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 .
DETAILED ACTION
Claims 1, 3-6, 12, 20, 22, 27-29, 31-33, 35-37, 39-40, and 42-43 are pending in the instant application.
Claims 1, 3-6, 12, 20, 22, 27-29, 31-33, 35-37, 39-40, and 42-43 are examined herein.
Priority
The instant application claims benefit of priority to U.S. Provisional Application No. 63/252,298, filed on 05 October 2021, and PCT/US2022/045822, filed on 05 October 2022. The claims to the benefit of priority are acknowledged. As such, the effective filing date of the claims is 05 October 2021.
Information Disclosure Statement
No information disclosure statement (IDS) submitted by applicant.
Claim Interpretation
Claims 37 and 43 are directed to a composition; as such, the intended use (i.e. for treating cancer) does not alter the chemical structure(s) of composition and is therefore not further limiting. See MPEP 2111.02.II:
[S]tatements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim. See, e.g., In re Otto, 312 F.2d 937, 938, 136 USPQ 458, 459 (CCPA 1963) (The claims were directed to a core member for hair curlers and a process of making a core member for hair curlers. The court held that the intended use of hair curling was of no significance to the structure and process of making.); In re Sinex, 309 F.2d 488, 492, 135 USPQ 302, 305 (CCPA 1962) (statement of intended use in an apparatus claim did not distinguish over the prior art apparatus). To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997) (anticipation rejection affirmed based on Board’s factual finding that the reference dispenser (a spout disclosed as useful for purposes such as dispensing oil from an oil can) would be capable of dispensing popcorn in the manner set forth in appellant’s claim 1 (a dispensing top for dispensing popcorn in a specified manner)) and cases cited therein.
Claim 5 recites the relative term “about,” this is clearly defined in paragraph [00037] of the specification.
Regarding claim 1 and 3, claim 1 establishes the functional limitation of treating cancer with a SERD in an amount sufficient to increase the effectiveness of an ICB therapy. This functional limitation would require the patient to be on an existing ICB therapy. Therefore claim 3 is interpreted to be administration of the ICB therapy in addition to that of claim 1.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located on pages 79-81. Only SEQ ID NO 1 is disclosed in the “Sequence Listing” file.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
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.
Claims 1, 3-6, 12, 20, 22, 27-29, 31-33, 35-37, and 42-43 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 the treatment of melanoma fails to provide the required enablement for the treatment of all cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The instant claims are drawn to a method of treating cancer comprising administering a selective estrogen degrader (SERD) to increase the effectiveness of an immune checkpoint blockade (ICB) therapy. The specification fails to provide information that would allow the one skilled in the art to practice treating all cancer.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
the nature of the invention
the state of the prior art
the predictability of the art
the amount of direction or guidance provided
the presence or absence of working examples
the breadth of the claims
the quantity of experimentation necessary
the relative skill of those in the art
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention - is a method of treating cancer comprising administering a SERD capable of increasing the effectiveness of an ICB therapy.
The state of the prior art - the pharmacological art requires the screening of potential drug candidates in vitro and in vivo to determine if the drug candidates exhibit the desired pharmacological activities.
In order to treat a disease: one would need to precisely identify what the disease is, identify what biological target is connected with the disease, demonstrate that the drug candidate in some way modulates the normal processes of the biological target, and demonstrate that a patient benefited from such modification without detrimental side effects. Typically, this process includes in vitro laboratory screening, preclinical in vivo screening, and three phases of clinical trials. Once this arduous process has been successfully completed by a drug candidate, subsequent drug candidates will benefit from the established proof of concept. The subsequent drug candidates must demonstrate a substantial correlation between their biological activity and that of the known drug candidate.
In the instant case, the prior arts recognize that therapeutic agents have potential to exhibit antagonistic property toward the estrogen receptor, which can be used to treat breast cancer (Xiong et al. J. Med. Chem. 2017; 60: 1325−1342).
The predictability or unpredictability of the art – the law recognizes the pharmaceutical art as an unpredictable art and requires each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 24 (CCPA 1970). Accordingly, the more unpredictable an area is the more specific disclosure is necessary in order to satisfy the statute. Section 2164.02 of the MPEP provides:
"[C]orrelation” as used herein refers to the relationship between in vitro and in vivo animal model assays and a disclosed or a claimed method of use . . . if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate.
In light of these remarks, the Examiner finds that one of ordinary skill in the art would agree with the court; that is, the pharmaceutical art is unpredictable. Thus, a substantial correlation is necessary for establishing the potential of new therapeutics.
