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 .
Notice of Change of Examiner
The Examiner of your application in the USPTO has changed. To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Examiner Samantha Lake Hopkins in Art Unit 1641.
Election/Restriction
Applicant’s election without traverse of Invention I and/or species of survivin as the tumor antigen protein and TNFR Superfamily agonist glycoprotein fragment, in the reply filed on 12JAN2026 is acknowledged.
Upon further consideration, the requirement for an election of species of an immuno-oncology agent belonging to the TNFR Superfamily agonist or checkpoint inhibitor as set forth in the restriction requirement mailed 20NOV2025 is hereby withdrawn. For clarity, the examiner will evaluate the immuno-oncology agent as a TNFR Superfamily agonist or checkpoint inhibitor as drawn to in claims 31, and 33-37.
Claims 6-9 and 42-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or tumor antigen protein species. Election was made without traverse in the reply filed on 12JAN2026.
Claim Status
Claim 10 was inadvertently omitted in the originally filed claims and claims 11-27 have been canceled.
Claims 28-44 are new.
Claims 1-9 and 28-44 are pending in the instant application (i.e., Claim(s) 1 and 42-44 is/are independent).
Claims 6-9 and 42-44 are withdrawn.
Claims 1-5 and 28-41 are examined on the merits.
Priority
The present application is a 371 National Stage of PCT International Application No. PCT/GB/2020/052794, filed 27OCT2021, which claims foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of UK Application No. 2017119.5 filed on 28OT2020 has been received and is acknowledged.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 08AUG2023 and 12JAN2026 is/are acknowledged and the references cited therein have been considered.
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 p 45 (i.e., PF1-8 of mROP-Survivin and ROP-HPV16 E7 do not appear as individual sequences in the sequence listing).
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.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d) (see for example p 44-45, including the PF sequences and LRMK sequence (i.e., SEQ ID NO: 17) and in claim 29).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, 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.
Specification
The disclosure is objected to because of the following informalities:
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see for example p 37 and 66). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Examiner notes that any references at the end of the specification that are not included in the IDS or PTO-892 have not been considered.
Appropriate correction is required.
Claim Objections
Claims 29, 32, 37, and 40 are objected to because of the following informalities:
Claim 29 contains the amino acid sequence “LRMK” rather than SEQ ID NO: 17. In accordance with 37 CFR 1.821(d), the claims are required to include a sequence identification number.
Claims 32 and 37 contain a typographical error: The “.” between “mg” and “kg” should be corrected to “·” (i.e., middle dot to denote multiplication).
Claim 32 should be modified to include the phrase, dose, for example, “…comprises a dose between 1 μg·kg-1….”
Claim 40 is missing a “.” at the end of the claim.
Appropriate correction is required.
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 and 28-41 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 and providing written description support for:
“A method for the treatment of cancer in a subject comprising administering a therapeutically effective amount of:
a polypeptide comprising:
overlapping peptide fragments derived from tumor antigens and
an exogenous cathepsin S cleavage site sequence located between each of the overlapping peptide fragments; and
an immuno-oncology agent;
wherein the polypeptide amino acid sequences comprise SEQ ID NOs: 18, 51, or 49;
wherein the immuno-oncology agent is selected from the group consisting of an anti-41BB antibody or an anti-PD1 antibody; and
wherein the polypeptide is administered with monophosphoryl lipid A adjuvant every seven days and the immuno-oncology agent is administered every three days to the subject for up to 40 days.” (i.e., claim 1 with the added limitations of claims 3, 5, withdrawn claim 9, 28-30, 36, and 38-41); does not reasonably provide enablement or support for more. Furthermore, claims 2-5 and 28-41 are also rejected since they depend on claim1, but do not remedy this deficiency.
