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 is a continuation application that claims priority to International Application No. PCT/US2022/040485 filed 08/16/2022, which claims the benefit of the prior-filed United States Provisional Patent Application No. 63/233,966 filed 08/17/2021.
Status of Application/Claims
The preliminary amendment, filed 10/14/2024, is acknowledged. Claims 8-14, 18, 20-29, and 34-53 are canceled. Claims 3-7, 15-17, 19, and 30-33 are currently amended. Claims 1-7, 15-17, 19, and 30-33 are currently pending and are examined on the merits herein.
Information Disclosure Statements
Four information disclosure statements (IDSs) were filed on 07/12/2024. One of the IDSs appears to have been uploaded in duplicate; thus, all references in the duplicate have been marked as not considered by the examiner.
PDFs for the following foreign references were filed but were not listed on any IDS: WO2014/094799A1, CN103865060A, WO2009/003965A1, JP2007177014A, WO2021/055752A1, WO2019/246392A1, WO2016/126719A1, WO2017/024237A1, WO2018/036701A1, CN107759697A, and WO2004/009136A2. Thus, these references were not considered by the examiner.
The following foreign references were listed on the IDSs but no pdfs were provided: CN10775997a, WO198700195, WO199316185, WO199429351, WO1996027011, WO199730087, WO199858964, WO199951642, WO2001079271, WO2002076489, WO200243478, WO200359934, WO2004041865, WO2005025586, WO2005035778, WO2005053742, WO2011124718, WO2012059486, WO2016200645A1, WO2019173832A2, WO2019222294A1, WO2018071918, WO2019214757A1, WO2019222295A1, WO2021016599A1, WO2010020766A2, WO2011123683A2, WO2014100014A1, WO2021062406A1, WO2002055098A2, WO2020232305A1, WO2016126719A1, CN103298935A, CA3031955A1, CN1599867A, CN107207603A, CN1070082812A, WO2018097308A1, WO, 2017156178A1, WO2018085555A1, WO2018236701A1, WO2019036031A2, WO2018204528A1, WO2009025846A2, WO20060166329A1, WO20200252264A1, WO2021202673A1, WO2009103965A1, WO20030139575A1, WO2019018828A1, WO2021202678A1, WO2021202675A1, WO2021097376, WO2023023070, WO2023023065, WO2023023131, and WO2021236676.Thus, these references were not considered by the examiner.
Additionally, the foreign reference WO2020069398A1 was listed in duplicate on 2 different IDSs. This reference was marked out/lined through on the IDS wherein WO2020069398A1 is listed as foreign reference #2.
Further, the Zapata, et al. literature article is incorrectly filed as a foreign reference.
PDFs for the following non-patent literature references were uploaded but were not listed on any IDS: Duret, et al. 2014; Rochman, et al. 2009; Yu, et al. 2001; El-Sherbiny, et al., 2015; Trinchieri, et al., 2003; Rice, et al., 2006; Rosano, 2014; Sadlack, et al., 1993; Waterman, 1981; Chen, et al., 2013; Uhland, 2006; Vartak, et al., 2007; Zhao, et al, 2019; Strohl, et al., 2015; Willerford, et al., 1995; Tolman, et al., 2009; Sheriff, 1990; Suzuki, et al., 1995; Wong, et al., 2016; Zavrsnik, et al, 2017; Berkrot, 2015; Maklakova, et al., 2015; Brooks, et al., 2015; Kumar, et al, 2015; Ulisse, et al., 2009; Jung, 2018; Novoa, et al., 2015; Sivapalan, et al., 2021; Kudo, et al., 2019; Conay, et al., 2004; Kabilan, et al., 2005; Schaefer, et al., 2010; Vasiljeva, et al., 2019; Tregoning, et al., 2021; Patani, et al., 1996; Lawlor, et al., 2014; Yang, et al., 2010; Duret, et al., 2012; Zatsepin, et al., 2004; Kataoka, et al., 1998; and, Sermet-Gaudelus, et al., 2001. These references must be cited on an IDS if they are to be considered.
The following non-patent literature references were listed on the IDSs but no pdfs were provided: Berger, 2009; Bessard, 2009; Conlon, 2015; Beclerck, 2004; Denise Scrombolas, 2014; Desnoyers, 2013; Giesen, 2019; Jabaiah, 2012; Jana, 2013; Kim, 2013; Lasek, 2014; Lebeau, 2013; Lebeau, 2015; Lin, 2018; Bachmann, 1987; Bernett, 2018; Boerner, 1991; Bothmann, 2000; Brodeur, 1987; Carter, 1992; Kratz, 2006; Davies, 1990; Damodaran, 2010; Jefferis, 2009; Klein, 2012; Kozbor, 1984; Mather, 1982; Merchant, 1998; Keunok Jung, 2018; Nygren, 1988; Ramm, 2000; Reyes, 1982; Ripka, 1986; Sali, 2015; Shields, 2001; Shinkawa, 2003; Simmons, 2002; Sola, 2007; Sties, 1994; Tomizuka, 2000; Torgov, 2005; Traunecker, 1991; Urlaub, 1980; and, Verhoeven, 1988. Thus, these references were not considered.
Further, the Benito Salmi et al. reference WO200130460 listed as #15; and, the pdf labeled WO2018/036701A1 do not appear to be related in any way to the application. Applicant is reminded that MPEP §2004 discourages the submission of lengthy lists of documents that are not material to patentability: “It is desirable to avoid the submission of long lists of documents if it can be avoided. Eliminate clearly irrelevant and marginally pertinent cumulative information.”
The information disclosure statements (IDSs) submitted on 07/12/2024 have otherwise been fully considered by the examiner.
