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 .
Priority
The instant application is a 35 U.S.C. 371 national phase application and claims priority to International Application No. PCT/US2022/077679 (filing date 10/06/2022), which claims the benefit of the prior-filed United States Provisional Patent Application No. 63/252,568, filing date 10/06/2021.
Status of Application/Claims
The preliminary amendment, filed 11/04/2024, is acknowledged. Claims 1-39 are canceled. Claims 40-59 are new. Claims 40-59 are currently pending and are examined on the merits herein.
Information Disclosure Statements
No IDS was filed by applicant.
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 fails to comply with the requirements of 37 CFR 1.821 - 1.825 because the "Sequence Listing" part of the disclosure submitted as a PDF file (37 CFR 1.821(c)(2)) or on physical sheets of paper (37 CFR 1.821(c)(3)) is not the same as the CRF of the "Sequence Listing" as required by 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii). The SEQ ID NO: 20, as it appears on p.100 of the disclosure, appears to be correct compared to the “Sequence Listing (XML File)” filed 04/05/2024 which contains a string of “SEQSEQSEQS” at the C-terminal end of SEQ ID NO: 20.
Required response - Applicant must provide:
A replacement "Sequence Listing" as described above in items 1) c) or d) in accordance with 37 CFR 1.825(b)(1)(ii) or (iii); as well as
An amendment specifically directing its entry into the application as required by 37 CFR 1.825(b)(2)(ii);
A statement that identified the locations of any deletions, replacements or additions to the “Sequence Listing” as required by 37 CFR 1.825(b)(3);
A statement that the "Sequence Listing" added by amendment includes no new matter as required by 37 CFR 1.825(b)(5);
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4); and
A statement that the content of the previously-filed CRF is identical to the "Sequence Listing" part of the disclosure added by amendment as required by 37 CFR 1.825(b)(7), where provided under item 1) c) or d) (note that where a "Sequence Listing" part of the disclosure is provided under item 1) a) or b), the text file will also serve as the CRF, and the statement of identity is not required);
OR
A CRF as required by 37 CFR 1.821(e)(1) or 1.821(e)(2); and
A statement that the content of the CRF is identical to the "Sequence Listing" part of the disclosure previously submitted as a PDF file (37 CFR 1.821(c)(2)) or on physical sheets of paper (37 CFR 1.821(c)(3)), as required by 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii).
Specification
The use of the terms Biacore, Pharmacia, Biosensor, Affinity, Windsor, Nippon, Texas Instruments, Calbiochem, Avanti, Inovio, and Ablynx, which are trade names or marks used in commerce, have been noted in this application. The terms should be in all caps wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 41 is 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 41 recites dependency on claim 1 which has been canceled. Thus, claim 41 is rendered indefinite. For further examination, claim 41 is interpreted to be dependent on instant claim 40 as the content of instant claim 40 is identical to canceled claim 1.
Claim Rejections - 35 USC § 112(a)
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 46-47 and 56-57 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 cancer, does not reasonably provide enablement for the prevention of 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.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). The court in Wands states: “Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue,’ not ‘experimentation.’” (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: The nature of the invention; the breadth of the claims; the amount of direction provided by the inventor; the existence of working examples; the state of the prior art; the level of predictability in the art; the quantity of experimentation needed to make or use the invention based on the content of the disclosure; and, the level of one of ordinary skill. While all of these factors are considered, a sufficient amount for amount for a prima facie case are discussed below.
The nature of the invention
Claims 46 and 47 are drawn to a method of preventing a disease or disorder, and wherein the disorder is cancer, respectively, by administering the nucleic acid molecule of claim 40.
Claims 56 and 57 are drawn to a method of preventing a disease or disorder, and wherein the disorder is cancer, respectively, by administering the NKE of claim 50.
The breadth of the claims
The claims are broad in that they encompass the prevention of any cancer.
The claims are broad and inclusive of all types of cancer. The breadth of the claims exacerbates the complex nature of the subject matter to which the present claims are directed. Cancer is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands. They can occur in pretty much every part of the body. For example, there are solid cancers of the brain, spine, live, prostate, testes, ovaries, bile duct, blood vessels, lung and pleural cavity, thyroid, skin (including melanoma), colon, prostate, kidneys, breasts, testicles, vulva and vagina, uterus, cervix, fallopian tubes, thymus, stomach, esophagus, spleen, salivary glands, heart, oral cavity, adrenal glands, eye, head and neck, bladder, bone, and gall bladder. Each of these types of cancer have potentially dozens of sub-categories that each have unique physiological and etiological characteristics.
The amount or direction provided by the inventor/ the existence of working examples
The examples of the instant disclosure studied the cytotoxic effect treatment in serous ovarian OVCAR4, BRCA2, Kuramochi cancer cells (p.88-89; Figs.2 and 4-5).
