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
Instant application 18/834,562 filed on 07/30/2024 claims benefit as follow:
CONTINUING DATA:
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Status of the Application
Claims 1-12 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/30/2024 was in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Written Description
Claims 1-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, claims 1-12 are drawn to “byrostatin compound” (claim 1) and “byrostatin-1 or a byrostatin analog” (claim 2).
Byrostatin-1 is a known compound that is structurally defined. However, the genus of “byrostatin compound” and “analog” of bryostatin is not fully structurally defined.
The terms “bryostatin compound” and “bryostatin analog” in the claims could be interpreted as referring to structural and functional analogs. It is unclear what is encompassed by the terms “bryostatin compound” and “analog”.
The specification provides a definition for a “byrostatin compound” as follows (see para [0030-0031]):
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It should be noted that the provided definition of byrostatin compounds is not exclusive or limiting because the definition includes derivative compounds defined only by function as “compounds that retain functionality required for biological activity” (see para. [0031]).
Wu (Wu R, et al., Chemistry. 2020 Jan 27;26(6):1166-1195. Epub 2019 Nov 19) teaches “Bryostatins, as a class of macrolide compounds with highly promising biological activity and medicinal value, have been widely demanded in the fields of natural product synthesis and biomedicine. A large number of remarkable works on bryostatins have emerged since 1986. The brief synthetic history of bryostatins is as follows: 1) 1990—the first total synthesis (79 steps) of the bryostatin derivative bryo 7 was reported by Masamune et al.; 2) 2011—a big year for bryostatins when three total syntheses (bryo 1 in 58 steps, bryo 9 in 43 steps, and bryo 7 in 36 steps) were reported with the shortest one of only 36 total steps; and 3) 2017 and 2018—Wender et al. and Song et al. achieved the synthesis of bryo 1 on the multi-gram level and the synthesis of bryo 8, respectively.”
Furthermore, Wender (Wender et al., Journal of Organic Chemistry (2020) 85 (23): 15116–15128) teaches simplified analogues of byrostatin (see Abstract and Figure 1):
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It should be noted that Wender teaches the above compounds still maintain function (biological activity). Wender teaches “These analogues, one without and one with a C26-methyl group, exhibit remarkably different protein kinase C (PKC) isoform affinities. The former exhibited bryostatinlike binding to several PKC isoforms with Ki’s < 5 nM, while the latter exhibited PKC affinities that were up to ∼180-fold less potent.” (see abstract).
However, it is not clear which further modification would lead to retention or loss of activity.
Methods of synthesizing compounds are, in general, known to the person of ordinary skill, however methods of making the myriad of compounds embraced by the instant claims is beyond the skill of the artisan, particularly when certain elements, such as “an analog” and “a derivative”, are merely described partially. As such, the instant specification and instant claims do not provide sufficient description such that one could anticipate what additional elements may be present in the analogs of bryostatin.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Dependent claims do not resolve these issues, since these claims do not further limit or provide further structure of the “analog”. Accordingly, these claims are also rejected.
The rejection would be overcome by amending the claims to add structural limitations necessary to perform the function. For example, a general formula could be added to claim 1.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 3 and 4 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 3 and 4 recite “time for administration”. The term “time for administration” is not clear.
For a purpose of a compact prosecution, the term is interpreted as time of exposure to bryostatin compound and duration of administrations of bryostatin compound.
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.
(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.
Claims 1-3 and 5-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Becker (WO-2021/072017-A1 Published 15 April 2021).
Becker teaches and claims:
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Regarding claim 3, Becker teaches 24 hours exposure:
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Regarding claim 5, Becker teaches and claims administering an immunotherapeutic agent to the subject (see claim 13 and para [0008]).
Regarding claim 6, Becker teaches and claims a method wherein the immunotherapeutic agent is administered prior to, simultaneously with or following administration of bryostatin-1 or a functional analog thereof (see claim 16).
Regarding claim 6, Becker teaches and claims hematological cancer selected from the group consisting of a B-cell lymphoma, a T-cell malignancy, non-Hodgkin's lymphoma (NHL), mantle cell lymphoma (MCL), multiple myeloma (MM), acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), myelodysplastic syndrome, acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and hairy cell leukemia (HCL) (see claim 14).
