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 .
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 12/10/2025 has been considered.
Claim Status
The claim set and Applicant’s remarks filed on December 10, 2025 have been entered. Claims 4-5, 7, 10-11, 15, 17, 20, 24-25 and 27-29 are canceled. Thus, claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32 as amended are examined on the merits herein.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the non-final office action on June 11, 2025:
(I) The objections to claims 16, 21-22 and 30-31 are all withdrawn in view of Applicant’s amendments to claims 16, 21-22 and 30-31.
(II) The rejection of claim 31 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of Applicant’s amendment to claim 31.
Response to Arguments
(I) The rejection of claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32 on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 12,064,445;
(II) The rejection of claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32 on the ground of nonstatutory double patenting as being unpatentable over U.S. Patent No. 11,058701; and
(III) The provisional rejection of claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32 on the ground of nonstatutory double patenting as being unpatentable over co-pending application No. 17/797,443 are maintained.
Applicant argues:
(A) The heart of the current disclosure relates to a regimen were an initial therapy is administered until the subject is in remission and the subsequent therapy is administered while the subject is in remission, see Applicant’s arguments, pg. 9 , paragraph 1; pg. 10, fifth paragraph from the page; and pg. 11, last paragraph of the page.
(B) Yakar does not teach any specific regimen for administering during remission, see Applicant’s arguments, pg. 9, paragraph 2; pg. 10, fourth paragraph from the bottom of the page; and pg. 12, paragraph 1.
(C) There is no disclosure nor teaching in ‘445 nor in Yakar, respectively, of a specific regimen, moreover, a specific regimen for the treatment during two distinct period - before and during remission, see Applicant’s arguments, pg. 9, paragraph 3; pg. 10, third paragraph from the bottom of the page; and pg. 12, paragraph 2.
With respect to Applicant’s arguments (A)-(C), the Examiner respectfully notes Yakar teaches combination therapies of a cytarabine conjugate and one or more anti-neoplastic agents for inhibiting cancer cell growth, wherein in particular the conjugate is a conjugate of cytarabine and aspartic acid (BST-236) for use in the treatment of hematological cancers.
Yakar teaches BST-236 is also known as Asp-Cyt or Asp-Cytarabine; and where Yakar teaches pharmaceutical compositions comprising Asp-Cytarabine.
Yakar teaches the pharmaceutical compositions are administered every day or twice a week until the patient is cured or in remission.
Yakar also teaches combination therapy refers to the use of two or more kinds of therapies wherein the different kinds of therapies may be used in sequence in various timing formats.
Yakar further teaches the pharmaceutical composition is used for preventing recurrence of cancer, and said composition can be administered regularly for prolonged periods of time according to the clinician’s instructions.
The Examiner respectfully notes all of these teachings are discussed in greater detail in the maintained double patenting rejections below.
Additionally, Applicant’s arguments (A)-(C) are not particularly persuasive in view of the recitations of instant claim 1 as a whole; as the Examiner respectfully notes instant claim 1 recites a method of treating a hematological cancer in a subject which requires administering at least one initial therapy course and at least one subsequent therapy course.
Moreover, the Examiner also respectfully notes instant claim 1 only further requires that a composition comprising aspacytarabine be administered within (i) the at least one initial therapy course, or (ii) the at least one subsequent therapy course; or (iii) within both therapy courses.
The Examiner further respectfully notes the teachings of Yakar as discussed above teach limitations (i)-(iii).
Furthermore, in response to applicant's arguments that Yakar does not teach a specific regimen during remission; a specific regimen; or a specific regimen during two distinct periods - before and during remission as recited within either Applicant's argument (B) or (C) as discussed above, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Thus, Applicant’s arguments (A)-(C) have been fully considered but are not found persuasive.
(IV) The rejection of claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32 under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious is maintained.
Applicant reiterates arguments (A)-(C) as discussed above, see Applicant’s arguments, pg. 14, paragraph 3; pg. 15, last paragraph of the page; and pg. 16, paragraph 1, respectively.
The Examiner reiterates the notes made and discussed above regarding arguments (A)-(C) above and further reiterates arguments (A)-(C) are not found persuasive.
Applicant further argues:
(D) The sequence and timing in which therapies are administered after remission becomes crucial, see Applicant’s remarks, pg. 14, paragraph 4.
(E) Drug sequencing matters because post-remission phases of consolidation, intensification and maintenance are designed to target specific vulnerabilities of minimal residual disease (MRD) cells.
