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 .
Claim Status
Claims 1, 4-6, and 9-13 are pending under examination. Claims 12 and 13 are new. Claims 1, 4-6, and 9-11 are currently amended. Claims 2-3 and 7-8 have been cancelled.
Priority
The Application is the 371 of PCT/JP2020/048667, filed on 12/25/20, and claims foreign priority to JP2019-236947 filed 12/26/19. Applicant has claimed the effective filing date of 12/26/19 based on JP2019-236947 but no translation has been made of record.
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant’s arguments, see Pg 6-9, filed 9/8/2025, with respect to the rejection(s) of claim(s) 1-11 under 35 U.S.C. 112(a) and 102(a)(1)/(a)(2) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of amendment.
Further, Applicants request that the double patenting rejections be held in abeyance is noted but they have been modified and maintained herein.
Claim Rejections - 35 USC § 112
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 4 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 4 recites that the peptide consists of the sequence set forth in SEQ ID NO: 31. Per the Sequence Listing, SEQ ID NO: 31 consists of four non-continuous segments. However, in the instant specification, SEQ ID NO: 31 is described as consisting of SEQ ID NO: 5-linker-SEQ ID NO: 9-linker-SEQ ID NO: 6-linker-SEQ ID NO: 4. Thus, the scope of the claim is indefinite as it is unclear 1) how a peptide might consist of four non-contiguous segments and 2) whether or not SEQ ID NO: 31 does include linker segments that connect the four non-continuous segments. For purposes of examination, SEQ ID NO: 31 is being interpreted per the instant specification, wherein it consists of SEQ ID NO: 5, 9, 6, and 4, in that order, connected via linkers.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 1, from which claim 4 depends, recites that the one or more peptides having 4 linked CTL epitopes comprise 4 CTL epitopes that are linked via linkers. Claim 4 recites that the peptide having 4 linked CTL epitopes consists of the sequence set forth in SEQ ID NO: 31. SEQ ID NO: 31 consists of SEQ ID NO: 5, 9, 6, and 4, in that order, as shown below, but without any linkers connecting them:
SEQ ID NO: 31: DYSARWNEI QIRPIFSNR VYDYNCHVDL LLQAEAPRL
SEQ ID NO: 5 SEQ ID NO: 9 SEQ ID NO: 6 SEQ ID NO: 4
Thus, claim 4 does not recite all the limitations of its parent claim, claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim(s) 1, 4-6, and 9-13 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Tanaka (US2021/0236613 A1, filed 6/28/2019).
Tanaka teaches a cancer treatment that exhibits antitumor effect and causes less adverse reactions by administering a peptide having 4 linked CTL epitopes and an immune checkpoint modulator in combination. The antitumor effect in humans can be evaluated by providing a cell coexpressing an epitope peptide of a human tumor antigen derived from SART2 and human HLA-A24 (Abstract, [0011]).
Tanaka teaches that the invention comprises a series of peptides having 4 linked CTL epitopes; specifically disclosed are the peptides SEQ ID NO: 1-28, which correspond to and are identical to the instant SEQ ID NO: 1-28, including SEQ ID NO: 4, 5, 6, and 9 as recited in instant claim 1, and SEQ ID NO: 24 as recited in instant claim 9 (Sequence Listing, Pg 24-35). Per the claim interpretation described above under 112(b), Tanaka also teaches SEQ ID NO: 31, which consists of SEQ ID NO: 5, 9, 6, and 4, in that order, connected via linkers.
Tanaka teaches that any linker can be used to link the 4 CTL epitopes, provided that it is cleaved upon administration to an organism, and the linked CTL epitope peptides can be separated from each other. Examples thereof include an ester bond, an ether bond, an amide bond, a sugar chain linker, a polyethylene glycol linker, and an amino acid linker. Examples of amino acid sequences used as amino acid linkers include arginine dimer (RR), arginine trimer (RRR), arginine tetramer (RRRR), lysine dimer (KK), lysine trimer (KKK), lysine tetramer (KKKK), glycine dimer (GG), glycine trimer (GGG), glycine tetramer (GGGG), glycine pentamer (GGGGG), glycine hexamer (GGGGGG), alanine-alanine-tyrosine (AAY), isoleucine-leucine-alanine (ILA), and arginine-valine-lysine-arginine (RVKR), with arginine dimer (RR) or arginine trimer (RRR) being preferable and arginine dimer (RR) being more preferable. Linkers for use in peptides having linked epitopes are known in the art and can be appropriately selected for use by those skilled in the art ([0165]).
