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 .
Status of the claims
Claims 1, 4-7, 10-15, 21, 22, 24, 29, 34-38 and 41-43 are pending and are currently examined.
Information Disclosure Statement
The information disclosure statements (IDS)s submitted on 04/06/2023, 06/18/2024 and 08/07/2024 were considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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, 4-7, 10-15, 21, 22, 24, 29, 34-38 and 41-43 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 treating basal cell carcinomas, head and neck squamous cell carcinoma, non-small cell lung cancer, renal cell carcinoma and melanoma, does not reasonably provide enablement for all 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 a method of treating a cancer in a subject in need thereof, comprising administering to the subject (a) about 8 μg/kg, 16 μg/kg, 24 μg/kg, or 32 μg/kg of an IL-2 conjugate, and (b) pembrolizumab, wherein the IL-2 conjugate comprises the amino acid sequence of SEQ ID NO: 1 wherein the amino acid at position P64 is replaced by the structure of Formula (IA):
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Wherein:
Z is CH2 and Y is:
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Y is CH2 and Z is:
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Z is CH2 and Y is:
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Y is CH2 and Z is:
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W is a PEG group having a molecular weight of about 25 kDa - 35 kDa; q is 1, 2, or 3;
X is an L-amino acid having the structure:
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X-1 indicates the point of attachment to the preceding amino acid residue; and
X+1 indicates the point of attachment to the following amino acid residue.
As such, the claim is drawn to a genus of methods of treating any (all?) cancers with the composition claimed.
The specification discloses methods of treating patients having basal cell carcinomas, head and neck squamous cell carcinoma, non-small cell lung cancer and melanoma. In a dependent claim (claim 24) Applicant somehow limits the list of cancer to be treated to: basal cell carcinoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), head and neck squamous cell cancer (HNSCC), classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), urothelial carcinoma, microsatellite unstable cancer, microsatellite stable cancer, gastric cancer, colon cancer, colorectal cancer (CRC), cervical cancer, hepatocellular carcinoma (HCC), Merkel cell carcinoma (MCC), melanoma, small cell lung cancer (SCLC), esophageal, esophageal squamous cell carcinoma (ESCC), glioblastoma, mesothelioma, breast cancer, triple-negative breast cancer, prostate cancer, castrate-resistant prostate cancer, metastatic castrate-resistant prostate cancer, or metastatic castrate-resistant prostate cancer having DNA damage response (DDR) defects, bladder cancer, ovarian cancer, tumors of moderate to low mutational burden, cutaneous squamous cell carcinoma (CSCC), squamous cell skin cancer (SCSC), tumors of low to non-expressing PD-L1, tumors disseminated systemically to the liver and CNS beyond their primary anatomic originating site, and diffuse large B-cell lymphoma (DLBCL ). However, no experimental data are offered for treatment of such an expended arrays of cancers, beyond the aforementioned basal cell carcinomas, head and neck squamous cell carcinoma, non-small cell lung cancer and melanoma treatments. Moreover, cancer is the name given to a collection of related diseases characterized by cellular out of control division and spreading in the surrounding or distant tissues. Cancer can start almost anywhere in the human body, which is made up of trillions of cells. Normally, human cells grow and divide to form new cells as the body needs them. When cells grow old or become damaged, they die, and new cells take their place. When cancer develops, however, this orderly process breaks down. As cells become more and more abnormal, old or damaged cells survive when they should die, and new cells form when they are not needed. These extra cells can divide without stopping and may form growths called tumors. Many cancers form solid tumors, which are masses of tissue. Cancers of the blood, such as leukemias, generally do not form solid tumors. There are more than 100 types of cancer. Types of cancer are usually named for the organs or tissues where the cancers form. Cancers also may be described by the type of cell that formed them, such as an epithelial cell or a squamous cell (see evidentiary references: https://en.wikipedia.org/wiki/List_of_cancer_types- accessed 05/22/2020; and https://www.cancer.gov/about-cancer/understanding/what-is-cancer).