In this instance, applicant has broadly claimed a method of treatment for cancer in a subject comprising administering to the subject: (a) a polypeptide comprising: (i) two or more peptide fragments derived from essentially any tumor antigen protein and (ii) one or more exogenous cathepsin cleavage site sequences located between the two or more peptide fragments and (b) essentially any immuno-oncology agent, which is not fully enabled because:
The breadth of selecting a tumor antigen and fragments thereof;
The prior art teaches at least 2000 tumor antigens and after selection of the tumor antigen, the prior art and the instant specification teaches that the specific fragments may be selected for spanning the tumor antigen or as a result of screening for optimal immunogenicity;
The breadth of selecting an immuno-oncology agent;
The prior art teaches nearly 50 FDA and/or EMA approved immuno-oncology agents as of April 2020 which comprise a variety of different structures and targets;
The teaching of the specification that the polypeptide comprising the overlapping peptide fragments are administered with an adjuvant; and
The undue experimentation required for one of ordinary skill in the art to use this invention.
Additionally, the broadest claim lacks written description support because one of ordinary skill in the art would reasonably conclude that the applicant was not in possession of the full breadth of the claimed genus: a polypeptide comprising essentially any two or more tumor antigen peptide fragments and essentially any immuno-oncology agent. It is noted that applicant has not claimed a product, but rather a method of administering two products. However, artisans must reasonably be in possession of the genus product(s) in order to be in possession of methods of administering said product(s). As has been discussed above, the broadest claims describe the administered product based upon a breadth of tumor antigen fragments and potential immuno-oncology agents. As such describing the administered reagent based upon any number of tumor antigen fragments or as any immuno-oncology agent fails to necessarily provide a structure that gives rise to the aforementioned properties.
As was well-known in the art at the time of filing, more than 2000 tumor antigens have been identified with most of them being self-antigens (Yang, et al., Cell Mol Immuno, 2005, 2 331-341, see abstract). It was also well known in the art at the time of filing that in the field of cancer vaccines, using a tumor antigen proteins or peptides (i.e., immunogens) that triggered T cell activation against said tumor antigens was beneficial to cancer patients (Rabu, et al., Oncoimmunology, 2019, 8, 1-10, see introduction). Specifically, utilization of synthetic long peptides (SLPs), which are peptide fragments of tumor antigens, typically defined as 25-35 amino acid residues in length that can be administered as a mix of up to a dozen units to cover a wide range of T cell activation have been found to be more effective than the full-length tumor antigen protein or a combination of short peptide fragments (Rabu, introduction). In many instances, the choice of SLP relied primarily on a defined CD8 epitope, however careful selection of SLPs for well-defined CD8 and CD4 epitopes results in a more optimal immunogen, for example, separation of naturally overlapping epitopes, linking epitopes that are otherwise far apart on the natural antigen, or improved immunogen response (Rabu, introduction). This is further supported by Vergati, et al., which teach that the use of specific proteins or peptides as targets for immunotherapy clearly requires a careful choice of the targeted TAAs and their epitopes, involving knowledge of their structural and functional characteristics (Vergati, et al., J Biomed Biotechnol, 2010, 1-13, section 3). Vergati, et al., also teach that in the instance where the peptides have relatively poor immunogenicity, may necessitate administration with an adjuvant (Vergati, section 3). Furthermore, the classification of immuno-oncology agents is challenging and there is significant crossover and ambiguity with emerging agents (Carter, et al., Pharm J, 2020, 304, S2-S27, see Classification of immuno-oncology agents section). Per Carter, et al., there are nearly 50 FDA and/or EMA approved immuno-oncology agents as of April 2020 (Tables 1-4), which encompass ICPI or naked mAbs directed to immune check points, naked mAbs directed toward other external and internal cellular targets, ADCs and immunotoxins, and an active mechanism of action (i.e., CART cell therapy, cancer vaccines, etc.). Accordingly, the skilled artisan would be unable to make and use the broadest claimed invention without undue experimentation or envisage the structure of the polypeptide comprising two or more tumor antigen peptide fragments and an immuno-oncology agent directed at any number of targets and having a variety of structures given the state of the art.