Tanaka teaches that the tumor to be targeted is preferably a SART2-positive malignant tumor ([0220]).
Additionally, Tanaka notes that cancers that can be targeted by the present invention include not only primary tumors but also cancer that has metastasized to other organs. The antitumor agent of the present invention may be the one for use in postoperative adjuvant chemotherapy which is performed for preventing recurrence after surgical extirpation of the tumor, or may be the one for use in preoperative adjuvant chemotherapy which is performed before surgical extirpation of tumor ([0221]). Thus, Tanaka anticipates claims 1, 4-6, 9, 10, and 11.
Further, the peptide having 4 linked CTL epitopes according to the present invention can further have a peptide sequence consisting of hydrophilic amino acids. Such peptide sequence can be added to the N terminus and/or the C terminus of the peptide having 4 linked CTL epitopes, and is preferably added to the N terminus. Such a peptide sequence consists of 1 to 15, preferably 2 to 10, and more preferably 3 to 5 hydrophilic amino acids selected from the group consisting of arginine, histidine, lysine, threonine, tyrosine, serine, asparagine, glutamine, aspartic acid, and glutamic acid. For example, arginine trimer (RRR) or arginine tetramer (RRRR) can be used as such a peptide sequence. Examples of peptides having 4 linked CTL epitopes comprising such peptide sequences added thereto include RRR-TPV06 and RRRR-TPV06 (TPV06 corresponds to SEQ ID NO: 24 of Tanaka and the instant application), RRR- or RRRR-TPV07 (TPV07 corresponds to SEQ ID NO: 25 of Tanaka and the instant application), and RRR- or RRRR-TPV08 (TPV08 corresponds to SEQ ID NO: 26 of Tanaka and the instant application) ([0184]). A peptide comprising such peptide sequence consisting of hydrophilic amino acids is known to have improved solubility in an aqueous solvent. With the addition of such peptide sequence to the peptide having 4 linked CTL epitopes according to the present invention, the solubility of the peptide having 4 linked CTL epitopes in an aqueous solution can be improved ([0185]). Thus, Tanaka anticipates claims 12 and 13.
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.
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.
Claim(s) 1, 4-6, and 9-13 are rejected under 35 U.S.C. 103 as being unpatentable over Fukaya et al. (US10,137,183 B2, filed 10/20/14, published 11/27/18) in view of Brown et al. (Loss of antigen cross-presentation after complete tumor resection is associated with the generation of protective tumor-specific CD8(+) T-cell immunity. Oncoimmunology. 2012 Oct 1;1(7):1084-1094.).
Fukaya teaches a cancer antigen peptide that can be administered to a wide range of cancer patients in the form of a peptide vaccine for cancer without the need for HLA typing and regardless of the HLA types of patients. Such a peptide having 4 linked CTL epitopes is obtained by linking 4 CTL epitope peptides selected from among CTL epitope peptides derived from tumor antigen molecules that are reported to have the capacity for CTL induction via linkers (Abstract).