Accordingly, Applicant then argues this is why hematological oncology protocols specify not just the drugs to use, but the exact order and timing in which they must be delivered. See Applicant’s remarks, pg. 14, second paragraph from the bottom of the page.
(F) Post-remission therapy in hematological cancers is best understood as a carefully timed therapeutic choreography intended to prevent relapse, see Applicant’s remarks, pg. 14, last paragraph of the page.
(G) Drug sequencing during remission directly influences long-term survival, see Applicant’s remarks, pg. 15, paragraph 1.
With respect to Applicant’s arguments (D)-(G), the Examiner respectfully reiterates Yakar teaches combination therapies of a cytarabine conjugate and one or more anti-neoplastic agents for inhibiting cancer cell growth, wherein in particular the conjugate is a conjugate of cytarabine and aspartic acid (BST-236) for use in the treatment of hematological cancers.
Yakar teaches combination therapy refers to the use of two or more kinds of therapies wherein the different kinds of therapies may be used in sequence in various timing formats.
Yakar teaches the pharmaceutical compositions are administered every day or twice a week until the patient is cured or in remission.
Furthermore, Yakar teaches the pharmaceutical composition is used for preventing recurrence of cancer, and said composition can be administered regularly for prolonged periods of time according to the clinician’s instructions.
The Examiner also respectfully notes all of these teachings are discussed in greater detail in the maintained 102/103 rejection below.
Additionally, Applicant’s arguments (D)-(G) are not particularly persuasive in view of the recitations of instant claim 1 as a whole; as the Examiner respectfully notes instant claim 1 recites a method of treating a hematological cancer in a subject which requires administering at least one initial therapy course and at least one subsequent therapy course.
Moreover, the Examiner also respectfully notes instant claim 1 only further requires that a composition comprising aspacytarabine be administered within (i) the at least one initial therapy course, or (ii) the at least one subsequent therapy course; or (iii) within both therapy courses.
The Examiner further respectfully notes the teachings of Yakar as discussed above suggest that a pharmaceutical composition comprising a conjugate of cytarabine and aspartic acid (BST-236) (e.g. Asp-Cyt or Asp-Cytarabine) may be administered to a subject until they are cured or in remission and further teaches said composition comprising said conjugate may be used for preventing recurrence of cancer, for example preventing recurrence of cancer within the subject who is cured or in remission, wherein said composition of Yakar is regularly administered for prolonged periods of time according to the clinician’s instructions.
Accordingly, the Examiner respectfully notes to Applicant that the teachings of Yakar teach claim 1 by way of limitation (iii) as discussed above where both the initial therapy course and the subsequent therapy course comprise administering aspacytarabine as discussed above.
Furthermore, the Examiner respectfully notes to Applicant that instant claim 1 does not require a specific sequence of therapies; nor does instant claim 1 require specific timing or a specific time period for when said therapies are administered after remission.
The Examiner also respectfully notes the specific drug sequence of the at least one initial therapy course and the at least one subsequent therapy course as recited within instant claim 1 do not require any specific targeting step, for example in targeting specific vulnerabilities of minimal residual disease (MRD) cells as argued by Applicant within argument (E) as discussed above.
The Examiner respectfully notes instant claim 1 does not require said at least one subsequent therapy course intend to prevent relapse as argued by Applicant within argument (F) as discussed above.
Finally, the Examiner respectfully notes the method as recited within instant claim 1 does not require the at least one subsequent therapy course which is administered after the subject is in remission directly influence long-term survival as argued by Applicant within argument (G) as discussed above.
Thus, Applicant’s arguments (D)-(G) have been fully considered but are not found persuasive.
Claim Rejections - 35 USC § 102/103
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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.
Claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32 remain rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Yakar et al. (Published 17 January 2019, WO-2019012328-A1, IDS filed 02/21/2023).
Regarding claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26, and 30-32, Yakar teaches combination therapies of a cytarabine conjugate and one or more anti-neoplastic agents for inhibiting cancer cell growth, wherein in particular the conjugate is a conjugate of cytarabine and aspartic acid (BST-236) for use in the treatment of hematological cancers, see abstract. Yakar teaches BST-236 is also known as Asp-Cyt or Asp-Cytarabine, see pg. 4, line 5. Yakar teaches pharmaceutical compositions comprising Asp-Cytarabine, see pg. 19, lines 28-29 (e.g., the composition required in claim 32).
