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 .
Election/Restrictions
Applicant’s election without traverse of claims 1-12 (Group I) in the reply filed on 04/06/2026 is acknowledged. Claims 2, 3, 5, 6, and 8 were cancelled in the reply filed 04/06/2026. Accordingly, Group I includes claims 1, 4, 7, and 9-12, as reflected in the amended claim set filed 04/06/2026.
Withdrawn claims 13-24 were cancelled in the reply filed 04/06/2026.
Election was made without traverse in the reply filed 04/06/2026.
Accordingly, claims 1, 4, 7, and 9-12 are pending and under consideration.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos. 63/141,333, 63/274,331, and PCT/US2022/013333, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application for the reasons given below in the rejections under 35 U.S.C. 112(a) or 35 U.S.C.112 (pre-AIA ), first paragraph.
Accordingly, claims 1, 4, 7, and 9-12 have an effective filing date of 01/21/2022, which is the filing date of PCT/US2022/013333.
Information Disclosure Statement
Receipt of information disclosure statements on 06/07/2024, 06/16/2025, and 06/20/2025 is acknowledged. The signed and initialed PTO-1449‘s have been mailed with this action.
Drawings
The drawings filed 07/07/2023 are acceptable.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at paragraph [00295]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 9 is objected to because of the following informalities:
Claim 9 recites “the method of claim 7, wherein the genotyping determines the presence of driver mutations in one or more of TET2, ASXL1, SF3B1, SRSF2, TP53, JAK2, PPM1D, NRAS, KRAS, IDH1, and IDH2 prior to treatment, and found to have at least one driver mutation” (bolded emphasis added), which is phrased poorly such that interpretation is cumbersome. For purposes of internal consistency and ease of interpretation, it would be remedial to amend the instant claim. An example of such an amendment is “the method of claim 7, wherein the genotyping determines the presence of driver mutations in one or more of TET2, ASXL1, SF3B1, SRSF2, TP53, JAK2, PPM1D, NRAS, KRAS, IDH1, and IDH2 prior to treatment, and wherein the individual is found to have at least one driver mutation” (bolded and underlined emphasis added). However, this is merely an example set forth by the Examiner and Applicant is invited to amend the instant claim language in accordance with the scope of protection sought and in accordance with standard grammatical and/or linguistic conventions.
Appropriate correction is required.
Claim Interpretation
The Examiner notes that independent claim 1 is drawn to a method, wherein the only method step recited is “administering an effective dose of an agent that inhibits expression or activity of TCL1A.” Dependent claim 4 and 10 further limit this method step, while dependent claims 7, 9, 11, and 12 limit the preamble of independent claim 1, which is not given patentable weight as it is drawn to an intended use. Therefore, any rejection over independent claim 1 must also applied to dependent claims 7, 9, 11, and 12, as none of these recitations further limit the required steps of the claimed method.
The Examiner notes that both instant claims 11 and 12 recite “wherein the treatment provides for a reduction in development of…” various diseases. Under broadest reasonable interpretation, this limitation has been interpreted to encompass the prevention of various diseases. The instant specification does not offer any clarifying definition of “reduction in development” and in fact explicitly discloses the prevention of diseases at paragraphs [0058] and [0059]. Accordingly, instant claims 11 and 12 have been interpreted to encompass the prevention of various diseases, as set forth in greater detail below.
Claim Rejections - 35 USC § 112(a) – Written Description
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.
Claims 1, 4, 7, and 9-12 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.