Fukaya teaches the peptides SEQ ID NO: 1-18, which correspond to and are identical to the instant SEQ ID NO: 1-18, as well as the peptides SEQ ID NO: 22-27, which correspond to and are identical to the instant SEQ ID NO: 19-24 (Sequence Listing, Col. 25-51). SEQ ID NO: 27 of Fukaya, which corresponds to the instant SEQ ID NO: 24, consists of the sequence “Asp Tyr Ser Ala Arg Trp Asn Glu Ile Arg Arg Gln Ile Arg Pro Ile Phe Ser Asn Arg Arg Arg Val Tyr Asp Tyr Asn Cys His Val Asp Leu Arg Arg Leu Leu Gln Ala Glu Ala Pro Arg Leu” and encompasses the instant SEQ ID NO: 5 (Asp Tyr Ser Ala Arg Trp Asn Glu Ile), 9 (Gln Ile Arg Pro Ile Phe Ser Asn Arg), 6 (Val Tyr Asp Tyr Asn Cys His Val Asp Leu), and 4 (Leu Leu Gln Ala Glu Ala Pro Arg Leu) interspersed with arginine dimer linkers (bolded for emphasis). Per the claim interpretation described above under 112(b), Fukaya also teaches SEQ ID NO: 31, which consists of SEQ ID NO: 5, 9, 6, and 4, in that order, connected via linkers, such as the arginine dimers of SEQ ID NO: 24.
Fukaya claims a method for treating cancer comprising administering to a cancer patient the peptide or a pharmaceutical composition containing it (claim 13). These peptides can be included in pharmaceutical compositions as an active ingredient used for cancer immunotherapy (Col. 12, lines 58-62). Fukaya further teaches that the dosage of the pharmaceutical composition according to the present invention can be adequately adjusted in accordance with factors such as the conditions/severity of cancer to be treated, the age of the patient, or the body weight of the patient (amount effective for treatment; Col. 15, lines 17-32).
Fukaya also teaches that SEQ ID NO: 5 is derived from SART2 (Table 2). Such CTL epitope peptides derived from tumor antigen molecules are peptides that result from decomposition of tumor antigens within tumor cells that are then bound to HLA class I molecules and presented on the cell surface, which can be recognized by a tumor-specific CTL and/or induce and/or activate-tumor specific CTLs ([0095]), thus making it obvious to treat SART2-expressing cells with the aforementioned polypeptides.
Fukaya does not explicitly teach administering the above polypeptides after surgery.
Brown describes the impact of tumor resection on the tumor-specific T-cell response (Abstract). Brown states that in situ tumor ablation creates a source of antigens and an immune response that is enhanced by immunotherapy but also notes that there is a decline in dendritic cells (DCs) that cross-present tumor antigens over ~10 days post-surgery. Presumably, the complete removal of the tumor removes the source of antigens and the duration of post-surgery antigen presentation is then limited by the half-life of the remaining antigen-bearing dendritic cells. The initial persistence of cross-presentation in the draining nodes after primary resection suggests a possible window of opportunity for locally delivered immune adjuvant therapy into the resection bed (Pg 1090, left column, both paragraphs).
Thus, regarding claims 1, 4, and 9, Fukaya teaches a method for treating SART2 malignancies comprising administering to a cancer patient a 4 CTL epitope linked polypeptide, wherein one of the polypeptides has a SART2 epitope. Brown teaches that DCs that cross-present tumor antigens decline gradually after tumor resection but could be bolstered by locally delivered immune adjuvant therapy into the resection bed. Therefore, it would be prima facie obvious to treat a SART2 malignant cancer comprising administering a 4 CTL epitope linked polypeptide containing a SART2 epitope to a subject in need thereof following surgery in order to more effectively target such cancers by increasing the number of DCs that recognize the tumor antigen. One skilled in the art would have a reasonable expectation of success as it was already established that post-surgical adjuvant therapy can help modulate the immune system to more effectively treat cancer.
Regarding claims 5 and 6, Fukaya additionally teaches the use of other linkers to connect 4 CTL epitope peptides together, including amino acid linkers such as arginine trimer, arginine tetramer, lysine dimer, lysine trimer, lysine tetramer, glycine dimer, glycine trimer, glycine tetramer, glycine pentamer, glycine hexamer, alanine-alanine-tyrosine (AAY), isoleucine-leucine-alanine (ILA)k, and arginine-valine-lysine-arginine (RVKR), with an arginine dimer or trimer being preferable (Col. 8, lines 39-52).
Regarding claims 10 and 11, Fukaya teaches that the aforementioned peptides are useful in the “treatment and/or prevention of cancer”, which refers to prevention of the development/recurrence of cancer, suppression of the progression/exacerbation of cancer, or the improvement of cancer conditions, thus reading on the use of said peptides to treat tumor recurrence and metastasis.
