DETAILED ACTION
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 .
Priority
This application was filed on 05/15/2024 and claims priority of 63/502,209 filed on 05/15/2023; and is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/11/2024 was filed prior to the
mailing of the instant first Office action on the merits. The submission is in compliance with the
provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by
the examiner. A copy of Form PTO/SB/08 is attached to the instant Office action.
Claim Rejections - 35 USC § 102
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 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.
Claim(s) 1 and 4-13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yu et al (Discovery of a potent BTK and IKZF1/3 triple degrader through reversible covalent BTK PROTAC development. Curr Res Chem Biol. 2022; (2); doi: 10.1016/h.crcgvu.2022.100029).
Regarding claim 1, the prior art recites the compounds of claim 1, where the compounds are selected from PS-RC-1, PS-RC-2, PS-RC-3, PS-RC-4, PS-RC-Ctrl, PS-1, PS-2, PS-3, PS-4, PS-5, PS-6. Each of the compounds is expressly disclosed identical to claim 1 for structure and naming conventions (see Fig. 1, p.13).
Regarding claims 4-10 where a method of treating or preventing a BTK-related disease by administering an effective amount of the compound of claim 1 (as in instant claim 4-6), Yu et al discloses at the Abstract and throughout: “Building on our previous work on ibrutinib-based reversible covalent Bruton’s tyrosine kinase (BTK) PROTACs… we developed PS-2 as a potent BTK and IKZF1/3 triple degrader with high specificity.” Reference A further discloses testing in Mino cells (mantle cell lymphoma, MCL) and Ramos/A20 B-cell lymphoma cell lines (Figure 5), demonstrating anti-cancer activity. The application’s own specification (instant specification ¶3) identifies MCL and CLL as BTK-related cancers (as in reference art, Introduction, ¶1).
Regarding claims 11-13, Yu et al. expressly discloses methods of inducing BTK degradation in cells by treating the cells with compounds PS-2, PS-1, PS-3, and related compounds (as in claim 11). In the prior art, Figures 5-6 discloses contacting Mino, Ramos, and A20 cells with these compounds and quantifying BTK degradation by Western blot and BTK-Hibit knock-in assays. Claim 12 (in vitro) and claim 13 (in vivo) are both encompassed by the prior art’s cell-line experiments (p7, ¶2) and the mouse pharmacodynamic data where BTK degradation was detected in PBMC, spleen, and lymph nodes of PS-2-treated mice (p8, ¶2).
Claim 1 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Wang et al. (WO 2017/180417 A1).
Regarding claim 1 and 3, Wang et al. recites the compound of PS-6 (as in instant claim 1). Specifically, the compound is identified as the intermediate in Example 3, Step 5: Synthesis of S20 (pg. 617, ¶609) compound S20.
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Regarding claims 3, the prior art reads on a a kit (as instant claim 3). The prior art recites where the “Proper formulation is dependent upon the route of administration chosen.”. As disclosed where the therapeutically effective amount of the compound is orally administered as either a tablet, capsule, powder, etc., “…contain about 0.01% to about 95% and preferably from about 1% to about 50%, of a compound of the disclosure.” (¶492). Additionally, it is further noted where the administration can also include carriers such as water, petroleum or oils for liquid forms, and acceptable carriers for intravenous or subcutaneous (¶493) administrations. Wang et al. further discloses where kits comprise the compound of the disclosure packaged in a manner that facilitates use of the compound. Additional description of the kit includes a sealed bottle or vessel, with a label affixed to the container with described compound, dosage and administration (¶499). Wang et al. defines a therapeutically effective amount of the compound as “…to an amount of the active ingredient(s) that is(are) sufficient, when administered b a method of the disclosure, to efficaciously deliver the active ingredient(s) for the treatment of condition or other proliferation disorder…for the treatment of condition or disease of interest to an individual in need thereof.”. Additionally, Wang et al. discloses where the compounds of the disclosure presents where the administered amount is about .005 to about 500mg per dose. Regarding, the synthesis of Cod. No. 3 in Example 3 (¶601-609), Wand discloses the vessel of experimentation and the inclusion of a round-bottom flask, and the process to synthesize the intermediate of S20 of Cpd No. 3.
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.
Claim(s) 2-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al (Discovery of a potent BTK and IKZF1/3 triple degrader through reversible covalent BTK PROTAC development. Curr Res Chem Biol. 2022; (2); doi: 10.1016/h.crcgvu.2022.100029) as applied to claim 1 above, and further in view of Ansel (Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. 10th. Wolters Kluwer Health. 2013. Page 214-314).
