DETAILED ACTION
Claims 1-14, submitted on March 20, 2024, are pending in the application and are rejected for the reasons set forth below. No claim is allowed.
Notice of Pre-AIA or AIA Status
This application, filed on or after March 16, 2013, is being examined under the first-to-file provisions of the Leahy-Smith America Invents Act (AIA ), Pub. L. No. 112-29, 125 Stat. 284 (2011). In the event that 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 statu-tory 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.
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.
Claims 1-14 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particu-larly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
In claim 1, “the solid tumor” lacks antecedent basis.
In claim 10, “sensitive” is a term of degree that would be a matter of opinion. See MPEP 2173.05(b) (relative terminology). Furthermore, it is the examiner’s impression that every human has at least some sensitivity to bleeding. It may be a de minimis sensitivity, but the claims are indefinite because it is unclear which humans are sensitive and which are not.
Claims 2-9 and 11-14 are included in this rejection only inasmuch as they depend from the claims at issue.
Claim Rejections – 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 4-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Byrd et al., N. Engl. J. Med. 2013;369(1):32-42.
Byrd discloses (see Abstract) a method of treating chronic lymphocytic leukemia in a human comprising administering 420 mg or 840 mg of ibrutinib,1 which is the first compound recited in instant claim 4. Note that instant claim 1 mentions that “the dose is effective to inhibit signaling between a cell of [a] solid tumor cancer at least one microenvironment,” but it does not specifically require that the human actually has a solid tumor, only that the dosage amount is sufficient to produce certain effects. The doses taught by the reference, i.e., 420 mg or 840 mg, is within the “dose” defined in applicant’s specification (p. 87, para. 00288), so claims 1 and 4-5 are anticipated.
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.
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.
Claims 1-2, 5, and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2013/010868 A1 by Barf et al.
Barf discloses (see Example 6 at pp. 35-36) the first BTK inhibitor illustrated in claim 2, which is commonly known as acalabrutinib.2 This compound is useful in treating human cancers that are mediated by Bruton’s Tyrosine Kinase (BTK) (p. 1, ll. 6-9). Barf further discloses that “a dosage for humans preferably contains 0.0001-25 mg per kg body weight” (p. 20, ll. 24-25), which overlaps with the “dose” referred to in instant claim 1 and as further defined in applicant’s own specification (p. 87). As explained above, instant claim 1 mentions that “the dose is effective to inhibit signaling between a cell of [a] solid tumor cancer at least one microenvironment,” but it does not specifically require that the human actually has a solid tumor, only that the dosage amount is sufficient to produce certain effects. The doses taught by the reference (p. 20, ll. 24-25) substantially overlap with the doses explained in applicant’s specification (p. 87), so a prima facie case of obviousness exists. See MPEP 2144.05(I) (“In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.”). Barf also discloses treating B cell lymphomas (p. 21, ll. 7-20), such as chronic lymphocytic leukemia (p. 22, l. 17), which meets the limitations of claim 5. Claims 10-11 are included in this rejection because, as explained above, every human, including the humans suggested by the reference, have at least some risk of bleeding events.
Claims 1-3, 5, and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Barf (WO 2013/010868 A1) as applied to claims 1-2, 5, and 10-11 above, and further in view of Byrd et al., J. Clin. Oncol. 2001;19(8):2153-64.
The disclosure of Barf is relied upon as set forth above. In addition, note that Barf acknowledges combination therapy with other drugs (p. 19, l. 29). The difference between the prior art and the claims at issue is that Barf does not specifically disclose combination therapy with an anti-CD20 antibody, such as rituximab. Byrd, however, discloses that rituximab was known in the prior art as being useful in the treatment of chronic lymphocytic leukemia. As a matter of law, it is prima facie obvious to combine two therapies, each of which is taught by the prior art to be useful for the same purpose, in order to form a combination therapy to be used for the very same purpose. The idea of combining them “flows logically from their having been individually taught in the prior art.” See MPEP 2144.06(I) (combining equivalents known for the same purpose). The cited references are evidence that acalabrutinib (Barf) was known to be useful in treating chronic lymphocytic leukemia and that rituximab (Byrd) was also known in the prior art to be useful in treating the very same disease. Their combined use within the meaning of instant claim 3 is therefore prima facie obvious.