The Examiner notes that BST-236 as taught by Yakar above meets all structural limitations of aspacytarabine as recited in instant claim 1, lines 7-9.
Yakar teaches combination therapy refers to the use of two or more kinds of therapies (e.g. an initial therapy course and a subsequent therapy course, required in claim 1, lines 2-3), wherein the different kinds of therapies may be used in sequence, at the same time, or in various timing formats, see, pg. 33, lines 23-25.
Yakar teaches the pharmaceutical compositions are administered every day or twice a week until the patient is cured or in remission (e.g. the at least one initial therapy course required in claim 1, lines 3-4; and the number of courses of the initial therapy, required in claim 16, lines 1-2), see pg. 51, lines 9-14. Yakar also teaches the pharmaceutical composition is used for preventing recurrence of cancer, and said composition can be administered regularly for prolonged periods of time according to the clinician’s instructions (e.g. the at least one subsequent therapy course required in claim 1, lines 4-5 and the number of courses of the subsequent therapy, required in claim 16, lines 3-4), see pg. 51, lines 15-17.
Yakar teaches combination therapies for the treatment of hematological malignancies can include co-administration or sequential administration of the following anti-neoplastic drugs which include the combinations of Asp-Cytarabine + azacitidine and Asp-Cytarabine + venetoclax (ABT-199), see pg. 44, lines 9-15.
The Examiner notes that both therapy courses:
comprise Asp-Cytarabine, as required in claims 1 and 3;
comprise at least one anti-hematological cancer agent, required in claim 2;
wherein at least one initial therapy course comprises administering at least one anti-hematological cancer agent that is not aspacytarabine, required in claim 6;
comprises administering aspacytarabine or at least one anti-hematological cancer agent that is not aspacytarabine, required in claim 8;
comprises administering at least two anti-hematological cancer agents, wherein one of said anti-hematological cancer agent is aspacytarabine and one is not aspacytarabine, required in claim 9;
said at least one initial therapy course comprises administering aspacytarabine and at least one additional anti-hematological cancer agent and said at least one subsequent therapy course comprises administering aspacytarabine and at least one additional anti-hematological cancer agent, wherein the at least one additional anti-hematological cancer agent in the initial and subsequent therapy is the same or different, required in claim 12;
said at least one initial therapy course comprises administering aspacytarabine and at least one additional anti-hematological cancer agent; and wherein said at least one subsequent therapy course comprises aspacytarabine, required in claim 13;
said at least one initial therapy comprises administering at least one anti-hematological cancer agent other than aspacytarabine; and wherein said at least one subsequent therapy course comprises aspacytarabine and optionally at least one additional anti-hematological cancer agent, required in claim 14; and
wherein said at least one subsequent therapy course comprises administering at least one anti-hematological cancer agent selected from and including venetoclax, aspacytarabine, and azacitidine, required in claim 30.
Yakar teaches hematological disorders are selected from the group consisting of leukemias, lymphomas, multiple myeloma, and Myelodysplastic Syndromes (MDS), see pg. 27, lines 4-6.
Yakar teaches leukemia is selected from the group consisting of Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Chronic Myeloid Leukemia (CML), and Chronic Lymphoblastic Leukemia (CLL), see pg. 27, lines 7-9.
Yakar teaches lymphoma is selected from the group consisting of Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma (NHL), see pg. 27, lines 12-13.
Yakar teaches azacitidine is a hypomethylating agent, see pg. 13, line 25 - pg. 14, line 1. Yakar teaches venetoclax (ABT-199) is a Bcl-2 inhibitor, see pg. 15, line 3.
Yakar teaches Asp-Cytarabine is administered in a daily dose from about 0.3 g/m2 to about 10 g/m2, such as a daily dose of about 6 g/m2, see pg. 20, lines 8-12.
Yakar teaches the Asp-Cytarabine daily dose may be reduced when administered with at least one additional neoplastic agent, wherein a reduction in the Asp-Cytarabine dose may be facilitated due to synergistic therapeutic activity observed when Asp-Cytarabine is used in combination with the at least one additional anti-neoplastic agent, see pg. 44, lines 3-8.
Yakar defines synergistic effect includes the effect achieved with the combination of BST-236 or (a salt thereof) and at least one additional antineoplastic agent (e.g. azacitidine), for example overall survival, see pg. 32, lines 21-29; and that synergy provides greater efficacy at the same doses or lower doses and reduced side effects, see pg. 37, lines 3-5, (e.g. wherein the treatment improves at least one clinical condition required in claim 31).
Claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32 appear to be anticipated by Yakar, however, alternatively, the claims are prima facie obvious over Yakar; as Yakar teaches administering BST-236 or Asp-Cytarabine, which corresponds to aspacytarabine in instant claim 1, lines 7-9, as a combination therapy by using two or more kinds of therapies that may be used in sequence, at the same time, or in various timing formats, as discussed above.
In addition, Yakar teaches pharmaceutical compositions containing Asp-Cytarabine, specifically Asp-Cytarabine + azacitidine and Asp-Cytarabine + venetoclax (ABT-199) that can be sequentially administered as discussed above.
Moreover, Yakar teaches administering the pharmaceutical composition every day or twice a week until the patient is cured or in remission; and the pharmaceutical composition is used for preventing recurrence of cancer, and said composition can be administered regularly for prolonged periods of time according to the clinician’s instructions as discussed above.
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have administered the combination therapy of Asp-Cytarabine + azacitidine or Asp-Cytarabine + venetoclax as an initial therapy course unit the patient is in remission; or to have administered either combination discussed above as a subsequent therapy course to the patient while said patient was in remission as Yakar teaches above.
One of ordinary skill in the art would have been motivated to use either combination discussed above as an initial or subsequent therapy course in order to treat the hematological cancers of Yakar as discussed above. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success to have administered the combinations discussed above as either an initial or subsequent therapy course as Yakar teaches the pharmaceutical compositions comprising Asp-Cytarabine are administered until the patient is cured or in remission and can be used for preventing recurrence of cancer as discussed above.
Thus, the claimed invention as a whole appears to be anticipated by Yakar, however, alternatively, the claims would have been prima facie obvious over the teachings of Yakar as discussed above.
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.
(I) Claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 of U.S. Patent No. 12,064,445 (Applicant: Biosight Ltd., PTO-892 mailed 06/11/2025) in view of Yakar et al. (Published 17 January 2019, WO-2019012328-A1, IDS filed 02/21/2023). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are direct to treating hematological cancer by administering a composition comprising aspacytarabine.
Reference claim 1 recites a method of treating an acute myeloid leukemia (AML), an acute lymphocytic leukemia (ALL), a Chronic Myeloid Leukemia (CML), a Chronic Lymphocytic Leukemia (CLL), a lymphoma, a myeloma, or a Myelodysplastic Syndrome (MDS) in a subject in need thereof, comprising administering a compound represented by the structure of formula (I); a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising said compound or its pharmaceutically acceptable salt thereof; wherein the therapeutically effective amount of said compound is administered at a daily dose of from 0.3 g/m2 to 6 g/m2, thus providing reduce adverse effects of the compound compared to the adverse effects of standard or higher doses of the non-conjugated cytarabine.
Reference claim 4 recites the therapeutically effective amount of the compound is administered daily.
The Examiner notes that the structure of formula (I) depicts a cytarabine conjugated with an aspartic acid. The Examiner also notes that the Specification discloses “treating” is meant to include reversing the progression of the disease, see Col. 12, lines 4-6. The Examiner reasonably interprets the phrase “reversing the progression of the disease” to include remission as required in instant claim 1, line 4.
Although, ‘445 does not recite (a) wherein both therapy courses comprise administering the specific stereoisomer of cytarabine conjugated with an aspartic acid as defined as aspacytarabine, required in instant claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32; (b) at least one anti-hematological cancer agent, required in instant claims 2, 6, 9, 12-14, 21-23 and 30; (c) the number of courses for the initial and subsequent therapies, required in instant claim 16; and (d) the treatment improves at least one clinical condition, required in instant claim 31.
However, in the same field of endeavor of treating hematological cancer, with respect to limitations (a)-(d), Yakar teaches combination therapies of a cytarabine conjugate and one or more anti-neoplastic agents for inhibiting cancer cell growth, wherein in particular the conjugate is a conjugate of cytarabine and aspartic acid (BST-236) for use in the treatment of hematological cancers, see abstract. Yakar teaches BST-236 is also known as Asp-Cyt or Asp-Cytarabine, see pg. 4, line 5. Yakar teaches pharmaceutical compositions comprising Asp-Cytarabine, see pg. 19, lines 28-29 (e.g., the composition required in claim 32).
The Examiner notes that BST-236 as taught by Yakar above meets all structural limitations of aspacytarabine as recited in instant claim 1, lines 7-9.