Yu et al teaches within the introduction (p2, ¶2) the development of an orally available BTK degrader and later discloses (Discussion, p8, ¶1) the processes that the BTK PROTAC is formulated. Additionally, it is further disclosed where “…it would be ideal to develop BTK degraders as orally available agents from the translational point of view.” (p9, ¶3). However, Yu, does not specifically teach where a kit comprises compound 1.
Ansel teaches generally, the dosage forms pertaining to solid forms and drug delivery systems. The art specifically calls attention to the formulation of tablets, capsules, powder and granules and include examples of excipients (acceptable carriers) for the formulations. While Ansel does not specifically teach the use of “kit” as in the instant claim 3, Ansel does teach dosage packs and delivery methods for pre-measured dosages of medications for the delivery of single doses for the chosen administration route. As further disclosed, this can include individual or in combination drug powder mixtures as unit dose (p235, col2, ¶1), strip packaging for oral administration (p256, col2, ¶2) or similar forms.
Claim(s) 7-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yu et al (Discovery of a potent BTK and IKZF1/3 triple degrader through reversible covalent BTK PROTAC development. Curr Res Chem Biol. 2022; (2); doi: 10.1016/h.crcgvu.2022.100029) as applied to claim 1 above, and further in view of Cao et al. (The Immunomodulatory Functions of BTK Inhibition in the Central Nervous System; Journal of Inflammation Research; 11/24/2022; doi.org/10.2147/jir.s389958).
YU et al. teaches the use of BTK inhibitors (specifically ibrutinib) to be administered for the treatment of multiple forms of cancers to include mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). Specifically, the prior art references where BTK is “…present in all blood cell lines except for T cells and natural killer cells.” However, Yu et al does not teach where the BTK-related disease is a neurodegenerative disorder (as instant claim 7), an inflammatory disease (as instant claim 8) or includes a second agent (as instant claims 9-10).
Cao et al teaches where BTK inhibition simultaneously targets pathways that impact the neuroinflammation and neurodegenerative associated disorders (as instant claims 7-8). Specifically, testing was conducted in mouse models to identify the benefits to BTK inhibitors and the animal models of Alzheimers (p6431-32, ¶6) and where neuroinflammation is a is a key target in CNS disorders due to “…BTK inhibition links different pathways to regulate immune responses and inflammation reactions in the scope of neurological diseases (Figure 2).” As disclosed in the introduction, BTK inhibitors have been tested and/or applied in the treatment of both inflammatory and auto-immune diseases such as rheumatoid arthritis, multiple schlerosis and systemic lupus erythematosus (p6427,¶2). Finally, Cao et al. recites where the combination of a BTK inhibitor in combination with a second compound, biomolecule or chemotherapeutic agent (as instant claims 9-10) has been evaluated in vivo and in vitro, as various test models. Specifically, disclosing where more recent testing due to ibrutinib resistance, it was determined that “…combinative therapy seemed to be a more feasible way.”, where the combination of ibrtinib and rituximab reached an 80% clinical response rate without dose-limiting toxicity (p6433, ¶1). Additional studies were conducted where the combination of rituximab/lenalidomide/ibrutinib also demonstrated positive treatment responses.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing dated of the claimed invention, to arrive at the instantly claimed invention where a BTK inhibitor that was administered for the treatment of cancer, would also treat be used for an associated neurodegenerative disorder (as instant claim 7) and/or an inflammatory disorder (as instant claim 8), and in combination comprising a second compound, biomolecule or chemotherapeutic agent.
Regarding claims 7-10 where Yu et al. recites the use of BTK inhibitors has been shown to have an impact on multiple pathways due to the presence of BTK across many cell lines and the BTK inhibitor ability to cross the BBB while demonstrating degradation across multiple cancer cell lines. Since BTK inhibitors have an impact both directly and indirectly on other pathways and included the treatment of neurodegenerative disorders (such as Alzheimer’s and MS) and inflammatory disorders (such as RA and SLE) it would have been obvious for one skilled in the art to use a BTK inhibitor to treat a person that has a disclosed form of cancer and a neurodegenerative disorder and/or inflammatory disorder because it has been demonstrated that treatments for multiple disorders can be achieved through a single treatment modality. Additionally, as demonstrated through studies, it is more feasible to use combination therapies with a second compound or therapeutic shows higher efficacy than using a BTK inhibitor only.
Summary of the Claims
Claims 1-13 are pending.
Claims 1-13 are rejected.
No claims are in condition for allowance.
Conclusion
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/S.H.D./Examiner, Art Unit 1627
/SAN MING R HUI/Primary Examiner, Art Unit 1627
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