Additionally, within pharmaceutics, the art of cancer therapeutics is well known to be unpredictable due to the differing etiologies and mechanisms of action for particular cancers. There are more than 200 known cancers; treatment applicable to one is unlikely to be applicable to another. Bianchi et al. (Current Opinion in Cell Biology. 2020; 63:135-143) attributes this unpredictability to tissue specificity, noting most cancer driver genes are mutated in a tissue-dependent manner, which affects therapeutic response (page 135). For example, BRAF inhibition is an effective therapy for BRAF-mutated melanomas, but not BRAF-mutated colon cancer (page 140); same mutation, different tumors, therefore different therapeutic outcomes. Therefore, from the well-established state of cancer arts, a skilled practitioner would not conclude all cancers could be treated, managed or improved with the same therapeutic agent.
The amount of direction or guidance presented – the instant specification provides an explanation of the biological activity of ER on page 2, and discusses the implication of estrogen inhibitors in the treatment of melanoma. There is no direction or guidance provided that supports a use of a SERD in the treatment of all cancers.
The amount of guidance or direction to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. MPEP § 2164.03 (quoting In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 24 (CCPA 1970)). As identified supra, the pharmaceutical art is recognized as unpredictable.
Thus, in order to support a claim for treating all cancer disease a vast amount of evidence is required because such a claim is not supported by the prior art or the instant specification.
The presence or absence of working examples - there are no working or prophetic examples in the specification that demonstrate that the instant compounds or compositions thereof may treat all cancer. The assays in the specification demonstrate that the instant compounds were tested for their ability to reduce tumor growth in three melanoma cell lines (Example 7, page 63).
The breadth of the claims – is incommensurate in scope with the disclosure because a fair reading of the specification fails to support a finding that the compositions of claim 1 would be able to treat any cancer in a patient.
The quantity of experimentation necessary – generally speaking, the amount of experimentation to transform a molecule into medicine is vast and the success thereof is low. Recent statistics indicate that the attrition rates during drug development remain high. Schafer et al. Drug Discovery Today 2008, 13 (21/22), 913-916. The article makes clear that there are many steps necessary to promote a new molecular entity toward its clinical use, any one of which is cumbersome.
For instance, Schafer et al. discloses: "proof of concept trials have failed when the decision to enter clinical development was based on preclinical experiments using the wrong compound, the wrong experimental model, or the wrong endpoint.” It can be gleaned from this article that a plethora of experimentation is needed to identify the lead compound (i.e. one among many in a Markush-type claim), to establish which preclinical tests are predictive of clinical success, and to establish which diseases are the best to target for each lead compound.
There is generally a vast amount of experimentation to take a drug from bench to the clinic. See e.g., Horig et al. Journal of Translational Medicine 2004, 2(44) (“Successful drug development requires satisfying a matrix of domains from relevance to the disease and the drug-ability of the target through feasibility and convenience of drug delivery, demonstration of favorable benefit-risk profile in order to achieve a drug label that reflects physician and patent acceptance.") The Examiner finds that one of ordinary skill in the art would agree with the statements in these articles; that is, the amount of experimentation required to enable a pharmaceutical drug is extensive.
The level of skill in the art - the level of ordinary skill in the art may be found by inquiring into: (1) the type of problems encountered in the art; (2) prior art solutions to those problems; (3) the rapidity with which innovations are made; (4) the sophistication of the technology; and (5) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of those factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983).
Based on the typical education level of the active workers in the field of pharmaceuticals and/or medicine, as well as the high degree of sophistication required to solve problems encountered in the art, the Examiner finds that a person of ordinary skill in the art would have at least a college degree in a field related to medicine and/or the pharmaceutical art and at least four years of work experience, i.e. a masters or doctorate level scientist/clinician.
Therefore, claims 1, 3-6, 12, 20, 22, 27-29, 31-33, 35-37, and 42-43 are rejected because the Examiner finds that the Wands factors suggest a conclusion that the skilled artisan would not be able to make and use the instant invention without undue experimentation, although the level of skill for an ordinary person in the art is high. That is, due to the breadth of the claims, the unpredictability of the art, the lack of guidance or direction from the disclosure, the lack of any working examples, and the amount of experimentation needed illustrate that a person having ordinary skill in the art would not be able to treat all cancer.
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.
Claims 1, 3-6, 12, 20, 22, 27-29, 31-33, 35-37, 39-40, and 42-43 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 is directed to a method of treating an individual with cancer comprising administering at least one SERD in an amount sufficient to increase the effectiveness of an ICB therapy. “Increasing the effectiveness of an ICB therapy” is a functional limitation which requires a compound to provide at least an additive therapeutic effect to an existing therapeutic treatment involving an ICB. This term does not describe an art-recognized genus of compounds and Applicant’s disclosure does not provide sufficient written description to support this functional limitation.
