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
The instant application claims priority to provisional application 63/163,326, filed on 03/19/2021, and is a CIP of application 17/698,956, filed on 03/18/2022.
Status of the Claims
Per Applicant’s amendment to the claims, submitted on 09/15/2023, claims 13, 15-17, 20, and 22-23 are amended. Currently, claims 1-23 are pending in the instant application.
Claim Rejections - 35 USC § 112 – Second Paragraph
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 1-13 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.
Each of claims 1-13 are indefinite for reciting the term “isomer” because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Under broadest reasonable interpretation, the term “isomer” could encompass any compounds having the same chemical formula as the target compounds, but having differing chemical structure. This term not only provides an overly broad genus of compounds, but makes unclear the genus of compounds being claimed. Accordingly, a person of ordinary skill in the art would not be able to readily or reasonably identify related species of compounds within such a broad scope.
Each of claims 1-13 are indefinite for reciting the term “prodrug” because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The term “prodrug” does not appear to be defined within the disclosure. Under broadest reasonable interpretation, the term “prodrug” could encompass any chemical precursors of a given compound, wherein said precursors are converted to the target compound upon metabolization in the body. Any such chemical precursor has not been defined within the claim with regards to structure or composition. Accordingly, a person of ordinary skill in the art would not readily or reasonably be able to identify any such prodrugs.
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.
(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.
Claim(s) 1-2, 5, 9 , and 31-21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bruncko (US 8563735 B2).
Claim 1 of the instant application recites a compound of Formula (I):
PNG
media_image1.png
135
483
media_image1.png
Greyscale
Bruncko teaches compounds as Bcl2 inhibitors, and methods of use of said compounds in the treatment of Bcl2 related diseases. Of the compounds taught by Bruncko, the following is of particular relevance (col. 22):
4-(4-((4'-chloro-1,1'-biphenyl-2-yl)methyl)piperazin-1-yl)- N-((3-nitro-4-((tetrahydro-2H-pyran-4-ylmethyl)amino) phenyl)sulfonyl)-2-phenoxybenzamide
A structural representation of the compound has been provided below for reference:
PNG
media_image2.png
274
505
media_image2.png
Greyscale
The compound of Bruncko anticipates a compound of Formula (I) wherein:
X is N
L is C1 alkylenyl
R1 is 6 membered heterocyclyl
R2 is aryl substituted by R7 wherein:
R7 is aryl, further substituted by R11 wherein:
R11 is halogen (Cl)
R3 is H
R4 is H
R5 is aryl
n is 0
Claim 2 further limits the compound of claim 1 wherein the compound of Formula (I) is a compound of Formula (I-A):
PNG
media_image3.png
227
493
media_image3.png
Greyscale
The compound of Bruncko anticipates a compound of Formula (I-A) wherein:
X is N
L is C1 alkylenyl
R1 is 6 membered heterocyclyl
R2 is aryl substituted by R7 wherein:
R7 is aryl, further substituted by R11 wherein:
R11 is halogen (Cl)
R3 is H
R4 is H
n is 0
X’ is CH
W is H
Y is H
r is 0
Claim(s) 3 and 1 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CAS Registry Number 1228940-92-8.
Claim 3 further limits the compound of claim 1 wherein the compound of Formula (I) is a compound of Formulas (I-A-1), (I-A-2), or (I-A-3):
PNG
media_image4.png
611
486
media_image4.png
Greyscale
CAS Registry Number 1228940-92-8 is a compound represented by the following chemical structure:
PNG
media_image5.png
354
640
media_image5.png
Greyscale
The above compound anticipates a compound of Formula (I-A-2) wherein:
X is N
L is C1 alkylenyl
R1 is 6 membered heterocyclyl
R2 is C6 cycloalkenyl substituted by three R7 groups wherein:
R7 is aryl, further substituted by R11 wherein:
R11 is halogen (Cl)
The remaining two R7 groups are C1 alkyl
R3 is H
R4 is H
n is 1
Claim(s) 4-5, 9, and 13-21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bruncko (previously referenced).