Yakar teaches combination therapy refers to the use of two or more kinds of therapies, wherein the different kinds of therapies may be used in sequence, at the same time, or in various timing formats, see, pg. 33, lines 23-25.
Yakar teaches the pharmaceutical compositions are administered every day or twice a week until the patient is cured or in remission (e.g. the at least one initial therapy course required in instant claim 1, lines 3-4; and the number of courses of the initial therapy, required in instant claim 16, lines 1-2), see pg. 51, lines 9-14. Yakar teaches the pharmaceutical composition is used for preventing recurrence of cancer, and said composition can be administered regularly for prolonged periods of time according to the clinician’s instructions (e.g. the at least one subsequent therapy course required in instant claim 1, lines 4-5 and the number of courses of the subsequent therapy, required in instant claim 16, lines 3-4), see pg. 51, lines 15-17.
Yakar teaches combination therapies for the treatment of hematological malignancies can include co-administration or sequential administration of the following anti-neoplastic drugs which include the combinations of Asp-Cytarabine + azacitidine and Asp-Cytarabine + venetoclax (ABT-199), see pg. 44, lines 9-15.
Yakar teaches hematological disorders are selected from the group consisting of leukemias, lymphomas, multiple myeloma, and Myelodysplastic Syndromes (MDS), see pg. 27, lines 4-6.
Yakar teaches leukemia is selected from the group consisting of Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Chronic Myeloid Leukemia (CML), and Chronic Lymphoblastic Leukemia (CLL), see pg. 27, lines 7-9.
Yakar teaches lymphoma is selected from the group consisting of Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma (NHL), see pg. 27, lines 12-13.
Yakar teaches azacitidine is a hypomethylating agent, see pg. 13, line 25 - pg. 14, line 1. Yakar teaches venetoclax (ABT-199) is a Bcl-2 inhibitor, see pg. 15, line 3.
Yakar teaches the Asp-Cytarabine daily dose may be reduced when administered with at least one additional neoplastic agent, wherein a reduction in the Asp-Cytarabine dose may be facilitated due to synergistic therapeutic activity observed when Asp-Cytarabine is used in combination with the at least one additional anti-neoplastic agent, see pg. 44, lines 3-8.
Yakar defines synergistic effect includes the effect achieved with the combination of BST-236 or (a salt thereof) and at least one additional antineoplastic agent (e.g. azacitidine), for example overall survival, see pg. 32, lines 21-29; and that synergy provides greater efficacy at the same doses or lower doses and reduced side effects, see pg. 37, lines 3-5, (e.g. wherein the treatment improves at least one clinical condition required in instant claim 31).
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included limitations (a)-(d) into the method recited in ‘445 as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to treat the hematological cancers as recited in reference claim 1 of ‘445 by specifically reversing the progression of the disease as defined in the Specification of ‘445 discussed above, as the combination therapies taught by Yakar are used to treat the same hematological cancers as recited in the instant claims. One of ordinary skill in the art would have had a reasonable expectation of success to have included limitations (a)-(d) into the method recited by ‘445, as both ‘445 and Yakar are directed to treating the hematological cancers with pharmaceutical compositions of cytarabine conjugated with an aspartic acid; and wherein Yakar teaches their pharmaceutical compositions are administered until the patient is cured or in remission and can be used for preventing recurrence of cancer.
Therefore, the claimed invention as a whole would have been prima facie obvious over the combined recitations of ‘445 and the teachings of the prior art.
(II) Claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4 and 6-8 of U.S. Patent No. 11,058,701 (Applicant: Biosight Ltd., PTO-892 mailed 06/11/2025) in view of Yakar et al. (Published 17 January 2019, WO-2019012328-A1, IDS filed 02/21/2023). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are direct to treating hematological cancer by administering a composition comprising aspacytarabine.
Reference claim 1 recites a method of treating a neoplastic disease in a subject in need thereof, comprising administering to the subject a compound represented by the structure of formula (I); a pharmaceutically acceptable salt thereof; or a pharmaceutical composition comprising said compound or its pharmaceutically acceptable salt; wherein the therapeutically effective amount of said compound is administered at a daily dose of from 2.5 g/m2 to 10 g/m2, and wherein adverse effects of the compound are reduced compared to the adverse effects of standard or higher doses of the non-conjugated cytarabine.
Reference claim 4 recites wherein the therapeutically effective amount of the compound is administered daily.
Reference claim 6 recites wherein the neoplastic disease is a hematological cancer.