Claim 1, from which all other claims directly or indirectly depend, is drawn to a method for treating an individual for hematologic malignancies, including CHIP, to reduce clonal expansion, wherein said method comprises administering an effective dose of an agent that inhibits expression or activity of TCL1A. Thus, claim 1 is drawn to a set of agents that inhibit expression or activity of TCL1A. These agents are further limited to small molecule drugs at instant claim 4. Dependent claim 10 further recites administration of additional agents or regimens useful in the treatment of hematologic malignancies. The rejected claims thus comprise a set of agents, including small molecule drugs, defined solely by their ability to function to inhibit the expression or activity of TCL1A, thereby treating hematologic malignancies and reducing clonal expansion. The agents of dependent claim 10 are broadly functionally claimed as being capable of treating hematologic malignancies, with no other structural or functional limitations recited. Overall, the rejected claims thus encompass a staggering breadth of possible therapeutic agents, all of which must function to treat hematologic malignancies and reduce clonal expansion by targeting TCL1A.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes identification of TCL1A as a factor underlying the clonal fitness advantage of several driver mutations in CHIP (paragraph [00187]). While Tables 1 and 2 list shRNA and guide RNA sequences targeting TCL1A, none of the disclosed examples demonstrate the utility of these inhibitors in treating hematologic malignancies, which is required by the instant claim language. No description is provided of a set of pharmacological agents, such as the small molecule drugs recited at instant claim 4, that inhibit TCL1A.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of identification of TCL1A as a factor underlying the clonal fitness advantage of several driver mutations in CHIP (paragraph [00187]), and the disclosure is only representative of shRNA and guide RNA sequences (Tables 1 and 2) theoretically capable of targeting TCL1A, as no in vitro or in vivo data is presented validating these reagents. Furthermore, no description is provided of any inhibition of TCL1A expression or activity, as is encompassed by the instant claim language. Given that the working examples of the instant specification are exclusively drawn to identification of TCL1A as a factor underlying the clonal fitness advantage of several driver mutations in CHIP (paragraph [00187]), the skilled artisan would not be able, based on the instant disclosure, to predict inhibitors targeting TCL1A expression or activity for purposes of treating hematologic malignancies, nor would the skilled artisan be reasonably apprised of the effect of inhibiting TCL1A expression or activity (i.e. its impact on hematologic malignancies). Thus, it is impossible for one to extrapolate from the association examples described herein those agents that would necessarily meet the structural/functional characteristics of the rejected claims.
Regarding the disclosed shRNA and guide RNAs, shRNAs represent a class of RNA inhibitors. The prior art clearly indicates that, in general, significant variability exists with regard to the functionality of individual RNAi molecules targeting the same gene. In fact, it is recommended when designing shRNAs that at least two target sequence should be designed for each gene “to increase the likelihood that at least one sequence results in significant gene knockdown” (reviewed in Moore et al., 2010: see page 141, paragraph 2). Therefore, given the variability in shRNA efficacy, the mere disclosure of the structure of an shRNA does not convey its functionality in knocking down the targeted gene of interest (in the instant case, TCL1A).
Furthermore, regarding the disclosed guide RNAs, it is known that different guide RNAs exhibit varying knockout efficiency due to different on-target cutting efficiency and/or DNA repair outcome (reviewed in Ong et al., 2017: see page 1, paragraph 3 of Introduction). As set forth above regarding the disclosed shRNA species, while the instant disclosure identifies the structure of sgRNAs and guide RNAs targeting TCL1A, it is entirely silent as to their function in knocking down the targeted gene of interest (in the instant case, TCL1A), which is required by the instant claim set.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of agents, including small molecule drugs, defined solely by their ability to function to inhibit TCL1A expression or activity. In fact, as of the effective filing date of the instant application, TCL1A (synonymous with TCL1) inhibitors were yet to be discovered (reviewed in Paduano et al., 2018: abstract; page 5, column 2, paragraph 2). As reviewed in Paduano et al., 2018, TCL1 activity is difficult to chemically inhibit, as TCL1 does not exert clear and known enzymatic activity, and further only the homodimer is active and works as a co-activator of AKT and presumably all other partners thereof (see section “TCL1 AS A THERAPEUTIC TARGET”). Based on a search of the prior art, no specific pharmacological inhibiting agents of TCL1A (including small molecule drug inhibitors) were known in the art prior to the effective filing date of the instant application (reviewed in Paduano et al., 2018). While siRNAs targeting TCL1A were known in the art prior to the effective filing date of the instant application, these siRNAs have only been tested in vitro, as reviewed in Herling et al., 2008 (section “siRNA transfection experiments”; Figure 5)-not as functional therapeutic agents to treat an individual for hematologic malignancies, as instantly claimed.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1, 4, and 9-12.
Claim Rejections – 35 USC § 112(a) – Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(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.