The specification teaches recombinant overlapping protein (ROP) fragments of specific tumor antigens, survivin and HPV16E7, comprising eight or more, or four overlapping protein fragments, respectively, each linked via LRMK sequence, which is a cathepsin S cleavage sequence, and are administered in combination with either anti-41BB (i.e., BE0239) or anti-PD1 antibodies, wherein the ROPs are administered with monophosphoryl lipid A adjuvant (i.e., MPL) subcutaneously every 7 days and the antibodies were administered intraperitoneally every 3 days for up to 40 days (Example 2 and 4). The specification further discloses that recombinant overlapping peptides were designed to cover the whole sequence of the protein(s) of interest (i.e., tumor antigens) and in other embodiments only the most immunogenically relevant sections of the protein(s) of interest (i.e., tumor antigens) were represented in the peptide fragments, which were then linked via the LRMK, cathepsin S cleavage sequence site (Example 1). Although the claims are drawn to a breadth of tumor antigen peptide fragments and immuno-oncology agents, the experimental data teach ROP-survivin (i.e., comprising nine survivin fragments, SEQ ID NO: 18), mROP-survivin (i.e., comprising eight survivin fragments, SEQ ID NO: 51), and ROP-HPV16E7 (comprising four HPV16E7 fragments, SEQ ID NO: 49), wherein in a singular example the ROP-survivin was used in combination with anti-41BB (i.e., BE0239) (see working example 2).
Therefore given the state of the prior art and descriptive support from the specification,
“A method for the treatment of cancer in a subject comprising administering a therapeutically effective amount of:
a) a polypeptide comprising:
overlapping peptide fragments derived from tumor antigens and
an exogenous cathepsin S cleavage site sequence located between each of the overlapping peptide fragments; and
b) an immuno-oncology agent;
wherein the polypeptide amino acid sequences comprise SEQ ID NOs: 18, 51, or 49;
wherein the immuno-oncology agent is selected from the group consisting of an anti-41BB antibody or an anti-PD1 antibody; and
wherein the polypeptide is administered with monophosphoryl lipid A adjuvant every seven days and the immuno-oncology agent is administered every three days to the subject for up to 40 days.” is enabled and the function of treating cancer in a subject is supported by the specific structures of the polypeptide and immuno-oncology agent.
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 1-5, 28-31, 33-36, and 38-41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of co-pending Application No. 18/506420, herein referred to as “reference application” in view of Bartkowiak, et al., (PNAS, 2015, 112, E5290-E5299), herein referred to as “Bartkowiak.”
The co-pending claims of the reference application recite: A method for the immunization and/or treatment of a subject comprising administering to the subject the formulation comprising i) a polypeptide comprising two or more peptide fragments and one or more protease cleavage site sequences located between each of the two or more peptide fragments, wherein a first peptide fragment comprises a first sequence derived from a native protein sequence and wherein a second peptide fragment comprises a second sequence derived from the native protein sequence; and ii) the native protein sequence or a portion thereof (i.e., claim 20, dependent on claim 1). The formulation of claim 1, comprising one or more overlapping sequences between 2 and 31 amino acids in length (i.e., claim 2). The formulation of claim 1, wherein the one or more cleavage site sequences is an exogenous protease cleavage site (i.e., claim 3). The formulation of claim [3], wherein the protease cleavage site sequence is a cathepsin S and LRMK cleavage sequence (i.e., claim 4). The formulation of claim 1, further comprising a pharmaceutically acceptable carrier (i.e., exemplary delivery vehicle according to the instant application, see p 4 of the originally filed specification) (i.e., claim 5). The formulation of claim 1, wherein the native protein sequence is survivin, chosen from an one of the following survivin isoforms: isoform 1, 2, 3, 4, 5, 6, and 7 (i.e., claim 13). The formulation of claim 13, wherein at least one of the two or more peptide fragments comprises a sequence with at least 90% identity to a sequence selected from: MGAPTL…., and wherein the polypeptide elicits an immune response or is immunostimulatory or wherein the two or more peptide fragments comprise a sequence with at least 90% identity to: PTENE…., and wherein the polypeptide elicits an immune response (i.e., claims 14-15). A method for the immunization and/or treatment of a subject comprising: a) administering the native protein sequence or portion thereof according to claim 1, or one or more polynucleotides encoding the native protein sequence or portion thereof, and b) administering the polypeptide according to claim 1, or one or more polynucleotides encoding the polypeptides (i.e., claim 22). The method according to claim 22, wherein the native protein sequence or portion thereof, or one or more polynucleotides encoding the native protein sequence or portion thereof are administered simultaneously, sequentially, or separately to the polypeptide or one or more polynucleotides encoding the polypeptide (i.e., claim 23).