Claims 1, 6, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over either Byrd as applied to claims 1 and 4-5 above, or Barf as applied to claims 1-2, 5, and 10-11 above, and further in view of Eifert et al., Genes Chromosomes Cancer 2013;52(10):961-75.
The disclosures of Byrd and Barf are relied upon as set forth above. The difference between the prior art and the claims at issue is that neither of these two references specifically discloses treating a solid tumor, such as breast cancer. Eifert, however, discloses that aberrant BTK is expressed at significantly higher levels in tumorigenic breast cells than in normal breast cells.” Apprised of the utility of ibrutinib (Byrd) or acalabrutinib (Barf) as BTK inhibitors, it would have been apparent that they would also be useful in the treatment of BTK-mediated breast cancer within the meaning of instant claim 6 and 14.
Claims 1, 6-9, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Byrd or Barf in view of Eifert as applied to claims 1, 6, and 14 above, and further in view of Roy et al., Ann. Oncol. 2009;20(3):449-53.
The disclosures of Byrd, Barf, and Eifert are relied upon as set forth above. The difference between the prior art and the claims at issue is that none of these references specifically discloses combination therapy with gemcitabine or albumin-bound paclitaxel. Both of these treatments, however, were known in the prior art, for example, as taught by Roy, as being useful for the treatment of breast cancer. The combination of ibrutinib (Byrd) or acalabrutinib (Barf) in the treatment of breast cancer (Eifert) with gemcitabine or albumin-bound paclitaxel (Roy) would have been prima facie obvious for the reasons discussed in MPEP 2144.06(I) (combining equiva-lents known for the same purpose). As explained above, dosage amounts taught by the refer-ences are consistent with the “dose” defined in applicant’s own specification (p. 87), so the examiner concludes that the subject matter of instant claim 9 is prima facie obvious.
Claim Rejections – 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 12-13 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention.
The claims at issue are directed to a method of “treating a cancer in a human sensitive to bleeding events” (see claim 10) comprising “administering … an anticoagulant or an antiplatelet active pharmaceutical ingredient” (claims 12-13). The prior art, however, indicates that this is the opposite of accepted medical practice. For example, Levine et al., Chest 2001;119(1 Suppl):108S-121S discloses that “[t]he major complication of anticoagulant therapy is bleeding” and “[t]here is a strong relationship between the intensity of anticoagulant therapy and the risk of bleeding” (p. 108S). Similarly, Melkonian et al., J. Thromb. Haemost. 2017;15(7):1500-10 discloses that “treatment with antiplatelet drugs in [elderly] patients should be carefully weighed against the risk” and antiplatelet drugs “carry a risk of major bleeding that appears to be equal or very close to that of oral anticoagulants” (p. 1508). Additionally, Shoeb et al., Thromb. Throm-bolysis 2013;35(3):312-19 discloses that “[a]nticoagulant medications are … associated with significant bleeding risks” and “[d]espite the high efficacy of oral anticoagulation, concerns about their related hemorrhagic complications prevent many patients from being prescribed or main-tained on therapy” (p. 312). For someone at risk of hemorrhage, one would understand the prior art as urging that anticoagulants and antiplatelet agents be avoided. One would also view inten-tionally administering them in the manner recited in claims 12-13 as being inconsistent with sound medical judgment.
One of skill in the art would therefore be skeptical of the premise of applicant’s invention and would look to the specification for information about how it is performed in actual clinical practice. The specification explains that “bleeding has been reported in up to 50% of ibrutinib-treated patients” (see Example 4 at p. 131). Applicant also presents data about the effects of BTK inhibitors on thrombus formation (pp. 131-34). Nowhere, however, does applicant posit a rationale for why an anticoagulant or antiplatelet agent would be useful in “a human sensitive to bleeding events” as required by the instant claims. Given the lack of working examples in appli-cant’s specification, and the explicit teaching in the prior art against administration of an antico-agulant or antiplatelet agent in a person at risk of bleeding, the examiner concludes that one of skill in the art would be burdened with undue experimentation when attempting to practice the invention as claimed.
