patient to female only.
Claim 14 stipulates that the patient does not have prior treatment with “a BTK inhibitor”. The acronym “BTK” is not defined by the claim. Claims must stand alone to define the invention, and should not rely on the specification or extraneous materials to give them meaning. Applicant is advised to first recite the proper name and then the acronym can be employed.
Claim 14 stipulates that the patient does not have “major surgery within 4 weeks of the first dose of study drug”, which renders the claim indefinite for the following reasons:
1. First, one of ordinary skill in the art cannot definitively ascertain the metes and bounds of “major surgery”, and what surgery is major and what surgery is not major.
2. Claim 14 depends ultimately from claim 11. One of ordinary skill in the art cannot make heads or tails out of “the first dose of study drug”. Claim 11 mentions two drugs, ibrutinib and Zanubrutinib. One of ordinary skill in the art cannot definitively ascertain whether “study drug” is ibrutinib, Zanubrutinib, or something else entirely.
Claim 15 stipulates that the patient does not have “known prolymphocytic leukemia” or “currently suspected Richter’s transformation”. This appears to be arbitrary, subjective, and hypothetical. One of ordinary skill in the art cannot definitively ascertain whether the patient actually has prolymphocytic leukemia or Richter’s transformation.
Claim 15 recites “New York Heart Association class III or IV congestive heart failure”, which is not defined by the claim. Claims must stand alone to define the invention, and should not rely on the specification or extraneous materials to give them meaning.
Claim 15 recites “QTcF…based on Fridericia’s formula, which is not defined bv the claim. Claims must stand alone to define the invention, and should not rely on the specification or extraneous materials to give them meaning.
Claim 15 recites “severe or debilitating pulmonary disease”. This is an arbitrary, relative, and subjective criterion not defined by the claim. One of ordinary skill in the art cannot definitively ascertain the metes and bounds of the claimed subject matter, and what pulmonary disease is “severe” and which pulmonary disease is not severe.
Claim 15 recites that the patient does not have “known CNS involvement by leukenia or lymphoma” or “known infection with HIV”. One of ordinary skill in the art thus cannot definitively ascertain whether the patient actually does not have CNS involvement by leukemia or lymphoma, and whether or not the patient actually does not have HIV infection.
Claim 15 recites the acronym “ANC”, which is not defined by the claim. Claims must stand alone to define the invention, and should not rely on the specification or extraneous materials to give them meaning.
Claims 12-16 and 19 are (also) indefinite for depending from an indefinite claim.
Claim Rejections - 35 USC § 103 (I and II)
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
I. Claims 11, 12, 14-16, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (Abstract; 2019).
I. Applicant Claims
Applicant’s elected subject matter is directed to a method of treating relapsed CLL in a patient in need thereof comprising orally administering to the patient 320 mg Zanubrutinib once a day; wherein the patient is 18 years of age or older, and wherein the progression-free survival (PFS) time is prolonged compared to administering ibrutinib at a dose of 420 mg once daily.
I. Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Xu et al. disclose a method of treating relapsed CLL in a patient in need thereof comprising orally administering to the patient 320 mg Zanubrutinib once a day; wherein the patient is 18 years of age or older, and wherein the progression-free survival (PFS) time is prolonged as a result of the treatment.
I. Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Xu et al. do not explicitly anticipate the presently claimed subject matter under 35 USC 102, since Xu et al. do not disclose the comparison between the PFS for e.g. 320 mg once daily Zanubrutinib and 420 mg once daily for ibrutinib, and do not explicitly address the conditions that the patient cannot have as recited in claims 14 and 15. However, the Xu et al. disclosure is sufficient to render the presently claimed subject matter prima facie obvious within the meaning of 35 USC 103.
I. Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to employ the teachings of Xu et al., outlined supra, to devise Applicant’s presently claimed method.
Xu et al. disclose a method of treating relapsed CLL in a patient in need thereof comprising orally administering to the patient 320 mg Zanubrutinib once a day; wherein the patient is 18 years of age or older, and wherein the progression-free survival (PFS) time is prolonged as a result of the treatment.
Since Xu et al. disclose treating the same disease, i.e. relapsed CLL, with the very same active method step, i.e. orally administering Zanubrutinib at 320 mg once daily, and to the same type of patient, i.e. adults 18 years of age and older, the outcome must be the same as well, including the result of prolonging the progression-free survival (PFS) time compared to administering ibrutinib at a dose of 420 mg once daily.
Moreover, the patients being treated by Xu et al. do not necessarily have any of the conditions recited in claims 14 and 15. Moreover, in view of the nature of the disease being treated, i.e. CLL, and also in view of the common treatment related adverse events reported by Xu et al., it would certainly be well within the skill of the ordinary mechanic in the art, e.g. any competent doctor or nurse, to exclude patients that would be at particular risk for treatment with Zanubrutinib.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
II. Claims 11-16, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (Abstract; 2019), in view of Anonymous (BeiGene, Ltd. [online]; 2019).