Regarding claims 12 and 13, Fukaya further discloses embodiments wherein the peptide having 4 linked epitopes may consist of hydrophilic amino acids linked to the N terminus that may be composed of arginine trimer or arginine tetramer composed of three or four arginine residues linked to each other (Col. 4, lines 18-25).
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, 4-6, and 9-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 11, and 13 of U.S. Patent No. US 10,137,183 B2 (‘183; published 11/27/18). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Independent claim 1 of US ‘183 recites a peptide having the general formula: A-(L)-B-(L)-C-(L)-D wherein (L) is a linker and wherein A, B, C, and D consist of a total of four CTL epitope peptides and are independently selected from the group consisting of: PEP1 as represented by SEQ ID NO: 1; PEP2 as represented by SEQ ID NO: 2; PEP4 as represented by SEQ ID NO: 4; PEP5 as represented by SEQ ID NO: 5; PEP6 as represented by SEQ ID NO: 6; PEP7 as represented by SEQ ID NO: 7; PEP8 as represented by SEQ ID NO: 8; PEP9 as represented by SEQ ID NO: 9; PEP10 as represented by SEQ ID NO: 10; PEP13 as represented by SEQ ID NO: 13; PEP15 as represented by SEQ ID NO; 15; PEP17 as represented by SEQ ID NO: 17; and PEP18 as represented by SEQ 18 NO: 18; and wherein
(a) the peptide comprises PEP2 at the C terminus but not when the peptide comprises PEP7 at the N terminus followed by PEP8; or (b) the peptide comprises PEP4 at the C terminus; or (c) the peptide comprises PEP10 at the C terminus; or (d) the peptide comprises PEP5 at the C terminus preceded by PEP6; or (e) the peptide-consists of PEP5, PEP6, PEP9, and PEP18, and wherein the peptide optionally comprises hydrophilic amino acids at the N terminus or C terminus to improve solubility of the peptide.
Dependent claims include wherein the CTL epitope peptides are 4 non-redundant peptides selected from the group consisting of PEP1, PEP2, PEP4, PEP5 , PEP6, PEP7, PEP8, PEP9, PEP10, PEP13, PEP15, PE17, and PEP18 (claim 2); the peptide is selected from the group consisting of: (i) the peptide comprising PEP2 at the C terminus and also 3 CTL epitope peptides selected from the group consisting of PEP1, PEP7, PEP5, and PEP13 but not when the peptide comprises PEP7 at the N terminus followed by PEP8; (ii) the peptide consisting of PEP4 at the C terminus and also PEP5, PEP6, and PEP9; (iii) the peptide consisting of PEP10 at the C terminus and also 3 CTL epitope peptides selected from the group consisting of PEP1, PEP13, PEP15, PEP17, and PEP18; (iv) the peptide consisting of PEP5 at the C terminus preceded by PEP6, also PEP1 and PEP7; and (v) the peptide consisting of PEP9 at the C terminus and also PEP5, PEP6, and PEP18 (claim 3); the ordered arrangement of the peptide from the N terminus is selected from the group consisting of: PEP5-(L)-PEP6-(L)-PEP5-(L)-PEP4 ;PEP9-(L)-PEP5-(L)-PEP6-(L)-PEP4; PEP6-(L)-PEP5-(L)-PEP9-(L)-PEP4; PEP6-(L)-PEP9-(L)-PEP5-(L)-PEP4; PEP9-(L)-PEP6-(L)-PEP5-(L)-PEP4; PEP5-(L)-PEP9-(L)-PEP6-(L) PEP4; PEP1-(L)-PEP7-(L)-PEP8-(L)-PEP2; PEP1-(L)-PEP8-(L)-PEP7-(L)-PEP2; PEP7-(L)-PEP1-(L)-PEP8-(L)-PEP2; PEP8-(L)-PEP7-(L)-PEP1-(L)-PEP2; PEP8-(L)-PEP1-(L)-PEP7-(L)-PEP2; PEP7-(L)-PEP13-(L)-PEP8-(L)-PEP2; PEP8-(L)-PEP 