See MPEP 2163 II. A. 3. (a) (ii) with regards to the requirements for descriptive support and for functional limitations of generically described entities:
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”
“A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.”
There is no structure-function relationship for increased efficacy of an ICB therapy by administering a SERD in the prior art. The art teaches diverse structural features for SERDs, demonstrating they do not encompass just one structural genus. The SERDs recited in claim 1 also do not encompass one structural genus. Additionally, the art teaches success in combination therapies with SERDs at varying degrees.
Turner et al. (N Engl J Med 2018;379:1926-1936) report an increase in progression-free survival for breast cancer patients being administered the SERD, fulvestrant, and the CDK4/6 inhibitor, palbociclib. Bidard et al. (N Engl J Med. 2025 Aug 7;393(6):569-580) also report an increase in progression-free survival for the SERD, camizestrant, and palbociclib. Whereas it is reported that the combination of the SERD giredestrant and palbociclib offers no statistical improvement (Beaney. Clinical Trials Arena. 2026. https://www.clinicaltrialsarena.com/news/roches-oral-serd-fails-in-phase-iii-breast-cancer-trial/?cf-view). The art shows that the combination of two drug classes does not always produce an increase in therapeutic response.
The specification does not provide an adequate representation of species of the possible SERDs recited that can increase the effectiveness of an ICB therapy. Claim 1 provides 15 different SERDs, however the specification only demonstrates fulvestrant as meeting the functional limitation. Failure to represent the functional limitation with a representative number of species, and through relationship of structure and function, which would provide an overall depiction of the claimed subject matter, suggests the applicant is not in possession of the claimed invention.
To summarize, there is a lack of descriptive support since the claims recite a functional limitation and: (i) the provided species are not sufficiently representative of the genus of compounds having such function, (ii) multiple other species with the function are known in the art with completely different structural and variable mechanistic features and (iii) there is no general art-recognized structure-function relationship for compounds with the required functional activity.
Claims 6, 12, 20, 22, 28, 31-33 and 29 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 6 recites the method of claim 1 wherein the method further comprises administering to the subject at least one additional therapy. An “additional therapy” is a functional limitation which requires either a compound to treat or manage a disease, or a medical procedure to treat or manage a disease. This term encompasses a broad genus of compounds and procedures and the Applicant’s disclosure does not provide sufficient written description to support this functional limitation.
See MPEP 2163 II. A. 3. (a) (ii) with regards to the requirements for descriptive support and for functional limitations of generically described entities:
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”
“A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.”
There is no structure-function relationship provided in the specification to establish the limitations of the claim. The art does not recognize a general structure-function relationship for an “additional therapy.” An “additional therapy” encompasses a wide genus of compounds, without structural similarity or function, and procedures. Proper support of the claimed functional limitation requires a presented correlation between the structure of the additional therapeutic agent and the function of the additional therapeutic agent.
The specification does not provide an adequate representation of all the possible species of additional therapeutic agents, as recited by claim 6. Only considering therapeutic agents requiring a prescription, there is estimated to be over 20,000 available to patients in the United States (NCSL. 2022. https://www.ncsl.org/health/prescription-drugs-and-the-approval-process). The specification provides no examples of additional therapeutic agents or therapies administered in addition to a SERD and an ICB. Claim 12 further limits the additional therapeutic agents and therapies, however as no working examples are given, this is still not an adequate representation of the claim. Combination therapies are known to be a powerful tool in pharmaceutics, but they require testing. Sun et al. (Drug Discov Today. 2016 May 27;21(7):1189–1195.) discusses the potential for drug-drug interactions in combination therapies that can lead to adverse side effects, toxicities, and antagonism in which the drug(s) efficacy is diminished. With no working examples the applicant has not shown which additional therapeutics would work and which would not, as the skilled artisan would not believe all possible additional therapeutics would result in a efficacious combination. Failure to present a representative number of species of additional therapies, which would provide an overall depiction of the claimed subject matter, suggests the applicant is not in possession of the claimed invention.
To summarize, there is a lack of descriptive support since the claims recite a functional limitation and: (i) the provided species are not sufficiently representative of the genus of compounds having such function, (ii) multiple other species with the function are known in the art with completely different structural and variable mechanistic features and (iii) there is no general art-recognized structure-function relationship for compounds with the required functional activity.
Claim Rejections - 35 USC § 112
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 39-40 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.
Claim 39 references Table 5 of the specification which renders the claim indefinite as claims are to complete in themselves. See MPEP 2173.05(s). As dependent claim 40 does not remedy the issue it is also subject to the rejection.
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.