Drawings
The drawings are objected to because color drawings were filed. Applicant must either submit an appropriate petition under 35 CF$ 1.84(a)(2) or black and white/grayscale figures:
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Figures 1, 3, and 10 have color drawings.
Specification
The use of the terms Keytruda and Merck & Co, Inc.; 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 Objections
Claim 4 is objected to because of the following informalities: There is no period (.) at the end of the claim in line 3. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4 and 6 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 4 recites “…the anti-PD-1 antibody that comprises a heavy chain and a light chain, and wherein the heavy and light chains comprise the amino acid sequences in SEQ ID NO: 10 and SEQ ID NO: 5, respectively.” However, SEQ ID NO: 5 encodes for an IL-2 binding variable light chain/constant light chain region as recited for “Compounds 1-4.” Thus, it is unclear how the variable light domain is able to form an antigen-binding domain with the heavy chain of SEQ ID NO: 10 which is for an anti-PD-1 binding heavy chain. For further examination, “SEQ ID NO: 5” as it refers to the “anti-PD-1 antibody” is interpreted to mean “SEQ ID NO: 15.”
Claim 6 recites “(or a biosimilar)” in line 2. It is unclear whether the term in parentheses is to be considered as merely an example or a required scope limitation. For purposes of further examination, the term in parentheses is considered not to be required).
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 1-7, 15-17, 19, and 30-33 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. THIS IS A WRITTEN DESCRIPTION REJECTION.
Regarding claims 1-7, 15-17, 19, and 30-33: Claims 1 and 2 are inclusive of a method for treating cancer comprising administering a genus of combination therapies wherein the recited Compounds 1, 2, 3, 4, or amino acid sequence variants thereof corresponding to the first and second polypeptides; thus, the claims allow for any amino acid sequence variant for each of SEQ ID NOs: 1-4 of the first polypeptide and/or SEQ ID NO: 5 of the second polypeptide. Thus, claim 1 encompasses every possible variant for each polypeptide. Claim 2 only requires 80% identity for the amino acid sequences of Compounds 1-4.
The invention is drawn to an activatable prodrug comprising a first and second polypeptide. The specification provides that: “The first polypeptide chain comprises from amino to carboxy terminus: the IL-2 polypeptide—a protease cleavable linker—an anti-human serum albumin (HSA) binding single antibody variable domain—a linker that is preferably protease cleavable—VH and CH1 of an antibody that binds IL-2. The second polypeptide chain comprises a VL and CL of an antibody that binds IL-2 and that together with the VH and CH1 of the first polypeptide chain from a Fab that binds the IL-2 polypeptide” (p.11, [48]). While claims 1 and 2 respectively allow for any variant and a variant requiring only 80% identity to each polypeptide, the specification only provides support for 4 compounds wherein the first polypeptide is encoded by instant SEQ ID NO: 1, 2, 3, or 4, and a second polypeptide encoded by instant SEQ ID NO: 5.
Regarding the IL-2 antigen binding fragments formed by the VH and VL of the first and second polypeptides, respectively: The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (see Paul. Fundamental Immunology, 3rd Edition, 1993, pp. 292-295; herein referred to as Paul). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (p.293, col.1-2, lines 3-8, line 31, and lines 27-30). Regarding the anti-HSA binding single antibody variable domain: The state of the prior art teaches that single domain antibodies comprise three CDRs that are specific for antigen binding (see abstract from Henry and MacKenzie. Antigen recognition by single-domain antibodies: structural latitudes and constraints. MABS (2018), 10:6, p.815-826; herein referred to as Henry).
Regarding the protease cleavable linker: The state of the prior art teaches protease/peptidase specificity and cleavage is dependent the substrate amino acid sequence; and, that some peptidases act on different substrates but that some can act on the same substrates but perform cleavage at a different position (p.5). Further, Rawlings provides a list of peptidases and amino acid positions wherein some positions of the peptide substrate have a invariable amino acids, some positions require a particular type of amino acid (e.g. λ = “aliphatic” Ile, Leu, or Val), and some positions that do not require a preferred amino acid (see Table 4 and legend from Rawlings. Peptidase specificity from the substrate cleavage collection in the MEROPS database and a tool to measure cleavage site conservation. Biochimie (2016), 122, p.5-30; herein referred to as Rawlings). However, it is unclear from the specification and the prior art which amino acid positions from the instantly claimed “cleavable linkers” comprised within the fusion proteins can be mutated while retaining function.
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genus. That is, the specification provides neither a representative number of polypeptides that encompass the genus of antibodies with the claimed function nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the 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 to provide a "representative number” of species.
The “claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.” Ariad Pharmaceuticals, Inc. v. EliLilly and Co.,598 F.3d 1336, 1353 (Fed. Cir. 2010).
Because the disclosure fails to describe common attributes or characteristics that adequately identify members of the genus, and results in a method which is highly variable, the disclosure of the combination therapy comprising administration of Compound 1 for the treatment of melanoma or colon cancer is insufficient to describe the genus of a method for treating cancer. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
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.
Patent 12036266
Claims 1-2 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-12, and 14 of U.S. Patent No. 12036266 (herein referred to as Pat ‘266). Although the claims at issue are not identical, they are not patentably distinct from each other because they both teach a method of treating cancer with an inducible cytokine comprising two polypeptides (instant claims 1-2; Pat ‘266 claim 9), an IL-2 cytokine/cytokine variant polypeptide (instant claims 1-2; Pat ‘266 claims 1, 6-7, an IL-2 cytokine blocking moiety/antibody (instant claims 1-2; Pat 266 claims 1, 10, and 14); a first cleavable linker and second linker (instant claims 1-2; Pat ‘266 claim 1); and, a half-life extension domain (instant claims 1-2; Pat ‘266 claims 1 and 11).
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
Prosecution Insights