Claim 4 further limits the compound of claim 1 wherein the compound of Formula (I) is a compound of Formula (I-B-1) or (I-B-2):
PNG
media_image6.png
246
471
media_image6.png
Greyscale
The compound of Bruncko anticipates a compound of Formula (I-B-2) wherein:
L is C1 alkylenyl
R1 is 6 membered heterocyclyl
R2 is aryl substituted by R7 wherein:
R7 is aryl, further substituted by R11 wherein:
R11 is halogen (Cl)
R3 is H
R4 is H
R5 is aryl
n is 0
Claim 5 further limits the compound of claim 1 wherein the compound is a compound of Formula (I-C-1) or (I-C-2):
PNG
media_image7.png
252
497
media_image7.png
Greyscale
The compound of Bruncko anticipates a compound of both Formulas (I-C-1) and (I-C-2) wherein:
X is N
L is C1 alkylenyl
R2 is aryl substituted by R7 wherein:
R7 is aryl, further substituted by R11 wherein:
R11 is halogen (Cl)
R3 is H
R4 is H
R5 is aryl
n is 0
Claim 9 further limits the compound of claim 1 wherein the compound is a compound of Formula (I-G-1), (I-G-2), (I-G-3), or (I-G-4):
PNG
media_image8.png
470
496
media_image8.png
Greyscale
The compound of Bruncko anticipates a compound of formula (I-G-1) wherein:
R1 is 6 membered heterocyclyl
R2 is aryl substituted by R7 wherein:
R7 is aryl, further substituted by R11 wherein:
R11 is halogen (Cl)
R3 is H
R4 is H
R5 is aryl
n is 0
Claim 13 recites a pharmaceutical composition comprising the compound of claim 1, and a pharmaceutical carrier.
Bruncko teaches compositions comprising a combination of their compounds with excipients (i.e., carriers) (col. 49, lines 36-46)1.
Claim 14 further limits the composition of claim 13 wherein the composition comprises an additional pharmaceutically active agent.
Bruncko teaches compositions which comprise their taught compounds and additional pharmaceutically active agents (col. 49 lines 58-67, col. 50 lines 1-4)2.
Claim 15 recites a method of inhibiting Bcl-2, comprising administering to a subject in need of a treatment for cancer a compound of claim 1.
Bruncko teaches the administering of their compounds as Bcl-2 inhibitors for the treatment of patients with cancer (Col. 1, lines 49-59)3.
Claim 16 recites a method of treating a disease or disorder associated with the inhibition of Bcl-2, comprising administering to a subject in need of a treatment for cancer a compound of claim 1.
As discussed previously, Bruncko teaches the administering of their compounds as Bcl-2 inhibitors for the treatment of patients with cancer.
Claim 17 recites a method of treating cancer, comprising administering to a subject in need of a treatment for cancer a compound of claim 1.
As discussed previously, the teachings of Bruncko are directed towards administering their compounds for the treatment of Bcl-2 related cancers.
Claim 18 further limits the method of claim 17 wherein the cancer is selected from:
PNG
media_image9.png
207
588
media_image9.png
Greyscale
Bruncko teaches the treatment of various cancers including many of the same cancers as recited in the instant claim (col. 49):
PNG
media_image10.png
236
467
media_image10.png
Greyscale
Claim 19 further limits the method of claim 18 wherein the cancer is selected from marginal zone lymphoma (MZL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Bruncko teaches at least the treatment of follicular lymphoma and CLL.
Claim 20 further limits the method of claim 15 wherein the subject is a mammal.
Bruncko teaches administration to mammals (col. 125, lines 1-4)4.
Claim 21 further limits the method of claim 20 wherein the subject is a human.
The teachings of Bruncko are directed towards the treatment of various cancers and autoimmune diseases of humans.
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.
Claim(s) 22-23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bruncko (previously referenced) in view of Warren (Cell Death and Disease (2019) 10:177).
Claim 22 further limits the method of claim 15 wherein the Bcl-2 protein is isoform 1.
As discussed in the rejection of claim 15, the teachings of Bruncko anticipate a method of inhibiting Bcl-2 by administering a compound of claim 1 to a subject in need of cancer treatment. Bruncko does not explicitly teach the recited method wherein the Bcl-2 protein is isoform 1. However, it would be obvious to utilize the compounds of Bruncko to inhibit Bcl-2 isoform 1 because Warren teaches that isoform 1 of Bcl-2 has anti-apoptotic function.
Firstly, the teachings of Bruncko are directed towards the administration of Bcl-2 inhibitors for the treatment of Bcl-2 related diseases such as various cancers and autoimmune diseases. The principle behind the teachings of Bruncko is that the disclosed compounds inhibit the anti-apoptotic function of Bcl-2 proteins (col. 1, lines 11-16)5. Secondly, the teachings of Warren indicate that there are two isoforms of Bcl-2 protein; Bcl-2a (isoform 1) and Bcl-2B (isoform 2). The below table provides a brief summary (page 3 Table 2):
PNG
media_image11.png
296
507
media_image11.png
Greyscale
As indicated above, the Bcl-2a isoform provides anti-apoptotic activity and is highly expressed in B cell lymphomas. The teachings of align with the teachings of Bruncko, and it would have been obvious for a person of ordinary skill in the art to use the methods of Bruncko to inhibit Bcl-2a (isoform 1) because there would have been a reasonable expectation that inhibition of said protein isoform would ameliorate Bcl-2 related cancer by blocking the apoptotic function.