Claims 1, 4, 7, and 9-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for administration of an effective dose of an siRNA that inhibits TCL1A expression, does not reasonably provide enablement for administration of any agent that inhibits the expression or activity of TCL1A. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: Claim 1, 4, 7, and 9-12 are drawn to a method for treating an individual for hematologic malignancies, including CHIP, to reduce clonal expansion, wherein said method comprises administering an effective dose of an agent that inhibits expression or activity of TCL1A. Dependent claim 4 limits said agents to small molecule drugs, while dependent claim 10 further recites combinatorial administration of additional agents or regimens useful in the treatment of hematologic malignancies. The nature of the invention is complex in that one must know how to make inhibits of undefined structure or of a particular class of molecules without a specific structure for use in the treatment of hematologic malignancies including acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, chronic myeloid leukemia, chronic myelomonocytic leukemia, and diffuse large B-cell lymphoma (as recited at dependent claim 11), as well as heart disease (as recited at dependent claim 12).
Dependent claims 11 and 12 further recite “wherein the treatment provides for a reduction in the development of” several diseases. As set forth above (see section Claim Interpretation), under broadest reasonable interpretation, this limitation has been interpreted to recite the prevention of various diseases. The instant specification does not offer any clarifying definition of “reduction in development” and in fact explicitly discloses the prevention of diseases at paragraphs [0058] and [0059]. Therefore, the nature of the invention is further complex in that one must know how to prevent hematologic cancers (recited at dependent claim 11), as well as heart disease (as recited at dependent claim 12) by inhibiting TCL1A expression or activity.
Breadth of the claims: The claims broadly encompass the administration of compositions defined solely or primarily by function, wherein the compositions must be effective to inhibit TCL1A expression or activity to treat hematologic malignancies including acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, chronic myeloid leukemia, chronic myelomonocytic leukemia, and diffuse large B-cell lymphoma, as well as heart disease.
Dependent claim 11 and 12 further encompass the prevention of hematologic cancers (recited at dependent claim 11), as well as heart disease (as recited at dependent claim 12) by inhibiting TCL1A expression or activity.
The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the specification and existence of working examples: The instant specification envisions that the TCL1A molecular pathways identified therein will inform diagnostic and therapeutic efforts for CHIP, as well as that pharmacological inhibition of TCL1A may suppress growth of CHIP and hematological cancers associated with mutations in TCL1A and other implicated genes (paragraphs [00160] and [00185]), the working examples do not offer any evidence of TCL1A inhibitions and the therapeutics effects thereof. Further assertions that down-regulating TCL1A can prevent clonal expansion (paragraph [0096]) are supported by neither the instant disclosure nor the prior art. In the absence of any in vitro or in vivo data, these speculative conclusions merely constitute theoretical therapeutic framework requiring substantial experimental effort to fully realize, as set forth in greater detail below. As clearly stated in Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001: “Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.’) Tossing out the mere germ of an idea does not constitute an enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Applicant cannot rely on the knowledge of one skilled in the art to supply information on the novel aspects of the claimed invention, to which the instantly filed disclosure is largely silent, as set forth above.
Additionally, no description is provided of the treatment or prevention of hematologic cancers or of heart disease.
Predictability and state of the art: While the instant specification envisions treatment of CHIP and hematological cancers with TCL1A inhibiting agents such as shRNAs or sgRNAs (Tables 1 and 2), it is silent as to actual experimentation with said inhibiting agents as well as to in vivo translation of these therapeutic agents. The instant claim set broadly encompasses in vivo treatment of human subjects with said shRNAs or sgRNAs (among other inhibiting agents). However, as is known to those of ordinary skill in the art, applying CRISPR editing to patients in vivo is an underdeveloped and unpredictable topic in the current state of the art. As reviewed in Behr et al., 2021 and Liu et al., 2021 (while the cited art post-dates the earliest effective filing date of the instant application, these references are merely applied for evidentiary purposes to establish the state of the art), there are numerous hurdles to overcome before in vivo CRISPR therapy is commonplace. These hurdles include, but are not limited to, editing efficiency (discussed in section “Editing efficiency” of Liu et al., 2021), effective delivery of the editing machinery (discussed in section 6 of Behr et al., 2021 and section “Delivering methods” of Liu et al., 2021), off-target effects (discussed in section “Off-target effects” of Liu et al., 2021), and immunogenicity (discussed in section “Immunogenicity” of Liu et al., 2021). The instant specification is silent as to any proposals to overcome any of the hurdles set forth above, which would be necessary to apply in vivo CRISPR/Cas9 editing to human subjects to inhibit TCL1A in order to treat an individual for hematologic malignancies, as encompassed by the instant claim set.
