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 .
Claims 1-32 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group I, Claims 1-14, in the reply filed on 6/16/2026 is acknowledged.
Claims 1-32 are currently pending.
Claims 15-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/16/2026.
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.
Claims 8-10 and 12 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.
Claims 8 and 9
Claims 8 and 9 recite the limitation "the one or more additional adjuvant” in the body of the claim. There is insufficient antecedent basis for this limitation in the claim.
Note: for examination, liposomes comprising QS21 and/or MPLA adjuvants will be treated as satisfying the limitations of claim 8 and liposomes comprising a MPLA adjuvant or a synthetic variant thereof will be treated as satisfying claim 9.
Claim 12 recites the limitation "the QS21 and PHAD” in the body of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-9, 11 and 13-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lovell (Lovell, et al., US2018/0085473A1; Published 3/29/2018) in view of Mahr (Mahr, et al., US 2017/0342125A1; Published 11/30/2017, of record).
Lovell teaches on the subject of metalloporphyrin-comprising nanostructures, wherein the metalloporphyrin moieties are comprised within a bilayer and associate with His-tag polypeptides embedded within the bilayer (Lovell, Abstract)
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(Lovell, Abstract)
Lovell teaches that one of the challenges associated with functionalized nanoparticles is to easily and reliably attach peptides and proteins to larger scaffolds, with most bioconjugations to nanoparticles suffering from one or more of the following limitations: 1) low conjugated yields and necessitated purification steps, 2) incompatibility with biological buffers making conjugation impossible, 3) variable labeling sites and conjugated polypeptide conformation leading to inhomogeneous particle populations and 4) necessity for complex and exogenous chemical approaches (Lovell, ¶ 0004). Regarding the structural limitations exclusive of the MHCI peptide recited in claims 1-3, Lovell teaches that the nanostructures of Lovell comprise a liposome comprising a phospholipid bilayer with cobalt metalloporphyrin moieties within the interstitial layer of the bilayer that form noncovalent associations with polyhistidine anchored within the interstitial layer of the bilayer (Lovell, ¶ 0007-0010). Lovell teaches that the metalloporphyrin bilayers of the nanostructures of Lovell are functionalized with his-tagged polypeptides as a platform for presentation of such polypeptides to immune cells to foment an immune response against the his-tagged polypeptides (Lovell, ¶ 0034-35). Regarding claim 6, Lovell teaches that the his-tags of Lovell comprise 6-10 histidines (Lovell, ¶ 0038). Regarding claims 7-9, Lovell teaches that the nanostructures of Lovell further comprise an adjuvant that is MPLA (Lovell, ¶ 0059). Regarding claim 13, Lovell teaches administration of the nanostructures of Lovell to humans (Lovell, claim 18). Regarding claim 14, Lovell teaches multiple administrations of the nanostructures of Lovell (Lovell, ¶ 0075). Lovell teaches that the ratio of lipid to any cargo agent is from 10:1 to 5:1 (Lovell, ¶ 0070)
Lovell does not teach that the his-tagged polypeptide of Lovell is a 9 AA MHCI tumor-associated peptide. Lovell does not teach that the ratio of his-tag peptide to adjuvant is 1:1.
Lovell does not teach a method of reducing the growth of a tumor, said method comprising administering the co-metalloporphyrin-his-tagged antigenic peptide sequence liposome delivery system of Lovell with MHC I tumor associated peptide sequences as the his-tagged antigenic peptide to a patient having a tumor, wherein an immune response is elicited against a tumor antigen.
Mahr teaches immunotherapeutics for cancer comprising tumor-associated T cell peptide epitopes (Mahr, Abstract), with SEQ ID NOs:1-3 of Mahr being 9 AA peptides binding MHC I of the HLA-A*02:01 allele (Mahr, ¶ 0415-0417).