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, 12, 20, 22, 27-29, 31-33, 35-37, and 42-43 are rejected under 35 U.S.C. 103 as being unpatentable over Pietras et al. (US20220133747A1; EFD 06 June 2018) in view of Hoffman-La Roche (Clinical Trial NCT03280563; 2023 Study Protocol PDF made available to Applicant, 2017 Study Protocol available at https://clinicaltrials.gov/study/NCT03280563?term=NCT03280563&viewType=Card&rank=1&tab=history&a=1#version-content-panel. Note the study was made publicly available on 12 September 2017, this information is found under the Study Record Dates, and a snapshot has been made available below).
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Regarding claims 1, 3, and 42, Pietras discloses a method of treating a proliferative disorder comprising administering an effective amount of a checkpoint inhibitor and a compound of Formula (I). Formula (I) describes a genus of SERDs.
Pietras’ work is not focused on fulvestrant and an anti-PDL1 antibody; though this example is used to compare the efficacy of the combination of reference SERD128 (also known as JD128; CAS registry number 1934254-35-9) and an anti-PDL1 antibody to the combination of fulvestrant and an anti-PDL1 antibody(paragraph [0718]; Figures 25D-26B)
However, the use of fulvestrant and an anti-PDL1 antibody in the treatment of cancer was already under clinical investigation by Hoffman-La Roche.
It would be prima facie obvious to one of ordinary skill in the art to combine a SERD, particularly fulvestrant, and an ICB therapy in the treatment of cancer. Pietras demonstrated the efficacy of SERD128 and an ICB therapy, as well as the efficacy of fulvestrant and an ICB therapy. Though the efficacy of SERD128 is higher the skilled artisan would be guided to using fulvestrant and an ICB therapy as fulvestrant is an established and widely-used SERD, while SERD128 is still undergoing clinical investigation as a monotherapy. Additionally, Hoffman-La Roche was investigating the clinical efficacy of a combination of fulvestrant and the ICB therapy anti-PD-L1 drug atezolizumab. Therefor the combination of fulvestrant and an anti-PDL1 antibody was known in the art and substitution of fulvestrant for SERD128 taught by Pietras would be obvious.
Regarding claim 4, Pietras and Hoffman-La Roche teach anti-PDL1 antibodies.
Regarding claim 5, both Pietras and Hoffman-La Roche teach the method of administering fulvestrant and an anti-PDL1 antibody to cancer patients. As the prior art teaches administering the claimed compound to the claimed patient population, in an effective amount it would appear that the claimed limitation of increasing the effectiveness of the ICB therapy does necessarily occurs. MPEP 2112.01:I states:
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.”
Regarding claim 6, Pietras teaches administering an additional agent (paragraph [0327]). Also, Hoffman-La Roche teaches additionally administering ipatasertib with the combination of fulvestrant and atezolizumab,
Regarding claim 12, Pietras defines the additional agent can be chemotherapeutic (paragraph [0135]). And Hoffman-La Roche teach a chemotherapeutic.
Regarding claim 20, Pietras teaches the additional agent can be an anti-cancer agent which includes alkylating agent, anti-metabolites and a topoisomerase inhibitor (paragraph [0136]).
Regarding claim 22, Pietras teaches the additional agent can be entinostat (paragraph [0346]).
Regarding claims 27 and 29, Pietras teaches co-administration is simultaneous or sequential (paragraph [0155]).
Regarding claim 28, Pietras teaches the additional agent can be vemurafenib (paragraph [1036]).
Regarding claim 31, Hoffman-La Roche teaches the administration of fulvestrant once every two weeks.
Regarding claim 32, Hoffman-La Roche teaches the treatment for up to 6 years.
Regarding claim 33, Pietras teaches the oral, intravenous, transdermal or vaginal administration of the SERD (paragraph [0154]).
Regarding claim 35, Pietras teaches the method of treating cancer wherein the cancer is melanoma, colon cancer, breast cancer or lung cancer (paragraph [0141]). Additionally Hoffman-La Roche teaches the method for breast cancer.
Regarding claim 36, Pietras shows increased proliferation of CD8+ T cells in tumors in mice treated with fulvestrant and an anti-PDL1 antibody, (Figure 25D).
Regarding claims 37, Pietras teaches the composition comprising both a SERD and an anti-PDL1 antibody (paragraph [0163]).
Regarding claim 43, Pietras teaches the composition comprising both a SERD and an anti-PDL1 antibody (paragraph [0163]), Pietras also discloses the composition may comprise tamoxifen, a SERM (paragraph [0327]).
Conclusion
Claims 1, 3-6, 12, 20, 22, 27-29, 31-33, 35-37, 39-40, and 42-43 are rejected.
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/J.K.W./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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