Reference claim 7 recites wherein the hematological cancer is leukemia, a lymphoma, a myeloma, or a Myelodysplastic Syndrome (MDS).
Reference claim 8 recites wherein the leukemia is acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), Chronic Myeloid Leukemia (CML), or Chronic Lymphocytic Leukemia (CLL).
The Examiner notes that the structure of formula (I) depicts a cytarabine conjugated with an aspartic acid. The Examiner also notes that the Specification discloses “treating” is meant to include reversing the progression of the disease, see Col. 11, lines 11-13. The Examiner reasonably interprets the phrase “reversing the progression of the disease” to include remission as required in instant claim 1, line 4.
Although, ‘701 does not recite (a) wherein both therapy courses comprise administering the specific stereoisomer of cytarabine conjugated with an aspartic acid as defined as aspacytarabine, required in instant claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32; (b) at least one anti-hematological cancer agent, required in instant claims 2, 6, 9, 12-14, 21-23 and 30; (c) the number of courses for the initial and subsequent therapies, required in instant claim 16; and (d) the treatment improves at least one clinical condition, required in instant claim 31.
However, in the same field of endeavor of treating hematological cancer, with respect to limitations (a)-(d), Yakar addresses limitations (a)-(d) as discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included limitations (a)-(d) into the method recited in ‘701 as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to treat the neoplastic disease as recited in reference claim 1 of ‘701, particularly the hematological cancers recited in reference claims 6-8 by specifically reversing the progression of the disease as defined in the Specification of ‘701 discussed above, as the combination therapies taught by Yakar are used to treat the same hematological cancers as recited in the instant claims. One of ordinary skill in the art would have had a reasonable expectation of success to have included limitations (a)-(d) into the method recited by ‘701, as both ‘701 and Yakar are directed to treating the hematological cancers with pharmaceutical compositions of cytarabine conjugated with an aspartic acid; and wherein Yakar teaches their pharmaceutical compositions are administered until the patient is cured or in remission and can be used for preventing recurrence of cancer.
Therefore, the claimed invention as a whole would have been prima facie obvious over the combined recitations of ‘701 and the teachings of the prior art.
(III) Claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32, 43 and 45 of copending Application No. 17/797,443 (amended claim set filed 08/04/2022, Applicant: BioSight Ltd.) in view of Yakar et al. (Published 17 January 2019, WO-2019012328-A1, IDS filed 02/21/2023). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are direct to treating hematological cancer by administering a composition comprising aspacytarabine.
Reference claim 43 recites a method of treating a neoplastic disease comprising administering to a subject in need of such treatment a composition according to claim 32.
Reference claim 45 recites the composition is administered at a daily dose wherein the aspacytarabine dosage is ranging from about 0.3 g/m2 to about 10 g/m2 for a period of at least 3 days.
Reference claim 32 recites a composition comprising aspacytarabine or a pharmaceutically acceptable salt thereof and at least one water soluble stabilizer and/or solubilizer.
The Examiner notes that the Specification discloses “treating” is meant to include reversing the progression of the disease, see paragraph [0072], lines 1-2. The Examiner reasonably interprets the phrase “reversing the progression of the disease” to include remission as required in instant claim 1, line 4.
Although, ‘443 does not recite the initial therapy course and the subsequent therapy course, required in instant claims 1-3, 6, 8-9, 12-14, 16, 18-19, 21-23, 26 and 30-32.
However, in the same field of endeavor of treating hematological cancer, with respect to the initial and subsequent therapy courses, Yakar addresses the initial and subsequent therapy courses as discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included the initial and subsequent therapy courses into the method recited in ‘443 as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to treat the neoplastic disease as recited in reference claim 43 of ‘443 by specifically reversing the progression of the disease as defined in the Specification of ‘443 discussed above, as the combination therapies taught by Yakar are used to treat neoplastic diseases as discussed above. One of ordinary skill in the art would have had a reasonable expectation of success to have included the initial and subsequent therapies into the method recited by ‘443, as both ‘443 and Yakar are directed to treating neoplastic diseases with compositions of aspacytarabine as discussed above; and wherein Yakar teaches their pharmaceutical compositions are administered until the patient is cured or in remission and can be used for preventing recurrence of cancer.
Therefore, the claimed invention as a whole would have been prima facie obvious over the combined recitations of ‘443 and the teachings of the prior art.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed in this action.
THIS ACTION IS MADE FINAL. 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.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691