It would be prima facie obvious to one of ordinary skill in the art to choose the MHC I-binding tumor-associated peptide epitopes of 9 AAs of Mahr as the polypeptide for the his-tagged polypeptides present in the cobalt metalloporphyrin liposomal antigen presentation nanostructures of Lovell and administer the resultant his-tagged MHC-I tumor T cell epitope peptide-cobalt metalloporphyrin liposomal antigen presentation system in methods of reducing the growth of the tumors associated with the tumor T cell epitope of Mahr, wherein an immune response is generated against a tumor antigen. One of ordinary skill in the art would be motivated to do this in order to better treat cancer. One of ordinary skill in the art would have a reasonable expectation of success choosing the MHC I-binding tumor-associated peptide epitopes of 9 AAs of Mahr as the polypeptide for the his-tagged polypeptides present in the cobalt metalloporphyrin liposomal antigen presentation nanostructures of Lovell and administer the resultant his-tagged MHC-I tumor T cell epitope peptide-cobalt metalloporphyrin liposomal antigen presentation system in methods of reducing the growth of the tumors associated with the tumor T cell epitope of Mahr, wherein an immune response is generated against a tumor antigen because: 1) Lovell teaches that the co-metalloporphyrin nanostructures of Lovell are antigen-presentation systems intended to elicit an immune response against the his-tagged polypeptides, 2) Mahr teaches that each of the MHC I peptides of Mahr is a T cell epitope associated with at least one tumor type and 3) it is within the purview of one of skill in the art to realize that when tumor-associated antigenic peptides are loaded onto an antigen presentation system that the result will be a T cell response being induced against that specific tumor antigen and, as such, will be likely to reduce growth of the associated tumor.
It would be prima facie obvious to one of ordinary skill in the art to start with a ratio of lipid:agent of 10:1-5:1 for both peptide and adjuvant cargo agents taught by Lovell and arrive at a ratio of 1:1 peptide:adjuvant by routine experimentation. One of ordinary skill in the art would be motivated to do this in order to balance the beneficial immunostimulatory effect caused by adjuvant + peptide while minimizing deleterious off-target effects of adjuvant alone. One of ordinary skill in the art would have a reasonable expectation of success starting with ratios of lipid:agent of 10:1-5:1 for both peptide and adjuvant cargo agents taught by Lovell and arriving at a ratio of 1:1 peptide:adjuvant by routine experimentation because routine experimentation is within the purview of one of skill in the art. Additionally, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0); In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (See MPEP 2144.05).
Claim(s) 1-11 and 13-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lovell (Lovell, et al., US2018/0085473A1; Published 3/29/2018) in view of Mahr (Mahr, et al., US 2017/0342125A1; Published 11/30/2017, of record) as applied to claims 1-9, 11 and 13-14 above and in further view of Eldridge (Eldridge, et al., US 2016/0220666A1; Published 8/4/2016).
The teachings of Lovell and Mahr are discussed above.
Lovell and Mahr do not teach that the adjuvant present in the his-tagged MHC-I tumor peptide-co metalloporphyrin liposome antigen presentation system collectively taught by Lovell and Mahr is phosphorylated hexaacyl disaccharide (“PHAD”).
Eldridge teaches on the subject of novel vaccine adjuvants (Eldridge, Abstract). Eldridge teaches that the adjuvant of Eldridge is phosphorylated hexaacyl disaccharide (PHAD) (Eldridge, ¶ 0042), with the PHAD of Eldridge having the advantages of a controlled manufacturing supply and stability when compared to MPL vaccine adjuvants (Eldridge, ¶ 0018).
It would be prima facie obvious to one of ordinary skill in the art to choose the PHAD of Eldridge as the specific adjuvant in the his-tagged MHC-I peptide-co metalloporphyrin vaccine system taught by Lovell and Mahr. One of ordinary skill in the art would be motivated to do this to have a vaccine adjuvant that is stable. One of ordinary skill in the art would have a reasonable expectation of success choosing the PHAD of Eldridge as the specific adjuvant in the his-tagged MHC-I peptide-co metalloporphyrin vaccine system taught by Lovell and Mahr because Lovell teaches that MPL adjuvants are suitable for use in the metalloporphyrin liposome antigen presentation system of Lovell and Eldridge teaches that PHAD adjuvants have the advantage of stability compared to MPL adjuvants.
