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 with traverse of Group II (claims 1-5 (in part), 11-15, 16-19, 20-23 and 26 (in part), in the reply filed on 01/07/2026 is acknowledged. The traversal is on the grounds that: “… given the unified nature of the BCG antigen coated technology to elicit an immune response, and that one skilled in the art would recognize that a technology using peptide antigens to treat cancer could also be used to treat an infection, the claims relate to a single general inventive concept.”
This is not found persuasive because the type of products used for treating an infection are different than the type of products needed to treat cancers.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-23 and 26-29 are pending; claims 6-10 and 27-29 are withdrawn from prosecution for being drawn to non-elected subject matter. Claims 1-5, 11-23 and 26, as drawn to an attenuated Mycobacterium bovis of the strain Bacillus Calmette-Guerin (BCG) for use in humans to treat cancers, wherein said BCG is coated with a plurality of peptide antigens, are examined.
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 1-5, 11-23 and 26 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 compositions used for treating melanoma and colon cancer, does not reasonably provide enablement for preventing any cancer or treating other cancers. 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 claims are drawn to an attenuated Mycobacterium bovis of the strain Bacillus
Calmette-Guerin (BCG) for use in humans to prevent or treat a disease wherein said BCG is coated with a plurality of peptide antigens capable of eliciting an immune reaction against said disease in said human and wherein said plurality of peptide antigens are attached to said bacteria using a poly-lysine or poly-arginine peptide linker.
The specification disclosed the use of an attenuated BCG coated with Trp-2, gp100 or AH1 peptide antigens, attached to the bacteria by a poly-lysine peptide linker, to treat melanoma or colon cancer cells xenografted in mice.
The art is aware of the involvement of the antigens gp100 and Trp-2 in melanoma and of the antigen AH1 in colon cancer (see evidentiary references: Kirkin et al. (Melanoma-associated antigens recognized by cytotoxic T lymphocytes. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica, 106, 665-79, 1998) and Stringhini et al. (Immunotherapy of CT26 murine tumors is characterized by an oligoclonal response of tissue-resident memory T cells against the AH1 rejection antigen. Eur. J. Immunol., 50, 1591-1597, 2020. Epub 2020 June 9). The art is not aware of using the above mentioned peptide antigens for treating other types of cancers.
Cancer is a group of disease diseases that comprises a vast number of types (each type of cell in the organisms may develop characteristics associated with the defining properties of the cancer cells (see evidentiary references: (List of Cancer types, https://en.wikipedia.org/wiki/List_of_Cancer_types) and (What is cancer? https://www.cancer .gov/about-cancer/understanding/what-is-cancer).
As indicated supra, the Specification presents evidence of using constructs that comprise only gp100, Trp-2 and AH1 for treating xenografted mice with melanoma cancer cells and CT26 (colon cancer cells). While other constructs comprising could theoretically be made, each compound would need to be painstakingly tested for treatment of any (all?) cancers with an unpredictable outcome. Such an amount of experimentation, given the great number of tumor associated antigens and the vast number of types of cancer, and the unpredictability of outcomes, is considered undue. Thus, the compositions claimed, may be used for treatment of melanoma and colon cancer but not for the full scope of the independent claim 1 or claim 15.
Regarding the prevention of cancer aspect, the phrase "preventing a disorder", given its broadest reasonable interpretation in light of the teachings in the specification, requires that absolutely no cell, nor tissue, or individual would present any symptom of a cancer after treatment with the composition claimed. There is no evidence, either in the specification or in the prior art, that any method to date can accomplish this goal. There is no support for the prevention of any cancer, as is required by the claims, and neither can such support be obtained through reasonable extrapolation of the data or teachings in the art.
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.
Claims 1-5, 11-13 and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable over Liao et al. (Improving the immunogenicity of the Mycobacterium bovis BCG vaccine by non- genetic bacterial surface decoration using the Avidin-Biotin system. PLos One, 10, e0145833, 2015 -cited by Applicant) in view of Capasso et al. (Oncolytic adenoviruses coated with MHC-I tumor epitopes increase the antitumor immunity and efficacy against melanoma, Oncoimmunology, 5, e1105429, 2015 – cited by Applicant) and in further view of Kozel et al. (U.S. 9,310,365).