Additionally, the instant claim set broadly encompasses treatment of CHIP and hematological cancers with TCL1A inhibiting agents, which constitute a staggering breadth of diseases and conditions to be treated by the instantly claimed method. Taking acute myeloid leukemia (AML; recited at dependent claim 11) as an example, AML is known to be a highly heterogenous disease involving multiple molecular mechanisms, meaning monitoring of multiple implicated genes (i.e. biomarkers) rather than of a single implicated gene is most useful for diagnosis, prognosis, and treatment from a clinical perspective (reviewed in Prada-Arismendy et al., 2016; see section “Conclusions”). Other hematologic cancers, such as those recited at dependent claim 11, develop by other mechanisms and pathways, with no indication in the art that a single target (such as TCL1A) is capable of treating all hematologic malignancies/cancers. In fact, while TCL1A is envisioned as a therapeutic target in the prior art, such therapeutic targeting was unrealized as of the effective filing date of the instant application (reviewed in Paduano et al., 2018). While Herling et al., 2008 discloses siRNAs targeting TCL1A were known in the art prior to the effective filing date of the instant application, these siRNAs have only been tested in vitro, as reviewed in Herling et al., 2008 (section “siRNA transfection experiments”; Figure 5)-not as functional therapeutic agents to treat an individual for hematologic malignancies, as instantly claimed. Nonetheless, the disclosure of Herling et al., 2008 provides enablement for the administration of an effective dose of an siRNA agent that inhibits expression of TCL1A, as per the instantly claimed method.
Furthermore, as set forth above, dependent claims 11 and 12 are drawn to the prevention of hematologic cancers and of heart disease. Looking to the prior art for guidance, a search of the prior art did not identify any methods which utilized TCL1A inhibiting agents to effectively prevent hematologic cancers or heart disease in a subject. In fact, no prior art was identified which taught effective prevention of hematologic cancers or heart disease using any agent similar to the agents recited in the instant claims or envisioned by the instant specification. The specification also does not provide any working example demonstrating prevention of hematologic cancers or heart disease in a subject. Therefore, given the lack of knowledge present in the prior art and the lack of guidance provided in the specification with respect to preventing hematologic cancers or heart disease, further experimentation would be required. Considering that the additional experimentation would require de novo experimentation without a guarantee of success, and further considering that any positive results (i.e., successful prevention of hematologic cancers or heart disease by TCL1A inhibition in a subject) would amount to a significant advancement in the state of the art, the additional experimentation required is considered undue, as set forth in greater detail below.
Finally, as set forth above, regarding the disclosed shRNA and guide RNAs, shRNAs represent a class of RNA inhibitors. The prior art clearly indicates that, in general, significant variability exists with regard to the functionality of individual RNAi molecules targeting the same gene. In fact, it is recommended when designing shRNAs that at least two target sequence should be designed for each gene “to increase the likelihood that at least one sequence results in significant gene knockdown” (reviewed in Moore et al., 2010: see page 141, paragraph 2). Given the variability in shRNA efficacy, one of ordinary skill in the art would be required to individually test each and every shRNA in order to determine whether it significantly inhibits TCL1A expression. Furthermore, regarding the disclosed guide RNAs, it is known that different guide RNAs exhibit varying knockout efficiency due to different on-target cutting efficiency and/or DNA repair outcome (reviewed in Ong et al., 2017: see page 1, paragraph 3 of Introduction). Accordingly, one of ordinary skill in the art would also be required to individually test each and every guide RNA in order to determine whether it significantly inhibits TCL1A expression. Essentially, while the instant disclosure identifies the structure of sgRNAs and guide RNAs targeting TCL1A, it is entirely silent as to their function, which is required by the instant claim set.
Amount of experimentation necessary: The quantity of experimentation needed to carry out the full scope of the claimed method is large. One could not rely upon guidance provided in the instant disclosure or prior art. In addition to the experimentation required to validate the reagents disclosed at Tables 1 and 2, one would also have to develop small molecule drugs and other pharmacological agents targeting TCL1A in order to practice the full scope of the instantly claimed method. Given that TCL1 inhibitors are yet to be discovered (reviewed in Paduano et al., 2018: see page 5, column 2, paragraph 2), this would require a large amount of inventive effort to design, synthesize, validate, and clinically test such inhibitors, including shRNAs and guide RNAs, as set forth above. The instant specification provides no guidance for doing so. Furthermore, the instant specification provides no guidance for the treatment of prevention of hematologic malignancies, as is encompassed by the instant claim set.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 1, 4, 7, and 9-12 are not considered to be fully enabled by the instant disclosure.