II. Applicant Claims
Applicant’s elected subject matter is directed to a method of treating relapsed CLL in a patient in need thereof comprising orally administering to the patient 320 mg Zanubrutinib once a day; wherein the patient requires treatment for CLL, is 18 years of age or older, has an ECOG status of 0-2, has a life expectancy of at least 6 months, has adequate bone marrow function (i.e. neutrophil count of at least 1000/mm3, platelet count of at least 75,000/mm3), has adequate organ function (e.g. creatinine clearance of at least 30 mL/min), and is practicing contraception; and wherein the progression-free survival (PFS) time is prolonged compared to administering ibrutinib at a dose of 420 mg once daily.
II. Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Xu et al. disclose a method of treating relapsed CLL in a patient in need thereof comprising orally administering to the patient 320 mg Zanubrutinib once a day; wherein the patient obviously requires treatment for CLL, is 18 years of age or older, has an ECOG of 0-1, and has sufficient organ function; and wherein the progression-free survival (PFS) time is prolonged as a result of the treatment.
BeiGene discloses that patients receiving e.g. 320 mg Zanubrutinib once a day were 34-86 years of age, had an ECOG status of 0-1, had a median of 2 prior lines of therapy, required a neutrophil count of ≥ 1 x 109/L, a platelet count of ≥ 75 x 109/L, a creatinine clearance of ≥ 30 mL/min, hepatic enzymes ≤ 2.5 x upper limit of normal, and bilirubin ≤ 1.5 x ULN; that a large majority of patients continue Zanubrutinib treatment for 6 months or longer; and that female patients should use effective contraception during treatment since Zanubrutinib can cause embryo-fetal harm.
II. Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Xu et al. do not explicitly disclose that the patient has a life expectancy of at least 6 months, has a neutrophil count of at least 1000/mm3, a platelet count of at least 75,000/mm3, a creatinine clearance of at least 30 mL/min, and is practicing contraception. These deficiencies are cured by the teachings of BeiGene.
II. Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to combine the respective teachings of Xu et al. and BeiGene, outlined supra, to devise Applicant’s presently claimed method.
Xu et al. disclose a method of treating relapsed CLL in a patient in need thereof comprising orally administering to the patient 320 mg Zanubrutinib once a day; wherein the patient requires treatment of CLL, is 18 years of age or older, has an ECOG of 0-1, and has sufficient organ function; and wherein the progression-free survival (PFS) time is prolonged as a result of the treatment. Since BeiGene disclose that patients being treated with e.g. 320 mg Zanubrutinib once a day were 34-86 years of age, had an ECOG status of 0-1, had a median of 2 prior lines of therapy, required a neutrophil count of ≥ 1 x 109/L, a platelet count of ≥ 75 x 109/L, a creatinine clearance of ≥ 30 mL/min, hepatic enzymes ≤ 2.5 x upper limit of normal, and bilirubin ≤ 1.5 x ULN; that a large majority of patients continue Zanubrutinib treatment for 6 months or longer; and that female patients should use effective contraception during treatment since Zanubrutinib can cause embryo-fetal harm; one of ordinary skill in the art would thus be motivated to treat patients for CLL with 320 mg Zanubrutinib once a day who are e.g. 34-86 years of age, have an ECOG status of 0-1, have a median of 2 prior lines of therapy, have a neutrophil count of ≥ 1 x 109/L, have a platelet count of ≥ 75 x 109/L, have a creatinine clearance of ≥ 30 mL/min, have hepatic enzymes ≤ 2.5 x upper limit of normal, and have bilirubin ≤ 1.5 x ULN, and are on contraception, with the reasonable expectation that the resulting treatment of CLL will be successful with a minimum incidence and/or severity of adverse side effects.
Since Xu et al. disclose treating the same disease, i.e. relapsed CLL, with the very same active method step, i.e. orally administering Zanubrutinib at 320 mg once daily, and to the same type of patient, i.e. adults 18 years of age and older, the outcome must be the same as well, including the result of prolonging the progression-free survival (PFS) time compared to administering ibrutinib at a dose of 420 mg once daily.
Although BeiGene reports employing Zanubrutinib for treatment of mantle cell lymphoma (MCL), rather than CLL, both MCL and CLL are B-cell malignancies that arise from CD5+ B cells, and both diseases have similar symptoms. Moreover, the same compound, i.e. Zanubrutinib, is being administered in the same amount, e.g. 320 mg once a day, and produces the same adverse side effects in both sets of patients. Therefore, one of ordinary skill in the art would be motivated to employ patients for treatment of CLL that meet the same criteria as the patients for treatment of MCL, such as e.g. an ECOG status of 0-1, a neutrophil count of ≥ 1 x 109/L, a platelet count of ≥ 75 x 109/L, a creatinine clearance of ≥ 30 mL/min, hepatic enzymes ≤ 2.5 x upper limit of normal, bilirubin ≤ 1.5 x ULN, and practicing contraception for the most optimal outcome, i.e. successful treatment with minimal adverse side effects.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID BROWE whose telephone number is (571)270-1320. The examiner can normally be reached Monday - Friday, 9:30 AM to 6 PM EST.
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/DAVID BROWE/Primary Examiner, Art Unit 1617
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