13-(L)-PEP7-(L)-PEP2; PEP13-(L)-PEP7-(L)-PEP8-(L)-PEP2; PEP8-(L)-PEP7-(L)-PEP13-(L)-PEP2; PEP13-(L)-PEP8-(L)-PEP7-(L)-PEP2; PEP13-(L)-PEP15-(L)-PEPI 8-(L)-PEP10 ; PEP 13-(L)-PEP 18-(L)-PEP15-(L)-PEP10; PEP15-(L)-PEP13-(L)-PEP18-(L)-PEP10; PEP15-(L)-PEP18-(L)-PEP13-(L)-PEP10; PEP18-(L)-PEP13-(L)-PEP15-(L)-PEP10; PEP18-(L)-PEP15-(L)-PEP13-(L)-PEP10; PEP1-(L)-PEP15-(L)-PEP18-(L)-PEP10; PEP1-(L)-PEP18-(L)-PEP15-(L)-PEP10; PEP15-(L)-PEP1-(L)-PEP18-(L)-PEP10; PEP15-(L)-PEP18-(L)-PEP1-(L)-PEP10; PEPI 8-(L)-PEP1-(L)-PEP15-(L)-PEP10; PEP18-(L)-PEP15-(L)-PEP1-(L)-PEP10; PEP15-(L)-PEP17-(L)-PEP13-(L)-PEP10; PEP15-(L)-PEP13-(L)-PEP17-(L)-PEP10; PEP17-(L)-PEP15-(L)-PEP13-(L)-PEP10; PEP17-(L) -PEP13-(L)-PEP15-(L)-PEP10; PEP13-(L) -PEP17-(L)-PEP15-(L)-PEP10; PEP13-(L)-PEP15-(L)-PEP17-(L)-PEP10; PEP6-(L)-PEP18-(L)-PEP5-(L)-PEP9; PEP6-(L)-PEP5-(L)-PEP18-(L)-PEP9; PEP1-(L)-PEP7-(L)-PEP6-(L)-PEP5; or PEP7-(L)-PEP1-(L)-PEP6-(L)-PEP5 (claim 4); the linker is an amino acid linker (claim 5); the amino acid linker is an arginine dimer or an arginine trimer (claim 6); the hydrophilic amino acids are located at the N terminus (claim 7); the hydrophilic amino acids comprise an arginine trimer or an arginine tetramer (claim 8); the peptide consist of the amino acid sequence as shown in SEQ ID NO: 22-66 (claim 9); a pharmaceutical composition comprising, as an active ingredient, the peptide according to claim 1 (claim 11); and a method for treating cancer comprising administering to a cancer patient the peptide or the pharmaceutical composition (claim 13).
Claims 1, 4-6, and 9-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, 10-12, and 14 of U.S. Patent No. US 12,251,447 B2 (‘447; published 3/18/25). Although the claims at issue are not identical, they are not patentably distinct from each other because they contain overlapping subject matter.
Independent claim 1 of US ‘447 recites a combined formulation comprising a peptide having 4 linked epitopes comprising 4 CTL epitope peptides linked via linkers and a PD-1 pathway antagonist in combination, wherein the PD-1 pathway antagonist is at least one selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-PD-L2 antibody, wherein the peptide having 4 linked epitopes comprises: the epitope peptide as shown in SEQ ID NO: 5, the epitope peptide as shown in SEQ ID NO: 6, the epitope peptide as shown in SEQ ID NO: 9, and one epitope peptide selected from the group consisting of the epitope peptide as shown in SEQ ID NO: 2, the epitope peptide as shown in SEQ ID NO: 4 and the 15 epitope peptide as shown in SEQ ID NO: 10, at the C terminus wherein the 4 linked epitopes are linked via linkers, wherein the peptide optionally further comprises a peptide sequence consisting of hydrophilic amino acids, wherein the linker is an arginine dimer composed of wherein the linker is an arginine dimer composed of two arginine residues linked to each other, wherein the peptide sequence consisting of hydrophilic amino acids is linked to the N terminus and is composed of an arginine trimer composed of three arginine residues linked to each other or an arginine tetramer composed of four arginine residues linked to each other.