The examples provided do not demonstrate the prevention of recurrence of cancer. Additionally, the disclosure does not discuss, or demonstrate through working examples, a method that could be used to determine that cancer was prevented using the claimed agents as there is no disclosed method to determine that cancer would have predictably occurred without treatment.
The state of the prior art/ the level of predictability in the art
There are no art recognized methods that could be used to establish that the cancer was prevented using the claimed therapeutic method. Additionally, there are no art recognized methods that could be used to identify subjects who would have predictably developed cancer in order to determine that the cancer was prevented using the claimed methods.
Regarding biomarkers (and immunotherapies) in cancer, McKean et al. Biomarkers in precision cancer immunotherapy: Promise and challenges. American Society of Clinical Oncology – Educational Book (2020), 40, p.e275-e291 (herein referred to as McKean) teach that although ongoing studies and trials investigate the use of multiple biomarkers predictive of patient response or harm, none of these are comprehensive in predicting potential benefit (of treatment). This unmet need for validated biomarkers is largely secondary to a prohibitive complexity within tumor parenchyma and microenvironment, dynamic clonal and proteomic changes to therapy, heterogenous host immune defects, and varied standardization among sample preparation and reporting (abstract). McKean also teach that treatment failures occur even in ICI patient cohorts, despite respective prescreening with biomarkers such as PD-L1 tumor proportion scores (p.e275). Regarding gene expression profiles specifically, McKean teaches that an important concept within gene expression profiles is that the predictive utility of such algorithms may be dependent on individual therapy plans. Data suggest that signaling and transcriptomic patterns may correlate only with response to therapy of directly related targets (p.e280). Unrelated immune pathways may require separate and individualized gene expression assays for different therapies (p.e280). Therefore, the selection of a particular therapy for any specific type of cancer is unpredictable, and requires individualized assays that are fully described to achieve correlation.
Ahmadzada et al. An update on predictive biomarkers for treatment selection in non-small cell lung cancer. Journal of Clinical Medicine (2018), 7:153, p.1-12 (herein referred to as Ahmadzada) also suggest that it is still difficult to apply classification of cancers to select targeted therapies. For example, Ahmadzada teaches that non-small cell lung cancer is a highly heterogeneous disease that develops from genetic mutations and gene expression patterns that initiate uncontrolled cellular growth, proliferation, and progression (p.2). Ahmadzada also teaches that only 15-25% of non-small cell lung cancer patients benefit from immunotherapy, suggesting the need for novel biomarkers to identify the best candidates for treatments (p.7). Further, Ahhmadzada et al. also recognize that the heterogeneity of NSCLC remains a key barrier to accurate molecular classification and necessitates individualization of treatment (p.8)
The American Cancer Society maintains that “There's no sure way to prevent cancer, but you can help reduce your risk by making healthy choices like eating right, staying active, and not smoking” (American Cancer Society. Cancer Risk and Prevention. 1/1/2025. Internet – Wayback Machine. p.1-4).
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
Studies regarding treatment and prevention of cancer are underway that aim to improve earlier detection and better treatments for cancer. However, based on the disclosure and the prior art, there is no known or disclosed method through which an ordinarily skilled artisan would have been able to predictably identify subjects who would have predictably developed cancer in order to determine that the cancer were prevented using the claimed methods. Therefore, in order to practice the invention as claimed, an ordinarily skilled artisan would have to participate in undue experimentation to determine a method that would allow for the prevention of recurrence of cancer.
In view of the Wands factors discussed above, a person of ordinary skill in the art would have to engage in undue experimentation to practice the full scope of the claimed invention. As such, instant claims 46-47 and 56-57 were determined to not meet the scope of enablement requirement of 35 U.S.C. 112(a).
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 40-42, 45-52, 55-59 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Bigelow, et al.—WO2019195409A1 (publication date: 10/10/2019; effective filing date: 04/03/2018; herein referred to as Bigelow).
Bigelow teaches proteins binding NKG2D, CD15 and an antigen associated with tumors, myeloid-derived suppressor cells (MDSCs), and/or tumor-associated macrophages (TAMs); and, compositions and therapeutic treatments for cancer thereof (title; abstract). Bigelow teaches that NK cells respond to signals through a variety of activating and inhibitory receptors on their surface; and when NK cells encounter foreign cells or cancer cells, they are activated via their activating receptors including NHG2D, natural cytotoxicity receptors (NCRs), DNAX accessory molecule 1 (DNAM1) ([0007]). Bigelow teaches that NK cells are also activated via CD16 receptors on their cell surface {0007]). Bigelow teaches that a variety of antigens may be expressed in the tumor microenvironment ([0026]). Bigelow teaches “multi-specific binding proteins” that bind NKG2D, CD16, and cancer cell proteins, including specific embodiments wherein a first antigen-binding site binds NKG2D and a second antigen-binding site that binds a tumor-associated antigen that is Siglec-9 (i.e., a sialic acid-binding receptor on a target tumor cell; [0028]; [0175]; claims 45, 66). Bigelow teaches that the multi-specific binding proteins can be antibodies or fragments thereof, wherein recombinant DNA technology can be used to express the immunoglobulin chains in host cells ([0292]; claim 98). Thus, Bigelow teaches nucleic acid molecules comprising nucleotide sequences that encode for the instantly claimed “natural killer engager (NKE).” Bigelow further teaches a method of treating cancer by administering the multi-specific protein (claim 100). Bigelow also teaches a method of directly and/or indirectly enhancing tumor cell death comprising exposing a tumor microenvironment and NK cells to the protein (i.e., increasing NK cell function toward a tumor; claim 99).