Claims 1-4 and 6-14 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for the subject matter of claim 5, does not reasonably provide enablement for the treatment of all cancers within the scope of the independent claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The focus of the examination inquiry is whether everything within the scope of the claim is enabled. Accordingly, the first analytical step requires that the examiner determine exactly what subject matter is encompassed by the claims. The specification must teach those skilled in the art how to make and use the full scope of the claimed invention without “undue experimen-tation” or that any experimentation must be “reasonable.” The scope of enablement must bear a “reasonable correlation” to the scope of the claims, although the more one claims, the more one must enable. With respect to the breadth of a claim, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate with the scope of protection sought by the claims. See MPEP 2164.08 (enablement commensurate in scope with the claims).
The claims at issue are drawn to treatment of any type of cancer with a BTK inhibitor. As applicant’s own specification explains, “Bruton’s Tyrosine Kinase (BTK) is a Tec family non-recep-tor protein kinase expressed in B cells and myeloid cells” and “BTK is expressed in numerous B cell lymphomas and leukemias” (p. 1). Byrd, discussed above, discloses using a BTK inhibitor in a method of treating chronic lymphocytic leukemia. Barf, also discussed above, discloses using a BTK inhibitor in a method of treating human cancers that are mediated by Bruton’s Tyrosine Kinase (BTK). It is implicit that one of skill in the art is a person who can read and understand these references, as well as applicant’s own specification. The examiner acknowledges that the use of BTK inhibitors in the treatment of BTK-mediated cancers is known in the art, but the prior art search reveals that the use of these drugs in the treatment of the full scope of cancers embraced by the claims would not be credible. Applicant’s own specification does not posit any rational explanation, and there are no working examples to support such a hypothesis, whereby one would reasonably expect these BTK inhibitors to be useful in treating the full range of cancers within the scope of claims 1-4 and 6-14. The examiner therefore concludes that one of skill in the art would be burdened with undue experimentation when attempting to practice the treat-ment methods as claimed.
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 possi-ble 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 provi-sions 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 accompa-nied 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 1-2, 5 and 10-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 9,718,828 B2. Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the ‘828 Patent are directed to acalabrutinib and related compounds. The specification of the ‘828 Patent (col. 55, ll. 20-30) explains that these compounds are useful for treating a variety of lymphomas within the meaning of instant claim 5. As explained above, everyone has at least some risk of bleeding, so the examiner concludes that the treatment claimed in the ‘828 Patent also meets the limitations of instant claims 10-11.
Claims 1-6 and 10-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 9,949,971 B2. Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘971 Patent claims a method of a method of treating a hyperproliferative disease (see claim 1) comprising adminis-tering compounds within the scope of instant claims 2 and 4 (see claims 2-3 of the ‘971 patent). Dependent claim 5 of the ‘971 Patent is directed to a method further comprising administering a therapeutically effective amount of an anti-CD20 antibody, such as rituximab. Dependent claims 9-10 of the ‘971 Patent are directed to treating lymphomas and solid tumors within the scope of instant claims 5-6.
Claims 1-3, 5, and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,272,083 B2. Although the claims at issue are not identical, they are not patentably distinct from each other. The ‘083 Patent claims a method of treating chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) in a human subject suffering therefrom, comprising the step of orally administering, to the human subject, the first compound recited in instant claim 2. Dependent claims 5-7 of the ‘083 Patent meet the limitations of instant claims 3 and 12-13, respectively.
Claims 1-3, 5, and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,090,302 B2. Although the claims at issue are not identical, they are not patentably distinct from each other for substantially the same reasons discussed above.
Claims 1-3, 5, and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,771,696 B2 for substantially the same reasons discussed above.
Claims 1-3, 5, and 10-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,263,164 B2 for substantially the same reasons discussed above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Theodore R. Howell whose telephone number is (571)270-5993. The exam-iner can normally be reached Monday - Thursday, 8:00 am - 7:00 pm (Eastern Time). Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interview practice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached at (571)272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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THEODORE R. HOWELL
Primary Examiner
Art Unit 1628
/THEODORE R. HOWELL/ Primary Examiner, Art Unit 1628
January 7, 2026 (revised January 22, 2026)
1 CAS Reg. No. 936563-96-1.
2 CAS Reg. No. 1420477-60-6.