In this instance, because the method for the immunization and/or treatment of a subject comprising administering to the subject the formulation comprising i) a polypeptide comprising two or more peptide fragments and one or more protease cleavage site sequences located between each of the two or more peptide fragments, wherein a first peptide fragment comprises a first sequence derived from a native protein sequence and wherein a second peptide fragment comprises a second sequence derived from the native protein sequence; and ii) the native protein sequence or a portion thereof of the reference application is silent on the polypeptide and the native protein sequence, the specification was consulted to determine the scope of the generic term of native protein sequence. Per the specification of the reference application, the native protein sequence comprises survivin and the recombinant overlapping peptide, ROP-mSurvivin (i.e., SEQ ID NO: 47 which has a 99% query match to SEQ ID NO: 51 of the instant application, see OA.APPENDIX), comprises multiple fragments of mSurvivin (i.e., tumor antigen and self-antigen) that are linked by an LRMK cleavage sequence, was administered with adjuvant or adjuvant and mSurvivin protein (p3 and Example 2).
However, they do not claim: administration of a polypeptide and an immuno-oncology agent, wherein the immuno-oncology agent is a glycoprotein 4-1BB agonist, or wherein the polypeptide and immuno-oncology agent are administered repeated periodically, or simultaneously, separately, or sequentially.
Nevertheless, Bartkowiak teaches a peptide-based vaccine which was co-administered with a 4-1BB agonist antibody providing for a synergistic therapeutic effect, which was not observed in combination with CTLA-4 or PD-1 inhibitors (see entire document, specifically see abstract, introduction, and Fig 2A). Specifically, treatment using the peptide-based vaccine alone resulted in the 75% survival being 25 days, while treatment using the peptide-based vaccine and anti-41BB antibody resulted in the 75% survival being extended to 35-50 days (see Fig 2A). Intranasal treatment with the peptide-based vaccine occurred twice at 5 day intervals and intraperitoneal treatment with the antibody occurred on days 5, 8, and 11 post-tumor challenge (i.e., separately and simultaneously or sequentially) (see Vaccination and Immunotherapy section).
It would have been obvious to artisans to modify the issued methods of the reference application to include administration of the immuno-oncology agent of 4-1BB, as taught by Bartkowiak. This is because Bartkowiak teaches that the combination of a peptide-based cancer vaccine in combination with an anti-41BB antibody (i.e., agonist) results in synergistic therapeutic effects as observed in the extension of percent survival for the peptide-based vaccine alone vs the peptide-based vaccine and the anti-41BB antibody. One would have been motivated to do so, given the direction by the reference application that the method could be modified because the formulation of claim 1 contains the open language, “comprising” indicating that the formulation could further comprise additional components, for example a pharmaceutically acceptable carrier, an adjuvant, or in this instance an immuno-oncology agent. There would have been a reasonable expectation of success, given the knowledge that by adding an anti-41BB agonist to a peptide-based vaccine, as taught by Bartkowiak would lead to a synergistic effect in treating cancer in a subject.
This is a provisional nonstatutory double patenting rejection.
Claim Rejections - 35 USC § 102
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.