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 45 and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Bigelow, et al.—WO2019195409A1 (publication date: 10/10/2019; effective filing date: 04/03/2018; herein referred to as Bigelow) as applied to claims 40 and 50 above; and, further in view of additional teachings by Bigelow.
Bigelow teaches A nucleic acid that encodes for an NK engager that binds to a sialic acid-binding receptor binding antibody linked to a target cell binding antibody, and compositions thereof, as applied to claims 40, 45, 50, and 55 above.
Bigelow does not expressly teach a specific embodiment for a composition that comprises the nucleic acid or NK cell engager and a pharmaceutically acceptable excipient (instant claims 45-b and 55-b, respectively); or, a composition comprising the NK engager and a cell expressing a chimeric antigen receptor comprising the NK engager (instant claim 55-d).
Bigelow additionally teaches combination therapies, therapeutic applications, and pharmaceutical compositions that comprise an effective amount of the NK engager (p.139-149) wherein the pharmaceutical composition can comprise physiologically acceptable excipients or carriers for proper formulation prior to administration to subjects for therapeutic treatment ([0321]).
It would have been prima facie obvious for one of ordinary skill before the effective filing date of the claimed invention to combine the teachings of Bigelow by comprising the NK engager or nucleotide sequence thereof in a pharmaceutical composition that also comprises a physiologically acceptable excipient in order to arrive at the instantly claimed invention because the combination of prior art teachings teaches that excipients can be added to the formulation for the benefit of producing a physiologically acceptable formulation prior to administration for treatment.
Bigelow further teaches that NKG2D can be fused to nucleic acid sequences encoding a CD3 zeta signaling domain to obtain chimeric antigen receptor (CAR) constructs which bind and activate cells expressing NHG2D ([0359]; [0365]).
It would have been prima facie obvious for one of ordinary skill before the effective filing date of the claimed invention to further combine the teachings of Bigelow by modifying the NK engager or nucleotide sequence thereof by fusing the NKG2D encoding NK engager to a CD3 zeta signaling domain to produce a CAR in order to arrive at the instantly claimed invention because the combination of prior art teachings results in a predictable result of producing an NKG2D-CAR-containing multi-specific antibody that can be generated for the benefit of binding and activating NKG2D-expressing cells.
Claims 43 and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Bigelow as applied to claims 40, 42, 50, and 52 above; and, further in view of Muthumani, et al. WO2020160310A1 (publication date: 08/06/2020; effective filing date: 01/30/2019; herein referred to as Muthumani).
Bigelow teaches A nucleic acid that encodes for an NK engager that binds to a sialic acid-binding receptor binding antibody linked to a target cell binding antibody that binds tumor antigen, and compositions thereof, as applied to claims 40, 42, 50, and 52 above.
Bigelow does not teach that the tumor antigen is selected from FSHR, HER2, IL13Rα, EGFRvIII, and BARF1 (instant claims 43 and 53).
Muthumani teaches bispecific T cell engagers targeting cancer antigens and methods of use in cancer therapeutics (title; abstract). Muthumani teaches that the bispecific engager can comprise an antibody or fragment thereof that specifically binds to an NK cell and an antibody or fragment thereof that specifically binds to a tumor antigen, wherein tumor antigens include EGFR, FSHR, and HER2 (p.42
It would have been prima facie obvious for one of ordinary skill before the effective filing date of the claimed invention to combine the teachings of Bigelow with the teachings of Muthumani by modifying the nucleic acid encoding a multi-specific binding construct (as taught separately by Bigelow and Muthumani) to include or instead use an antibody that specifically binds to Siglec-9 (as taught by Bigelow) and/or a an antibody or fragment that binds tumor cell antigen targets EGFR, FSHR, or HER2, to arrive at the instantly claimed invention because the combination of prior art teachings results in a predictable result of producing an NK cell and tumor cell multi-specific antibody for the benefit of affording improved immune cell response for the treatment of cancer.
Allowable Subject Matter
Claims 44 and 54 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jami M Gurley whose telephone number is (571)272-0117. The examiner can normally be reached Monday - Friday, 8am - 4pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
Prosecution Insights