The claims are drawn to an attenuated Mycobacterium bovis of the strain Bacillus
Calmette-Guerin (BCG) for use in humans to prevent or treat a disease wherein said BCG is coated with a plurality of peptide antigens capable of eliciting an immune reaction against said disease in said human and wherein the plurality of peptide antigens are attached to said bacteria using a poly-lysine or poly-arginine peptide linker. The peptide antigens may be MHC-I or MHC-II restricted and may be tumor associated antigens (TAAs), tumor-specific antigens (TSAs) or neoantigens. The composition is comprised in a pharmaceutical composition including a carrier that is designed for administration by a variety of routes, including intradermal, intranasal, subcutaneous, percutaneous, intratumoral, intramuscular, intraarterial, intravenous, intrapleural, intravesicular, intracavitary or peritoneal injection, or oral. Also claimed is a method of treating cancer with the composition claimed.
Liao et al. discloses strategies to improve the current BCG vaccine for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. The novel technology, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine (abstract).
The reference does not teach the attachment of the antigens to BCG by poly-lysine linkers.
Capasso et al. teaches a versatile and rapid system to adsorb tumor-specific major histocompatibility complex class I (MHC-I) peptides onto the viral surface of oncolytic adenoviruses (OAds) to drive the immune response toward the tumor epitopes. By studying the model epitope SIINFEKL, it was demonstrated that the peptide-coated Oad (PeptiCRAd) retains its infectivity and the cross presentation of the modified-exogenous epitope on MHC-I. The SIINFEKL-targeting PeptiCRAd achieves a superior antitumor efficacy and increases the percentage of antitumor CD8+ T cells and mature epitope-specific dendritic cells in vivo. PeptiCRAds loaded with clinically relevant tumor epitopes derived from tyrosinase-related protein 2 (TRP-2) and human gp100 could reduce the growth of primary-treated tumors and secondary untreated melanomas, promoting the expansion of antigen-specific T-cell populations. The PeptiCRAd was tested in humanized mice bearing human melanomas. The immunogenicity of OAds plays a key role in their efficacy and it can be exploited to direct the immune response system toward exogenous tumor epitopes. This system overcomes the immunodominance of the virus and elicits a tumor-specific immune response, making PeptiCRAd a promising approach for clinical testing (abstract). The negative charge of the adenovirus capsid can be used to complex positively charged immunogenic peptides, forming PeptiCRAd and the reference indicated the use of poly-lysine to increase the net charge of the peptide. The MHC-I epitopes adsorbed onto peptiCRAd are efficiently cross presented. Intratumoral injections of PeptiCRAd significantly reduced the tumor’s growth compared with treatment with saline buffer, SIINFEKL peptide or the mixture of OAd and SIINFEKL. Multivalent PeptiCRAd shows enhanced antitumor activity toward distant, untreated melanomas. The authors used two poly K-modified versions of the tumor-specific MHC-I-restricted epitopes SVYDFFVWL (TRP-2180-188) and KVPRNQDWL (human gp10025-33, or hgp100; both expressed by B16-F10 cells (Results). While the reference disclosed poly-lysine linkers, it does not consider its use with BCG vaccines.
Kozel et al. disclosed methods of inducing an immune response to melioidosis including the use of the immunogenic melioidosis polypeptides. A melioidosis-associated polypeptide can also be expressed by the attenuated bacterial vector BCG (Bacillus Calmette Guerin) (col. 27, lines 31-40). Consecutive repeats of immunogenic melioidosis peptides can be joined by a peptide linker between two and ten amino acids in length, such as about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9 or about 10 amino acids in length. The linker is a peptide heterologous to the immunogenic melioidosis peptide such as poly-lysine (col. 31, lines 22-37).
The compositions comprising the vector loaded with the peptide of interest are part of a pharmaceutical composition that also comprises a carrier. The nature of the carrier will depend on the particular mode of administration being employed. For instance, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle. For solid compositions (such as powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate. In addition to biologically neutral carriers, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate (col.12, lines 5-20).
It would have been obvious for a person of ordinary skill in the art to have combined the teachings of Capasso et al. with the disclosures of Liao et al and Kozel et al and obtain a composition comprising an attenuated BCG coated with a variety of antigens linked through poly-lysine linkers with a reasonable expectation of success. This is because the skilled artisan would have used known techniques and reagents to obtain an immune response. A person of ordinary skill in the art is always motivated to pursue the known options within her or his technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Conclusion
No claims are allowed.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647