Claim 23 further limits the method of claim 15 wherein the Bcl-2 protein is isoform 2.
As discussed in the rejection of claim 15, the teachings of Bruncko anticipate a method of inhibiting Bcl-2 by administering a compound of claim 1 to a subject in need of cancer treatment. Bruncko does not explicitly teach the recited method wherein the Bcl-2 protein is isoform 1. However, it would be obvious to utilize the compounds of Bruncko to inhibit Bcl-2 isoform 2 because Warren teaches that both isoforms are identical save for a single exon which encodes for a transmembrane domain.
Firstly, the teachings of Bruncko are directed towards the administration of Bcl-2 inhibitors for the treatment of Bcl-2 related diseases such as various cancers and autoimmune diseases. The principle behind the teachings of Bruncko is that the disclosed compounds inhibit the anti-apoptotic function of Bcl-2 proteins (col. 1, lines 11-16)6. While Bruncko does not explicitly teach the differing isoforms, it is indicated that the disclosed compounds have binding affinity for Bcl-2. Looking towards the teachings of Warren, it is indicated that both isoforms of Bcl-2 are identical in structure, save for an exon encoding a transmembrane domain:
PNG
media_image11.png
296
507
media_image11.png
Greyscale
Furthermore, Warren indicates that the B isoform has a higher expression in leukemic patients. Absent of evidence of the contrary, a person of ordinary skill in the art would reasonably expect that the compounds disclosed by Bruncko as Bcl-2 inhibitors would have binding affinity for both isoforms of Bcl-2 due to their near identical structure.
Allowable Subject Matter
While the claims are not allowable in their current form, the individual compounds of claim 12 appear to be free of the art. Likewise, claims 6-8 and 10-11 provide sub-formulas of Formula (I) having corresponding R2/R3/R4 moieties not taught or reasonably suggested in the prior art. While Bcl-2 inhibitors with similar structure appear to be generally well known in the art (i.e., the previously referenced Bruncko and CAS Registry entries), the compounds of the aforementioned claims appear to at least lie outside the range of compounds established by the prior art.
Conclusion
Claims 1-23 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIC TRAN whose telephone number is (571)272-7854. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “Another embodiment pertains to a composition for treating bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoid malignancies of T-cell or B-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, nonsmall cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small cell lung cancer or spleen cancer, said composition comprising an excipient and a therapeutically effective amount of the compound of Formula (I).”
2 “Another embodiment pertains to a composition for treating bladder cancer, brain cancer, breast cancer, bone marrow cancer, cervical cancer, chronic lymphocytic leukemia, colorectal cancer, esophageal cancer, hepatocellular cancer, lymphoblastic leukemia, follicular lymphoma, lymphoid malignancies of T-cell or B-cell origin, melanoma, myelogenous leukemia, myeloma, oral cancer, ovarian cancer, nonsmall cell lung cancer, chronic lymphocytic leukemia, myeloma, prostate cancer, small cell lung cancer or spleen cancer, said composition comprising an excipient and a therapeutically effective amount of the compound of Formula (I).”
3 “Accordingly, the inventors have discovered that while compounds taught in the art have utility for the treatment of various cancers and immune diseases, they are not selective for anti-apoptotic Bcl-2 proteins over anti-apoptotic Bcl-Xi proteins and thereby result in a higher probability of side effects characterized by inhibition of anti-apoptotic Bcl-Xi proteins such as, thrombocytopenia. This invention therefore comprises a series of compounds that demonstrate unexpected properties with respect to their selectivity for binding to, and inhibiting the activity of antiapoptotic Bcl-2 protein”
4 “Still another embodiment comprises methods of treating cancer in a mammal comprising administering thereto a therapeutically acceptable amount o f a compound having Formula (I).”
5 “This invention pertains to compounds which selectively inhibit the activity of anti-apoptotic Bcl-2 family proteins, compositions containing the compounds, and methods of treating diseases during which anti-apoptotic Bcl-2 proteins are expressed.”
6 “This invention pertains to compounds which selectively inhibit the activity of anti-apoptotic Bcl-2 family proteins, compositions containing the compounds, and methods of treating diseases during which anti-apoptotic Bcl-2 proteins are expressed.”
Prosecution Insights