Claims 1-4, 28, 30-36, and 38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2017/120222 A1 (Cour Pharmaceuticals Development Company, Inc., et al., 13JUL2017, WIPO of US 2019/0365656A1 which is included in IDS), herein referred to as “’222.”
‘222 teaches two or more immunogenic epitopes (i.e., tumor antigens) linked by protease specific linkers, such as cathepsin S cleavable linkers, which are encapsulated (i.e., delivery vehicle) and are administered at 0.01 mg/kg (i.e., 10 μg/kg) twice monthly (7 days apart) for 6 months (i.e., repeated periodically) in combination with an anti-PD1 antibody (i.e., immuno-oncology agent or immune checkpoint inhibitor) for cancer treatment (see ¶00163, ¶0016, and ¶00230-00233).
Therefore, the prior art anticipates the invention as presently claimed.
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, 28-31, 33-36, and 38-41 are rejected under 35 U.S.C. 103 as being unpatentable over Cai, et al., (Oncotarget, 2017, 8, 76516-76524, included in IDS), herein referred to as “Cai” and in view of Bartkowiak, et al., (PNAS, 2015, 112, E5290-E5299), herein referred to as “Bartkowiak.”
Cai teaches treatment of cancer using recombinant overlapping peptides of survivin or HPVE7 (i.e., tumor associated antigens and self-antigen or non-self-antigen, respectively) comprising a cathepsin S cleavage site (i.e., LMRK) to link the overlapping peptides (i.e., exogenous cathepsin cleavage site sequence between the peptide fragments) (see entire document, specifically see Recombinant protein antigens containing overlapping sequences section). Additionally, Cai teaches that immunization with TSAs is an effective way of stimulating immune responses against tumors, but the magnitude and duration of the response is not usually sufficient on its own to result in tumor clearance, which indicates that the ROP have significant potential to be used in a combination approach to immunotherapy, such as, checkpoint inhibition and/or immune stimulation (see Discussion section). Cai further teaches that the ROP is administered with monophosphoryl lipid A (i.e., an adjuvant or pharmaceutically acceptable excipient or delivery vehicle).
However, they do not teach: administration of a polypeptide and an immuno-oncology agent, wherein the immuno-oncology agent is a glycoprotein 4-1BB agonist, or wherein the polypeptide and immuno-oncology agent are administered repeated periodically, or simultaneously, separately, or sequentially.
Nevertheless, Bartkowiak teaches a peptide-based vaccine which was co-administered with a 4-1BB agonist antibody providing for a synergistic therapeutic effect, which was not observed in combination with CTLA-4 or PD-1 inhibitors (see entire document, specifically see abstract, introduction, and Fig 2A). Specifically, treatment using the peptide-based vaccine alone resulted in the 75% survival being 25 days, while treatment using the peptide-based vaccine and anti-41BB antibody resulted in the 75% survival being extended to 35-50 days (see Fig 2A). Intranasal treatment with the peptide-based vaccine occurred twice at 5 day intervals and intraperitoneal treatment with the antibody occurred on days 5, 8, and 11 post-tumor challenge (i.e., separately and simultaneously or sequentially) (see Vaccination and Immunotherapy section).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the peptide-based vaccine disclosed by Cai by administering an anti-41BB antibody agonist disclosed by Bartkowiak. One would have been motivated to do so, given the teachings of Cai that the recombinant overlapping peptides could be beneficial when used in combination with immunotherapy (i.e., immuno-oncology treatments). There would have been a reasonable expectation of success, given the knowledge that a combination HPV peptide-based vaccine in combination with an anti-41BB antibody agonist lead to synergistic therapeutic effects and therefore the effective treatment of cancer upon administration, as taught by Bartkowiak.
Thus, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time of filing.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA L. HOPKINS whose telephone number is (703)756-4666. The examiner can normally be reached Mon-Thurs 6:00 AM to 4:00 PM EST.
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/SAMANTHA LAKE HOPKINS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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