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.
Claims 1, 4, 7, 9-12 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.
Instant claim 1, from which all other claims directly or indirectly depend, recites “a method for treating an individual for hematologic malignancies, including clonal hematopoiesis of indeterminate potential (CHIP), to reduce clonal expansion, the method comprising: administering an effective dose of an agent that inhibits expression or activity of TCL1A.” It is thus unclear whether this recitation is drawn to an intended use of a method of treating an individual for hematologic malignancies, a method for treating an individual for CHIP, or a method to reduce clonal expansion. As is known to those of ordinary skill in the art, CHIP is not a hematologic malignancy. The instant specification discloses at paragraphs [0037] and [0040] that CHIP defines patients who have detectable somatic clonal mutations but who lack a known hematologic malignancy or other clonal disorder, meaning CHIP includes cells that have expanded but do not yet have a malignant phenotype. This is supported by the prior art, which discloses that CHIP is a malignant precursor but is not itself malignant (reviewed in Steensma, 2018). Therefore, a method for treating hematologic malignancies cannot be considered to read on treating CHIP, as instantly claimed, thereby rendering the intended use of the claim indefinite.
Furthermore, the instant claim language may also be interpreted as a method of reducing clonal expansion. It is not clear from the instant claim language whether reducing clonal expansion is a separate embodiment of the instantly claimed method or whether reducing clonal expansion is for purposes of treating an individual for hematologic malignancies. Therefore, the intended use is unclear and indefinite.
The intended use of the instant claim set is further obscured by the recitation of dependent claim 12, which recites “the treatment [of the method of claim 1] provides for a reduction in the development of heart disease.” As is known to those of ordinary skill in the art, heart disease is also not a hematologic malignancy. This is supported by the instant specification, which discloses that the term “hematological malignancy” refers to all stages and all forms of cancer arising from cells of the hematopoietic system (paragraph [0041]), such as those disclosed at paragraph [0042], which do not include heart disease. Therefore, a method for treating hematologic malignancies cannot be considered to read on treating heart disease, as instantly claimed, thereby rendering the intended use of the claim indefinite.
While dependent claim 11 does recite treatment providing for a reduction in the development of hematologic cancers, which do read on the instantly claimed hematologic malignancies as per paragraph [0041] of the instant specification, dependent claims inherit all the limitations of the independent claim from which they depend. Therefore, dependent claim 11 also encompasses treatment of CHIP, which is not a malignant condition, as set forth above.
It would be remedial to amend the instant claim set to clearly recite what condition(s) are treated by the methods claimed therein such that the metes and bounds of protection sought by the instant claim set are clear to those of ordinary skill in the art.
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.
Claims 1, 7, 9, 11, and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Herling et al., 2008 (hereinafter Herling).
With regard to claim 1, which recites “a method for treating an individual for hematologic malignancies, including clonal hematopoiesis of indeterminate potential (CHIP), to reduce clonal expansion, the method comprising: administering an effective dose of an agent that inhibits expression or activity of TCL1A,” as set forth above (see section Claim Interpretation), the only method step recited at instant claim 1 is “administering an effective dose of an agent that inhibits expression or activity of TCL1A.” While the preamble of instant claim 1 is drawn to treatment of various hematologic conditions, the preamble is drawn to intended use and is therefore not given patentable weight (see MPEP § 2111.02(II)). Therefore, any art disclosing administration of an effective dose of an agent that inhibits expression or activity of TCL1A must read on the instantly claimed method. Herling discloses transient knockdown of TCL1 with siRNAs targeting TCL1, thereby reducing expression of the same (Figure 5B; page 335, column 1, paragraph 2). Accordingly, Herling discloses administration of an effective dose of an agent that inhibits expression or activity of TCL1A and therefore reads on the instantly claimed method, thereby anticipating each and every limitation of instant claim 1.
