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
Election of Species and Status of the Claims
Applicant’s election of ‘cerdulatinib’ as the kinase inhibitor, and ‘a patient who has decreased frequency of naïve B cells within total B cells, and has increased frequency of memory switched B cells or double negative B cells within total B cells,’ as the patient population in the response filed on November 5th 2025 is acknowledged. Claims 1-22 are pending. Claims 2-5, 11-18, and 21 are withdrawn from further consideration as being directed towards nonelected species until a generic claim has been found allowable. Note: Claims 2-5 and 11-17 each further limit the patient population to include particular aspects not recited in the elected species of ‘a patient who has decreased frequency of naïve B cells within total B cells, and has increased frequency of memory switched B cells or double negative B cells within total B cells.’ Note the description of the patient-population species election in the election of species requirement filed on September 10th 2025. Claim 18 is directed to species of PI3K inhibitors, which does not include applicant’s elected kinase inhibitor of cerdulatinib. Claims 1, 6-10, 19-20, and 22 are examined on their merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statement filed on November 5th 2025 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
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 1, 6-10, 19-20, and 22 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.
Claims 1, 9, 10 and their dependent claims 6-8, 19-20, and 22 are indefinite for the phrase, “wherein the increase and decrease are as compared to a corresponding healthy subject not having the B cell lymphoma,” because one of ordinary skill in the art could not reasonably determine the metes and bounds of the claims from the claim language. Specifically, no standardized range is recited for each of the described biomarkers in a healthy subject. One of ordinary skill in the art would thereby be unable to determine what constitutes an increase or decrease in each of the biomarker levels as compared to a healthy subject. For example, see Figure 6, which applicant describes as “demonstrating that separation of Group 3 is mainly driven by over-representation of switched memory and double negative B cells, corresponding with loss of naïve B cells.” However, a portion of the patient population in each measurement of ‘Group 3’ patients has lower double negative/ memory switched cells and/or higher naïve B cells as compared to a “healthy control.” Thus, by applicant’s own definition, they would be excluded from the criteria of treatment. Additionally, The variance in these biomarkers for the “healthy control,” necessarily results in classification of “healthy subjects” within the “treatment population.” See Figure 6:
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As demonstrated in applicant’s Figure 6, the variance in percent-switched-memory B cells is as much as 100% in applicant’s “healthy control” population (with a maximum value of approximately 25% and a minimum value of approximately 10%). Applicant’s definition of what constitutes an “increase” or “decrease in “frequency of switched memory B cells” is found in paragraph [0039]:
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Thus, by applicant’s own definition, a consequential proportion of the “healthy control” population would be defined as having an increase or decrease in these biomarkers as compared to a “healthy” patient population. As no standardized range for any of the defined biomarkers is presented, one of ordinary skill in the art could not reasonably determine the scope of the patient population described in the claims, claims 1, 9, 10 and their dependent claims 6-8, 19-20, and 22 are indefinite.
Claims 9 and 10, as well as their dependent claims 11-14 are indefinite for the phrase “wherein the patient is identified as suitable for treatment if the patient has decreased frequency of naïve B cells within total B cells, and has increased frequency of memory switched B cells or double negative B cells within total B cells.” The claims each describe the selection of a patient for treatment comprising a two-step process of first determining three biomarkers from a blood sample, followed by selecting a patient based on said biomarkers.
The three biomarkers described are:
The number of total B cells
The number of transitional B cells
The number of naïve B cells
The following patient selection process is then dependent on five biomarkers as determined by the preceding blood sample:
The number of total B cells
The number of transitional B cells
The number of naïve B cells
The number of memory switched B cells
The number of double negative B cells
The number of memory switched B cells in the patient’s blood sample is never determined in the preceding blood sample. The limitations of patient selection based on memory switched or double negative B cells therefore lack antecedent basis and claims 9 and 10 are indefinite.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 9, 10 and their dependent claims 6-8, 19-20, and 22 rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claims recite the administering of a kinase inhibitor only if the patient receiving the administration exhibits a particular naturally occurring correlation (i.e. a specific distribution of circulating B cell subpopulations). This judicial exception is not integrated into a practical application because each of these subset frequencies arise naturally in the body of the patient, dependent on the patient’s disease state and immune physiology, but completely independent of human activity. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional elements of the claim beyond the mere observation and recording of the natural phenomena are considered routine1. See MPEP 2106.05(g):
Another consideration when determining whether a claim integrates the judicial exception into a practical application in Step 2A Prong Two or recites significantly more in Step 2B is whether the additional elements add more than insignificant extra-solution activity to the judicial exception. The term "extra-solution activity" can be understood as activities incidental to the primary process or product that are merely a nominal or tangential addition to the claim. Extra-solution activity includes both pre-solution and post-solution activity. An example of pre-solution activity is a step of gathering data for use in a claimed process.
As explained by the Supreme Court, the addition of insignificant extra-solution activity does not amount to an inventive concept, particularly when the activity is well-understood or conventional.
See also Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 79, 101 USPQ2d 1961, 1968 (2012) (additional element of measuring metabolites of a drug administered to a patient was insignificant extra-solution activity).
Below are examples of activities that the courts have found to be insignificant extra-solution activity:
Mere Data Gathering:
vi. Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis).
Applicant’s claims thus amount to a two-step combination of
Observing/measuring naturally occurring B-cell subset frequencies (i.e. regarded as routine observation)
Applying a well-known, conventional treatment option if a particular natural correlation is present.
See Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66 (2012):
the relationships between concentrations of certain metabolites in the blood and the likelihood that a thiopurine drug dosage will prove ineffective or cause harm—are not themselves patentable, the claimed processes are not patentable unless they have additional features that provide practical assurance that the processes are genuine applications of those laws rather than drafting efforts designed to monopolize the correlations. The three additional steps in the claimed processes here are not themselves natural laws but neither are they sufficient to transform the nature of the claims. The “administering” step simply identifies a group of people who will be interested in the correlations, namely, doctors who used thiopurine drugs to treat patients suffering from autoimmune disorders. Doctors had been using these drugs for this purpose long before these patents existed. And a “prohibition against patenting abstract ideas ‘cannot be circumvented by attempting to limit the use of the formula to a particular technological environment.’ ” Bilski, supra, at ___. The “wherein” clauses simply tell a doctor about the relevant natural laws, adding, at most, a suggestion that they should consider the test results when making their treatment decisions. The “determining” step tells a doctor to measure patients’ metabolite levels, through whatever process the doctor wishes to use. Because methods for making such determinations were well known in the art, this step simply tells doctors to engage in well-understood, routine, conventional activity previously engaged in by scientists in the field. Such activity is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law. Parker v. Flook, 437 U.S. 584, 590. Finally, considering the three steps as an ordered combination adds nothing to the laws of nature that is not already present when the steps are considered separately. Pp. 8–11.
As applicant’s claims are directed towards a routine treatment further limited only by the determination of a particular naturally occurring correlation2, the claims are directed towards a natural phenomenon and are thereby deemed ineligible subject matter.
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.
Claims 1, 6-9, 19-20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Ma (Ma et al., Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma. Oncotarget. 2015 Dec 22;6(41):43881-96)).
Claim 1 is directed towards the treatment of a B cell lymphoma comprising administration of a kinase inhibitor wherein the patient:
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Ma teaches the treatment of diffuse large B-cell lymphoma (DLBCL) via administration of the combination Syk/JAK kinase inhibitor, cerdulatinib (Ma, pg. 43884). While Ma does not explicitly further limit the patient population to one that carries the specified biomarkers at a higher/lower frequency than that of a healthy subject, it is unclear how this limitation further limits the patient population described in claim 1 (see the above 112(b) rejection for claim 1). Furthermore, as described in the above 101 rejection for claim 1, the described biomarker determination does not meaningfully limit the patient population (i.e. narrowing of a patient population to a subpopulation is obvious absent evidence of unexpected results, critically in said subpopulation, or wherein the broader patient population is taught away). As one of ordinary skill in the art would reasonably treat the patient population described in claim 1 with cerdulatinib, claim 1 is prima facie obvious.
Claims 6-8 further limit the method of claim 1 to:
wherein the frequencies are determined in a blood sample obtained or derived from the patient (claim 6)
wherein the method further comprises obtaining a blood sample and determining B cell numbers (claim 7)
wherein the described transitional B-cells comprise CD10+ transitional B cells, or CD38+ transitional B cells, or both (claim 8)
In each of the three cases, only the additional steps of measuring a naturally occurring correlation are limited, and the method of treatment itself is not. Thus, claims 6-8 are prima facie obvious over Ma for the same reasons as claim 1.
Claim 9 is directed towards a method for treating a B cell lymphoma, comprising:
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As stated in the above rejections, absent unexpected results the limiting of the patient population as described in the first and second portions of the claim are obvious variations of a known method. As Ma teaches the treatment of diffuse large B-cell lymphoma (DLBCL) via administration of the combination Syk/JAK kinase inhibitor, cerdulatinib (Ma, pg. 43884), claim 9 is prima facie obvious.
Claims 19-20 and 22 limit the kinase inhibitor in claim 1 to cerdulatinib and are prima facie obvious for the same reasons as claim 1.
Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 6-9, 19-20, and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3-6 of U.S. Patent No. 11,446,300. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent teaches the treatment of B-cell lymphomas including CLL, DLBCL, and SLL via administration of cerdulatinib. As described in the above rejections, absent unexpected results the limiting of the patient population as described in claims 1 and 9 are obvious variations of a known method. Thus, the instant claims are obvious over those of U.S. Patent No. 11,446,300.
Claims 1, 6-9, 19-20, and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-8 of U.S. Patent No. 10,736,895. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent teaches the treatment of B-cell lymphomas including CLL, DLBCL, and SLL via administration of cerdulatinib. As described in the above rejections, absent unexpected results the limiting of the patient population as described in claims 1 and 9 are obvious variations of a known method. Thus, the instant claims are obvious over those of U.S. Patent No. 10,736,895.
Claims 1, 6-9, 19-20, and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,350,269. Although the claims at issue are not identical, they are not patentably distinct from each other because the reference patent teaches the treatment of follicular lymphoma (a B-cell lymphoma) via administration of cerdulatinib. As described in the above rejections, absent unexpected results the limiting of the patient population as described in claims 1 and 9 are obvious variations of a known method. Thus, the instant claims are obvious over those of U.S. Patent No. 12,350,269.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Anthony Seitz whose telephone number is (703)756-4657. The examiner can normally be reached 7:30 AM ET - 5:00 PM ET M-F.
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/A.J.S./Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 See Ma (Ma et al., Cerdulatinib, a novel dual SYK/JAK kinase inhibitor, has broad anti-tumor activity in both ABC and GCB types of diffuse large B cell lymphoma. Oncotarget. 2015 Dec 22;6(41):43881-96) who describes the administration of the dual Syk/JAK inhibitor, cerdulatinib, for the treatment of diffuse large B-cell lymphoma.
2 Note that claim 10 does not include a treatment step, but only the determination of said natural correlation.