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 1-9, 11 and 13-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-19 of U.S. Patent No. 12,527,859 B2
claims 1-21 of U.S. Patent No. 11,207,421 B2
and claims 1-21 of U.S. Patent No. 10,272,160 B2
all in view of Lovell (Lovell, et al., US2018/0085473A1; Published 3/29/2018) and Mahr (Mahr, et al., US 2017/0342125A1; Published 11/30/2017, of record).
All of the reference patents above recite liposomal antigen delivery systems with the following properties: 1) a liposomal bilayer comprising co-metalloporphyrin phospholipids, 2) embedded his-tagged comprising 6 to 10 histidines linked to antigenic peptide sequences and 3) an adjuvant that is MPLA.
The reference patents do not teach that the his-tagged antigenic peptide sequence in the co-metalloporphyrin liposomal antigen delivery system of the reference patents is a 9 AA MHCI tumor associated peptide. The reference patents do not teach that the ratio of his-tag peptide to adjuvant is 1:1. The reference patents do not teach a method of reducing the growth of a tumor, said method comprising administering the co-metalloporphyrin-his-tagged antigenic peptide sequence liposome delivery system of the reference patents with MHC I tumor associated peptide sequences as the his-tagged antigenic peptide to a patient having a tumor, wherein an immune response is elicited against a tumor antigen.
Lovell teaches on the subject of metalloporphyrin-comprising nanostructures, wherein the metalloporphyrin moieties are comprised within a bilayer and associate with His-tag polypeptides embedded within the bilayer (Lovell, Abstract)
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(Lovell, Abstract)
Lovell teaches that one of the challenges associated with functionalized nanoparticles is to easily and reliably attach peptides and proteins to larger scaffolds, with most bioconjugations to nanoparticles suffering from one or more of the following limitations: 1) low conjugated yields and necessitated purification steps, 2) incompatibility with biological buffers making conjugation impossible, 3) variable labeling sites and conjugated polypeptide conformation leading to inhomogeneous particle populations and 4) necessity for complex and exogenous chemical approaches (Lovell, ¶ 0004). Regarding the structural limitations exclusive of the MHCI peptide recited in claims 1-3, Lovell teaches that the nanostructures of Lovell comprise a liposome comprising a phospholipid bilayer with cobalt metalloporphyrin moieties within the interstitial layer of the bilayer that form noncovalent associations with polyhistidine anchored within the interstitial layer of the bilayer (Lovell, ¶ 0007-0010). Lovell teaches that the metalloporphyrin bilayers of the nanostructures of Lovell are functionalized with his-tagged polypeptides as a platform for presentation of such polypeptides to immune cells to foment an immune response against the his-tagged polypeptides (Lovell, ¶ 0034-35). Regarding claim 6, Lovell teaches that the his-tags of Lovell comprise 6-10 histidines (Lovell, ¶ 0038). Regarding claims 7-9, Lovell teaches that the nanostructures of Lovell further comprise an adjuvant that is MPLA (Lovell, ¶ 0059). Regarding claim 13, Lovell teaches administration of the nanostructures of Lovell to humans (Lovell, claim 18). Regarding claim 14, Lovell teaches multiple administrations of the nanostructures of Lovell (Lovell, ¶ 0075). Lovell teaches that the ratio of lipid to any cargo agent is from 10:1 to 5:1 (Lovell, ¶ 0070)
Mahr teaches immunotherapeutics for cancer comprising tumor-associated T cell peptide epitopes (Mahr, Abstract), with SEQ ID NOs:1-3 of Mahr being 9 AA peptides binding MHC I of the HLA-A*02:01 allele (Mahr, ¶ 0415-0417).