Dependent claims include the combined formulation, wherein the combined formulation comprises a peptide having the sequence of SEQ ID NO: 24, a peptide having the sequence of SEQ ID NO: 44 (instant SEQ ID NO: 29),and a peptide having the sequence of SEQ ID NO: 45 (instant SEQ ID NO: 30; claim 3).
Independent claim 4 recites method for treating a cancer in a patient by administering a peptide having 4 linked epitopes comprising 4 CTL epitope peptides linked via linkers and a PD-1 pathway antagonist, wherein the PD-1 pathway antagonist is at least one selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-PD-L2 antibody, wherein the peptide having 4 linked epitopes comprises: the epitope peptide as shown in SEQ ID NO: 5, the epitope peptide as shown in SEQ ID NO: 6, the epitope peptide as shown in SEQ ID NO: 9, and one epitope peptide selected from the group consisting of the epitope peptide as shown in SEQ ID NO: 2, the epitope peptide as shown in SEQ ID NO: 4 and the epitope peptide as shown in SEQ ID NO: 10, at the C terminus wherein the 4 linked epitopes are linked via linkers, wherein the peptide optionally further comprises a peptide sequence consisting of hydrophilic amino acids, wherein the linker is an arginine dimer composed of two arginine residues linked to teach other, wherein the peptide sequence consisting of hydrophilic amino acids is linked to the N terminus and is composed of an arginine trimer composed of three arginine residues linked to each other or an arginine tetramer composed of four arginine residues linked to each other.
Dependent claims include wherein the peptide having 4 linked epitopes is shown in SEQ ID NO: 24, 25, or 26 (which are identical to the instant SEQ ID NO: 24, 25, and 25; claim 5); the peptide having 4 linked epitopes is administered to the patient before administration of the PD-1 pathway antagonist, simultaneously with administration of the PD-1 pathway antagonist, or after administration of the PD-1 pathway antagonist (claim 8); the method comprising administering to the patient a peptide having the sequence of SEQ ID NO: 24, a peptide having the sequence of SEQ ID NO: 44 (instant SEQ ID NO: 29), and a peptide having the sequence of SEQ ID NO: 45 (instant SEQ ID NO: 30), as a mixture (claim 10).
Independent claim 11 recites a method for enhancing the antitumor effect of a PD-1 pathway antagonist, comprising administering a peptide having 4 linked epitopes to a patient, wherein the PD-1 pathway antagonist is at least one selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, and an anti-PD-L2 antibody, wherein the peptide having 4 linked epitopes comprises: the epitope peptide as shown in SEQ ID NO: 5, the epitope peptide as shown in SEQ ID NO: 6, the epitope peptide as shown in SEQ ID NO: 9, and one epitope peptide selected from the group consisting of the epitope peptide as shown in SEQ ID NO: 2, the epitope peptide as shown in SEQ ID NO: 4 and the epitope peptide as shown in SEQ ID NO: 10, at the C terminus wherein the 4 linked epitopes are linked via linkers, wherein the peptide optionally further comprises a peptide sequence consisting of hydrophilic amino acids, wherein the linker is an arginine dimer composed of two arginine residues linked to each other, wherein the peptide sequence consisting of hydrophilic amino acids is linked to the N terminus and is composed of an arginine trimer composed of three arginine residues linked to each other or an arginine tetramer composed of four arginine residues linked to each other.
Dependent claims include wherein the peptide having 4 linked epitopes is administered to the patient before administration of the PD-1 pathway antagonist, simultaneously with administration of the PD-1 pathway antagonist, or after administration of the PD-1 pathway antagonist (claim 12); and wherein the method comprises administering a peptide having the sequence of SEQ ID NO: 24, a peptide having the sequence of SEQ ID NO: 44, and a peptide having the sequence of SEQ ID NO; 45, as a mixture (claim 14).
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sara E Konopelski Snavely whose telephone number is (571)272-1841. The examiner can normally be reached Monday - Friday 9-6pm EST.
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, Melissa L Fisher can be reached on 571-270-7430. 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.
/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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