Regarding claim 8, Becker teaches and claims a method wherein the immunotherapeutic agent is selected from the group consisting of a monoclonal antibody, a bispecific antibody, an antibody-drug conjugate (ADC), a chimeric antigen receptor (CAR)-T cell, a chimeric antigen receptor natural killer (CAR-NK) cell, an anti-tumor vaccine or a combination thereof (see claim 15).
Regarding claim 9, Becker teaches the immunotherapeutic agent binds to or targets a protein selected from CD19, CD20, CD22, CD33, CD37, CD38, CD123 and BCMA (see p.3, para. [0009]).
Regarding claim 10, Becker teaches a chemotherapeutic agent, an ADC, a vaccine, an immunomodulatory drug, an immune metabolism modifying drug, a targeted therapy, radiation, an anti-angiogenesis agent, CAR-T therapy, CAR-NK therapy, an agent that reduces immune-suppression, or a combination thereof (see para. [0008]).
Regarding claim 11, Becker teaches bispecific antibody (see para. [0011]).
Regarding claim 12, Becker teaches that the disclosed method is intended for treating humans (see para. [0047]).
Since the teachings of Becker meets all the limitations of instant claims 1-3 and 5-12, those claims are anticipated.
Claims 1, 2, 7, 10 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Varterasin (Varterasin, et al., Clin Cancer Res (2000) 6 (3): 825–828).
Varterasin discloses a phase II trial with byrostatin-1 in patients non-Hodgkin’s lymphoma or chronic lyphocytic leukemia (CLL) (see Abstract and Title). Varterasin teaches non-Hodgkin’s V teaches patients who progressed while receiving bryostatin 1 alone could participate in a feasibility study by receiving vincristine administered by bolus i.v. injection immediately after the completion of the bryostatin 1 infusion (see abstract).
Regarding instant claim 10, Varterasin teaches chemotherapeutic agent, vincristine (see abstract). Further, Varterasin teaches dolastatin 10 (a natural product derived from the shell-less marine mollusk Dolabela auricularia that is currently in Phase II clinical trials) and its structural homologue, auristatin PE, alone and in combination with bryostatin 1 (see p. 828, first paragraph),
Since the teachings of Varterasin meets all the limitations of instant claims 1, 2, 10 and 12, those claims are anticipated.
Claims 1-3, 5-10 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Biberacher (Biberacher V, et al., Haematologica. 2012 May;97(5):771-9).
Biberacher teaches that bryostatin 1 sensitizes chronic lymphocytic leukemia cells for the cytotoxic effects of BL22 through activation of protein kinase C and subsequently increased CD22 surface expression (see Abstract, Results).
Regarding claim 3, Biberacher teaches CLL cells exposed to bryostatin 1 for 24 h. (see Figure 3).
Regarding claim 7, Biberacher teaches B-cell lymphomas (see title).
Biberacher teaches that combination of bryostatin 1 and BL22 is highly effective in low- and high-risk patients (see p. 772, end of last paragraph and Supplementary Table S1.).
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Regarding claim 8 and 10, Biberacher teaches that BL22 is a monoclonal antibody directed against CD22 and fused to a truncated Pseudomonas exotoxin (see p.776, second paragraph).
Regarding claim 9, Biberacher teaches that BL22 binds to CD22 (see p. 771, second paragraph).
Regarding instant claim 12, it should be noted that Biberacher teachings is intended for humans (see p.771, Background). MPEP 2131.02 III sates that a reference disclosure can anticipate a claim when the reference describes the limitations but ”d[oes] not expressly spell out' the limitations as arranged or combined as in the claim, if a person of skill in the art, reading the reference, would ‘at once envisage’ the claimed arrangement or combination." In the instant case a person of ordinary skill in the art would ‘at once envisage’ administering bryostatin-1 and BL22 to a human subject because Biberacher teaches the method is intended for patients suffering from chronic lymphocytic leukemia, “treatment remains palliative and all patients frequently relapse” (see Background).
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.