It would be prima facie obvious to one of ordinary skill in the art to choose the MHC I-binding tumor-associated peptide epitopes of 9 AAs of Mahr as the polypeptide for the his-tagged polypeptides present in the cobalt metalloporphyrin liposomal antigen presentation nanostructures of the reference patents and administer the resultant his-tagged MHC-I tumor T cell epitope peptide-cobalt metalloporphyrin liposomal antigen presentation system in methods of reducing the growth of the tumors associated with the tumor T cell epitope of Mahr, wherein an immune response is generated against a tumor antigen in view of the teachings of Lovell. One of ordinary skill in the art would be motivated to do this in order to better treat cancer. One of ordinary skill in the art would have a reasonable expectation of success choosing the MHC I-binding tumor-associated peptide epitopes of 9 AAs of Mahr as the polypeptide for the his-tagged polypeptides present in the cobalt metalloporphyrin liposomal antigen presentation nanostructures of the reference patents and administer the resultant his-tagged MHC-I tumor T cell epitope peptide-cobalt metalloporphyrin liposomal antigen presentation system in methods of reducing the growth of the tumors associated with the tumor T cell epitope of Mahr, wherein an immune response is generated against a tumor antigen in view of Lovell because: 1) Lovell teaches that the co-metalloporphyrin nanostructures of the reference patents are antigen-presentation systems intended to elicit an immune response against the his-tagged polypeptides, 2) Mahr teaches that each of the MHC I peptides of Mahr is a T cell epitope associated with at least one tumor type and 3) it is within the purview of one of skill in the art to realize that when tumor-associated antigenic peptides are loaded onto an antigen presentation system that the result will be a T cell response being induced against that specific tumor antigen and, as such, will be likely to reduce growth of the associated tumor.
It would be prima facie obvious to one of ordinary skill in the art to start with a ratio of lipid:agent of 10:1-5:1 for both peptide and adjuvant cargo agents taught by Lovell and arrive at a ratio of 1:1 peptide:adjuvant ratio in the liposomal delivery systems of the reference patents by routine experimentation. One of ordinary skill in the art would be motivated to do this in order to balance the beneficial immunostimulatory effect caused by adjuvant + peptide while minimizing deleterious off-target effects of adjuvant alone. One of ordinary skill in the art would have a reasonable expectation of success starting with ratios of lipid:agent of 10:1-5:1 for both peptide and adjuvant cargo agents taught by Lovell and arriving at a ratio of 1:1 peptide:aduvant in the liposomal delivery systems of the reference patents by routine experimentation because routine experimentation is within the purview of one of skill in the art. Additionally, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0); In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (See MPEP 2144.05).
Claims 1-11 and 13-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-19 of U.S. Patent No. 12,527,859 B2
claims 1-21 of U.S. Patent No. 11,207,421 B2
and claims 1-21 of U.S. Patent No. 10,272,160 B2
all in view of Lovell (Lovell, et al., US2018/0085473A1; Published 3/29/2018) and Mahr (Mahr, et al., US 2017/0342125A1; Published 11/30/2017, of record) as applied to claims 1-9, 11 and 13-14 above and in further view of Eldridge (Eldridge, et al., US 2016/0220666A1; Published 8/4/2016).
The combined teachings of the reference patents, Lovell and Mahr are discussed above.
The reference patents, Lovell and Mahr do not teach that the adjuvant present in the his-tagged MHC-I tumor peptide-co metalloporphyrin liposome antigen presentation system collectively taught by the reference patents, Lovell and Mahr is phosphorylated hexaacyl disaccharide (“PHAD”).
Eldridge teaches on the subject of novel vaccine adjuvants (Eldridge, Abstract). Eldridge teaches that the adjuvant of Eldridge is phosphorylated hexaacyl disaccharide (PHAD) (Eldridge, ¶ 0042), with the PHAD of Eldridge having the advantages of a controlled manufacturing supply and stability when compared to MPL vaccine adjuvants (Eldridge, ¶ 0018).
It would be prima facie obvious to one of ordinary skill in the art to choose the PHAD of Eldridge as the specific adjuvant in the his-tagged MHC-I peptide-co metalloporphyrin vaccine system taught by the reference patents, Lovell and Mahr. One of ordinary skill in the art would be motivated to do this to have a vaccine adjuvant that is stable. One of ordinary skill in the art would have a reasonable expectation of success choosing the PHAD of Eldridge as the specific adjuvant in the his-tagged MHC-I peptide-co metalloporphyrin vaccine system taught by the reference patents, Lovell and Mahr because Lovell teaches that MPL adjuvants are suitable for use in the metalloporphyrin liposome antigen presentation system of the reference patents and Eldridge teaches that PHAD adjuvants have the advantage of stability compared to MPL adjuvants.