With regard to claim 7, which recites “the method of claim 1, wherein the individual is genotyped prior to treatment,” as set forth above, the only method step recited at instant claim 1 is “administering an effective dose of an agent that inhibits expression or activity of TCL1A.” Therefore, any genotyping prior to treatment does not further limit the claimed active step of administration of an effective dose of an agent that inhibits expression or activity of TCL1A. Thus, it is considered that Herling discloses each and every limitation of instant claim 7.
With regard to claim 9, which recites “the method of claim 7, wherein the genotyping determines the presence of driver mutations in one or more of TET2, ASXL1, SF3B1, SRSF2, TP53, JAK2, PPM1D, NRAS, KRAS, IDH1, and IDH2 prior to treatment, and found to have at least one driver mutation, as set forth above, the only method step recited at instant claim 1 is “administering an effective dose of an agent that inhibits expression or activity of TCL1A.” Therefore, any genotyping prior to treatment does not further limit the claimed active step of administration of an effective dose of an agent that inhibits expression or activity of TCL1A. Thus, it is considered that Herling discloses each and every limitation of instant claim 9.
With regard to claim 11, which recites “the method of claim 1, wherein the treatment provides for a reduction in the development of hematologic cancers, including without limitation acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, chronic myeloid leukemia, chronic myelomonocytic leukemia, and diffuse large B-cell lymphoma,” as set forth above, the only method step recited at instant claim 1 is “administering an effective dose of an agent that inhibits expression or activity of TCL1A.” Therefore, treatment of any particular hematologic malignancy does not further limit the claimed active step of administration of an effective dose of an agent that inhibits expression or activity of TCL1A. Thus, it is considered that Herling discloses each and every limitation of instant claim 11.
With regard to claim 12, which recites “the method of claim 1, wherein the treatment provides for a reduction in the development of heart disease,” as set forth above, the only method step recited at instant claim 1 is “administering an effective dose of an agent that inhibits expression or activity of TCL1A.” Therefore, treatment of any particular hematologic condition does not further limit the claimed active step of administration of an effective dose of an agent that inhibits expression or activity of TCL1A. Thus, it is considered that Herling discloses each and every limitation of instant claim 12.
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.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Herling et al., 2008 (hereinafter Herling) as applied to claim 1 above, and further in view of Paduano et al., 2018 (hereinafter Paduano) and Mokhtari et al., 2017 (hereinafter Mokhtari).
The disclosure of Herling is described above and applied as before (see section Claim Rejections - 35 USC § 102). However, this disclosure does not teach the combination therapy of instant claim 10.
With regard to claim 10, which recites “the method of claim 1, wherein the treatment is combined with administration of additional agents or regimens useful in the treatment of hematologic malignancies,” as set forth above, Herling discloses transient knockdown of TCL1 with siRNAs targeting TCL1, thereby reducing expression of the same (Figure 5B; page 335, column 1, paragraph 2). However, Herling does not disclose administration of said siRNAs in the context of cancer treatment-combination or otherwise. This deficiency is cured by Paduano and Mokhtari.
Paduano discloses that TCL1 (or TCL1A) is an emerging new target for anticancer therapy, particularly in hematologic malignancies (abstract; page 4, column 2, paragraph 2). Furthermore, Mokhtari discloses that combination therapy (a treatment modality that combines two or more therapeutic agents) is a cornerstone of cancer therapy (abstract). Per Mokhtari, combination therapy has provided the most effective results with regard to anti-cancer effects due to its ability to target multiple pathways, thereby minimizing drug resistance (page 38034, column 2, paragraph 3).
Given that Herling discloses siRNAs targeting TCL1A, that Paduano discloses that TCL1 (or TCL1A) is an emerging new target for anticancer therapy, particularly in hematologic malignances, and that Mokhtari discloses that combination therapy is the most effective treatment against cancer, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to apply the siRNAs disclosed in Herling to the inhibition of TCL1A (as disclosed in Paduano) in combination with another useful therapeutic agent against hematologic malignancy (as disclosed in Mokhtari) to predictably treat cancers such as hematologic malignancies. One would have been motivated to make such a modification in order to receive the expected benefit of treating cancers such as hematologic malignancies.
Conclusion
No claims are allowed.
Claim 9 is objected to.
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/SARAH E ALLEN/Examiner, Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637
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