The art is not aware of methods of treatment of cancers with the composition claimed. While IL-2 and IL-2 conjugates may be used in compositions for treating specific cancers, the art at the time that the invention was filed, does not present evidence for treating all cancers. Indeed, even in reviews published recently (Radi et al., An updated review of Interleukin-2 therapy in cancer and autoimmune diseases. J Interfer. & Cytokine Res., 44, 143-157, 2024) shows that combinations using IL-2 and checkpoint inhibitors- e.g. PD-1 antibody- were tested in clinical trials for melanoma and renal cell carcinoma (see table 1). The art reviewed has not indicated the specific IL-2 conjugates claimed instantly and the PD-1 antibody combination. Nevertheless, aby new treatment method needs to be thoroughly tested before usage. Indeed, Im et al. (Harnessing IL-2 for immunotherapy against cancer and chronic infection: a historical perspective and emerging trends. Experimental & Molecular Medicine 56, 1900–1908, 2024) indicate that, various efforts have been made to engineer IL-2 to avoid severe side effects and off-target effects caused by IL-2wt. Most of these initiatives have focused on reducing binding to IL-2Rα. However, as seen in previous clinical studies involving engineered IL-2, encouraging results from preclinical studies do not always translate to positive outcomes in clinical trials (concluding remarks). Thus, given the uncertainty in the art as to use IL-2 conjugates, with or without PD-1 antibodies, the fact that the conjugates appear to be novel and the breadth of the claims of treating such a vat arrays of cancers, it is submitted that an enormous amount of experimentation would need to be performed, with unpredictable results. Such an amount of experimentation is considered to be undue and thus the claims are enabled only for treating basal cell carcinomas, head and neck squamous cell carcinoma, non-small cell lung cancer, renal cell carcinoma and melanoma, but not for the full scope of the claims.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4-7, 10-15, 21, 22, 24, 29, 34-38 and 41-43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-28 of copending Application No. 16/993,967(reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the IL-2 of SEQ ID NO: 3 of the reference is identical to IL-2 of SEQ ID NO:1 of the instant Application and, as such, the conjugates have the same structures and the cancers to be treated in combination with anti PD-1 antibody are also claimed in the reference Application.
If the reference Application is allowed, first, it would anticipate claims 1, 4-7, 10-15, 21, 22, 24, 29, 34-38 and 41-43 of the instant Application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 4-7, 10-15, 21, 22, 24, 29, 34-38 and 41-43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-48 of copending Application No. 18/447,808 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference Application claims a method of treatment of lung cancer with the same reagents and administration regimen as claimed by instant Application’s claims. If the reference Application is allowed, first, it would anticipate claims 1, 4-7, 10-15, 21, 22, 24, 29, 34-38 and 41-43 of the instant Application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 4-7, 10-15, 21, 22, 24, 29, 34-38 and 41-43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-4, 14-17, 19, 37, 44, 45, 47, 50, 51, 53, 62,-64, 70-71 of copending Application No. 18/296,711 (reference application). The refence Application claims a method of treatment of cancer with the same IL-2 conjugates and administration regimen as claimed by instant Application’s claims. The reference Application does not claim the use of pembrolizumab for treatment. However the use of pembrolizumab with IL-2 or conjugates of it for treating cancer was routinely used in the art, as evidenced by U.S. Pat. No. 10,358,496 (col. 4, lines 14-21).
Thus, it would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to have combined the teaching of 18/296,711 with the disclosure of U.S. Pat. No. 10,358,496 and treat certain cancers with a reasonable expectation of success. This is because the skilled artisan would have used known techniques and reagents to treat cancer.
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.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLY GERALD STOICA whose telephone number is (571)272-9941. The examiner can normally be reached M-F 8-5 EST.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/ Primary Examiner, Art Unit 1647