Claims 1-9, 11 and 13-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-18 of copending Application No. 18/495,475
claims 1-41 of copending Application No. 18/247,235
all in view of Lovell (Lovell, et al., US2018/0085473A1; Published 3/29/2018) and Mahr (Mahr, et al., US 2017/0342125A1; Published 11/30/2017, of record).
all of the reference applications above recite liposomal antigen delivery systems with the following properties: 1) a liposomal bilayer comprising co-metalloporphyrin phospholipids, 2) embedded his-tagged comprising 6 to 10 histidines linked to antigenic peptide sequences and 3) an adjuvant that is MPLA.
The reference applications do not teach that the his-tagged antigenic peptide sequence in the co-metalloporphyrin liposomal antigen delivery system of the reference applications is a 9 AA MHCI tumor associated peptide. The reference applications do not teach that the ratio of his-tag peptide to adjuvant is 1:1. The reference applications do not teach a method of reducing the growth of a tumor, said method comprising administering the co-metalloporphyrin-his-tagged antigenic peptide sequence liposome delivery system of the reference applications with MHC I tumor associated peptide sequences as the his-tagged antigenic peptide to a patient having a tumor, wherein an immune response is elicited against a tumor antigen.
Lovell teaches on the subject of metalloporphyrin-comprising nanostructures, wherein the metalloporphyrin moieties are comprised within a bilayer and associate with His-tag polypeptides embedded within the bilayer (Lovell, Abstract)
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(Lovell, Abstract)
Lovell teaches that one of the challenges associated with functionalized nanoparticles is to easily and reliably attach peptides and proteins to larger scaffolds, with most bioconjugations to nanoparticles suffering from one or more of the following limitations: 1) low conjugated yields and necessitated purification steps, 2) incompatibility with biological buffers making conjugation impossible, 3) variable labeling sites and conjugated polypeptide conformation leading to inhomogeneous particle populations and 4) necessity for complex and exogenous chemical approaches (Lovell, ¶ 0004). Regarding the structural limitations exclusive of the MHCI peptide recited in claims 1-3, Lovell teaches that the nanostructures of Lovell comprise a liposome comprising a phospholipid bilayer with cobalt metalloporphyrin moieties within the interstitial layer of the bilayer that form noncovalent associations with polyhistidine anchored within the interstitial layer of the bilayer (Lovell, ¶ 0007-0010). Lovell teaches that the metalloporphyrin bilayers of the nanostructures of Lovell are functionalized with his-tagged polypeptides as a platform for presentation of such polypeptides to immune cells to foment an immune response against the his-tagged polypeptides (Lovell, ¶ 0034-35). Regarding claim 6, Lovell teaches that the his-tags of Lovell comprise 6-10 histidines (Lovell, ¶ 0038). Regarding claims 7-9, Lovell teaches that the nanostructures of Lovell further comprise an adjuvant that is MPLA (Lovell, ¶ 0059). Regarding claim 13, Lovell teaches administration of the nanostructures of Lovell to humans (Lovell, claim 18). Regarding claim 14, Lovell teaches multiple administrations of the nanostructures of Lovell (Lovell, ¶ 0075). Lovell teaches that the ratio of lipid to any cargo agent is from 10:1 to 5:1 (Lovell, ¶ 0070)
Mahr teaches immunotherapeutics for cancer comprising tumor-associated T cell peptide epitopes (Mahr, Abstract), with SEQ ID NOs:1-3 of Mahr being 9 AA peptides binding MHC I of the HLA-A*02:01 allele (Mahr, ¶ 0415-0417).