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 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over by Becker (WO-2021/072017-A1 Published 15 April 2021) in view of Alkon (WO 2019/222564-A1).
The teachings of Becker have been discussed above and those teachings are incorporated herein by reference.
Regarding claim 4, Becker does not teach the time for administration is about 30 min, about 45 min, about 1hr, about 2hr, or about 3 hr.
However, Alkon teaches administration of byrostatin-1 by continuous infusion over 45 minutes (see p. 30, para. [0092]).
Therefore, it would be prima facie obvious to a person of ordinary skill in the art to modify the method disclosed by Becker to include intravenous administration by infusion over 45 minutes as disclosed by Alkon. The skilled artisan would be motivated to provide easy access to the circulatory system via intravenous infusion. In addition, the skilled artisan would be motivated to decrease adverse reaction with shorter exposure time.
In addition, a person of ordinary skill before the effective filing date of the instant application would have been capable to adjust time for administration by routine experimentation. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Please see MPEP 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Claims 1-4, 7, 10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over by Varterasin (Varterasin, et al., Clin Cancer Res (2000) 6 (3): 825–828) in view of Haas (Haas NB, et al., Clin Cancer Res. 2003 Jan;9(1):109-14.).
The teachings of Varterasin have been discussed above and those teachings are incorporated herein by reference.
Varterasin teaches that toxicity of bryostatin can be controlled by dose reduction and/or dose delays (see p. 827, last paragraph):
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Regarding claims 3 and 4, Varterasin does not teach the time for administration is about 0.5 to 24 hours.
The deficiency is cured by Haas.
Haas teaches treatment of patients with metastatic renal carcinoma with bryostatin-1, wherein byrostatin-1 is infused over 1 hour (see p. 113, second paragraph).
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Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Varterasin to include administration by infusion over 1 hour as disclosed by Haas. The skilled artisan would be motivated to provide easy access to the circulatory system via intravenous infusion. In addition, the skilled artisan would be motivated to decrease adverse reaction with shorter exposure time.
In addition, a person of ordinary skill before the effective filing date of the instant application would have been capable to adjust time for administration by routine experimentation. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Please see MPEP 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.
Claims 1-10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Biberacher (Biberacher V, et al., Haematologica. 2012 May;97(5):771-9) in view of Haas (Haas NB, et al., Clin Cancer Res. 2003 Jan;9(1):109-14.).
Biberacher teaches that bryostatin 1 sensitizes chronic lymphocytic leukemia cells for the cytotoxic effects of BL22 through activation of protein kinase C and subsequently increased CD22 surface expression (see Abstract, Results).
Regarding claim 3, Biberacher teaches CLL cells exposed to bryostatin 1 for 24 h. (see Figure 3).
Regarding claim 7, Biberacher teaches B-cell lymphomas (see title).
Biberacher teaches that combination of bryostatin 1 and BL22 is highly effective in low- and high-risk patients (see p. 772, end of last paragraph).
Regarding claim 8 and 10, Biberacher teaches that BL22 is a monoclonal antibody directed against CD22 and fused to a truncated Pseudomonas exotoxin (see p.776, second paragraph).
Regarding claim 9, Biberacher teaches that BL22 binds to CD22 (see p. 771, second paragraph).
Regarding claim 4, Biberacher does not teach the time for administration is about 30 min, 45 min, 1hr, 2hr or 3 hours.
Regarding the time of administration, the deficiency is cured by Haas.
Haas teaches treatment of patients with metastatic renal carcinoma with bryostatin-1, wherein byrostatin-1 is infused over 1 hour (see p. 113, second paragraph).
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Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method disclosed by Biberacher to include administration by infusion over 1 hour because Haas discloses byrostatin-1 infused over 1 hour. The skilled artisan would be motivated to provide easy access to the circulatory system via intravenous infusion. In addition, the skilled artisan would be motivated to decrease adverse reaction with shorter exposure time.
In addition, a person of ordinary skill before the effective filing date of the instant application would have been capable to adjust time for administration by routine experimentation. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Please see MPEP 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation
Conclusion
No claim is allowed.
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/I.S./Examiner, Art Unit 1621
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
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