It would be prima facie obvious to one of ordinary skill in the art to choose the MHC I-binding tumor-associated peptide epitopes of 9 AAs of Mahr as the polypeptide for the his-tagged polypeptides present in the cobalt metalloporphyrin liposomal antigen presentation nanostructures of the reference applications and administer the resultant his-tagged MHC-I tumor T cell epitope peptide-cobalt metalloporphyrin liposomal antigen presentation system in methods of reducing the growth of the tumors associated with the tumor T cell epitope of Mahr, wherein an immune response is generated against a tumor antigen in view of the teachings of Lovell. One of ordinary skill in the art would be motivated to do this in order to better treat cancer. One of ordinary skill in the art would have a reasonable expectation of success choosing the MHC I-binding tumor-associated peptide epitopes of 9 AAs of Mahr as the polypeptide for the his-tagged polypeptides present in the cobalt metalloporphyrin liposomal antigen presentation nanostructures of the reference applications and administer the resultant his-tagged MHC-I tumor T cell epitope peptide-cobalt metalloporphyrin liposomal antigen presentation system in methods of reducing the growth of the tumors associated with the tumor T cell epitope of Mahr, wherein an immune response is generated against a tumor antigen in view of Lovell because: 1) Lovell teaches that the co-metalloporphyrin nanostructures of the reference applications are antigen-presentation systems intended to elicit an immune response against the his-tagged polypeptides, 2) Mahr teaches that each of the MHC I peptides of Mahr is a T cell epitope associated with at least one tumor type and 3) it is within the purview of one of skill in the art to realize that when tumor-associated antigenic peptides are loaded onto an antigen presentation system that the result will be a T cell response being induced against that specific tumor antigen and, as such, will be likely to reduce growth of the associated tumor.
It would be prima facie obvious to one of ordinary skill in the art to start with a ratio of lipid:agent of 10:1-5:1 for both peptide and adjuvant cargo agents taught by Lovell and arrive at a ratio of 1:1 peptide:adjuvant ratio in the liposomal delivery systems of the reference applications by routine experimentation. One of ordinary skill in the art would be motivated to do this in order to balance the beneficial immunostimulatory effect caused by adjuvant + peptide while minimizing deleterious off-target effects of adjuvant alone. One of ordinary skill in the art would have a reasonable expectation of success starting with ratios of lipid:agent of 10:1-5:1 for both peptide and adjuvant cargo agents taught by Lovell and arriving at a ratio of 1:1 peptide:aduvant in the liposomal delivery systems of the reference applications by routine experimentation because routine experimentation is within the purview of one of skill in the art. Additionally, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0); In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (See MPEP 2144.05).
This is a provisional nonstatutory double patenting rejection.
Claims 1-9, 11 and 13-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 1-18 of copending Application No. 18/495,475
claims 1-41 of copending Application No. 18/247,235
all in view of Lovell (Lovell, et al., US2018/0085473A1; Published 3/29/2018) and Mahr (Mahr, et al., US 2017/0342125A1; Published 11/30/2017, of record) as applied to claims 1-9, 11 and 13-14 above and in further view of Eldridge (Eldridge, et al., US 2016/0220666A1; Published 8/4/2016).
The combined teachings of the reference applications, Lovell and Mahr are discussed above.
The reference applications, Lovell and Mahr do not teach that the adjuvant present in the his-tagged MHC-I tumor peptide-co metalloporphyrin liposome antigen presentation system collectively taught by the reference applications, Lovell and Mahr is phosphorylated hexaacyl disaccharide (“PHAD”).
Eldridge teaches on the subject of novel vaccine adjuvants (Eldridge, Abstract). Eldridge teaches that the adjuvant of Eldridge is phosphorylated hexaacyl disaccharide (PHAD) (Eldridge, ¶ 0042), with the PHAD of Eldridge having the advantages of a controlled manufacturing supply and stability when compared to MPL vaccine adjuvants (Eldridge, ¶ 0018).
It would be prima facie obvious to one of ordinary skill in the art to choose the PHAD of Eldridge as the specific adjuvant in the his-tagged MHC-I peptide-co metalloporphyrin vaccine system taught by the reference applications, Lovell and Mahr. One of ordinary skill in the art would be motivated to do this to have a vaccine adjuvant that is stable. One of ordinary skill in the art would have a reasonable expectation of success choosing the PHAD of Eldridge as the specific adjuvant in the his-tagged MHC-I peptide-co metalloporphyrin vaccine system taught by the reference applications, Lovell and Mahr because Lovell teaches that MPL adjuvants are suitable for use in the metalloporphyrin liposome antigen presentation system of the reference applications and Eldridge teaches that PHAD adjuvants have the advantage of stability compared to MPL adjuvants.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/SYDNEY VAN DRUFF/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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