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 1-19 are pending and are under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/26/2025 has been considered by the examiner.
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:
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.
Claim(s) 1-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Datoo M, Natama M, Somé A et al (“Datoo”). Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. The Lancet, 2021; 397, 1809-1818 as evidenced by Carnot et al.(“Carnot”) Front Drug Deliv. 2023 Nov 6; 3:1279710. doi: 10.3389/fddev.2023.1279710, cited in IDS.
Claim 1: Datoo disclose a method of providing a vaccination composition to a children subjects aged 5-17 months, comprising:
injecting the vaccination composition at an intramuscular injection into the thigh (p. 1811 1st paragraph under procedures and p. 1816 3rd paragraph “pain at injection site) of the subject, the vaccination composition comprising a saponin-based adjuvant Matrix-M™ (MM) and malaria antigen R21 and the thigh being associated with a draining lymph node (dLN). See abstract and p. 1811 under study designs and a participants and under procedures.
Since the method step of administering is the same then it follows the same results will be effected i.e. following injection of the vaccination composition at the intramuscular injection site, a fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant has a minimum value at a time greater than one hour following injection of the vaccination composition at the intramuscular injection site and less than 24 hours following injection of the vaccination composition at the intramuscular injection site, the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant at a time 24 hours following injection of the vaccination composition having a value greater than the minimum value.
Claim 2: Since the method step of administering is the same then it follows the same results will be effected i.e. the minimum value is more than about one tenth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
Claim 3: Since the method step of administering is the same then it follows the same results will be effected i.e. the minimum value is more than about one eighth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
Claim 4: Since the method step of administering is the same then it follows the same results will be effected i.e. the minimum value is more than about one fifth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
Claim 5: As evidenced by Carnot Matrix-M™ adjuvant is a saponin-based adjuvant, made with saponins from the Chilean soap bark tree (Quillaja saponaria Molina) that are formulated with cholesterol and phospholipids into cage-like nanoparticles and the two types of such nanoparticles, Matrix-A™ and Matrix-C™, each made up with a specific saponin fraction (Fraction-A; Fr-A, and Fraction-C; Fr-C), are mixed at a set ratio to form Matrix-M™ adjuvant and the main component is Matrix-A™, which comprises 85% of Matrix-M™. See under introduction.
Claim 6: the mammalian subject is a human. See abstract.
Claim 7: the saponin-based MM adjuvant is mixed with an R21 antigen. See abstract.
Claim 8: the saponin-based MM adjuvant is necessarily mixed with a carrier as the components do not exist in a vacuum. Especially, when the children were immunized intramuscularly by injection with the mixture of the saponin adjuvant and the antigen. See abstract and p. 1811 under study designs and a participants and under procedures.
Claim 9: Datoo disclose a method of providing a vaccination composition to a children subjects aged 5-17 months, comprising:
injecting the vaccination composition at an intramuscular injection into the thigh (p. 1811 1st paragraph under procedures and p. 1816 3rd paragraph “pain at injection site) of the subject, the vaccination composition comprising a saponin-based adjuvant Matrix-M™ (MM) and malaria antigen R21 and the thigh being associated with a draining lymph node (dLN). See abstract and p. 1811 under study designs and a participants and under procedures.
Since the method step of administering is the same then it follows the same results will be effected i.e. over a time period between about one hour and about twenty four hours following injection of the vaccination composition, a fraction of B cells in the dLN that are positive for i) CD45 and ii) the adjuvant has a maximum value at a time less than three hours following injection of the mixture at the intramuscular injection site.
Claim 10: Since the method step of administering is the same then it follows the same results will be effected i.e. a value of the fraction of B cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one tenth of the maximum value.
Claim 11: Since the method step of administering is the same then it follows the same results will be effected i.e. a value of the fraction of cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one twentieth of the maximum value.
Claim 12: As evidenced by Carnot the saponin-based adjuvant comprises nanoparticles of Q. saponaria saponin fraction A, cholesterol and phospholipid and nanoparticles of Q. saponaria saponin fraction C, cholesterol and phospholipid.
Claim 13: the mammalian subject is a human as set forth above.
Claim 14: The saponin-based adjuvant is mixed with an R21 antigen as set forth above.
Claim 15: the saponin-based adjuvant is necessarily mixed with a carrier as set forth above.
Claim 16: Datoo disclose a method of providing a vaccination composition to a children subjects aged 5-17 months, comprising:
injecting the vaccination composition at an intramuscular injection into the thigh (p. 1811 1st paragraph under procedures and p. 1816 3rd paragraph “pain at injection site) of the subject, the vaccination composition comprising a saponin-based adjuvant Matrix-M™ (MM) and malaria antigen R21 and the thigh being associated with a draining lymph node (dLN). See abstract and p. 1811 under study designs and a participants and under procedures. As evidenced by Carnot, MM adjuvant comprises cholesterol and phospholipid.
Since the method step of administering is the same then it follows the same results will be effected i.e. following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's blood plasma peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's blood plasma peaks at a time greater than 6 hours after the injection.
Claim 17: The MM saponin-based adjuvant comprises nanoparticles of Q. saponaria saponin fraction A, cholesterol and phospholipid and nanoparticles of Q. saponaria saponin fraction C, cholesterol and phospholipid as evidenced by Carnot.
Claim 18: the saponin-based adjuvant is necessarily mixed with a carrier as set forth above.
Claim 19: Since the method step of administering is the same then it follows the same results will be effected i.e. following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's kidney peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's kidney peaks at a time greater than 24 hours after the injection.
Claim(s) 1-5 and 14-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Carnot et al.(“Carnot”) Front Drug Deliv. 2023 Nov 6; 3:1279710. doi: 10.3389/fddev.2023.1279710, cited in IDS.
Claim 1: Carnot disclose method of providing a vaccination composition to a mammalian subject (mice), comprising: injecting the vaccination composition at an intramuscular injection site of the subject, the vaccination composition comprising a saponin-based adjuvant (radiolabeled saponins or cholesterol were incorporated into Matrix-A™ particles, which represent 85% of Matrix-M™ and labeled Matrix-M™ adjuvant was given to mice by intramuscular injection with or without SARS-CoV-2 Spike protein) and the intramuscular injection site being associated with a draining lymph node (dLN) (radioactivity of the adjuvant components was quantified in local and systemic tissues at seven timepoints over a period of 1–168 h and the highest saponin levels were found at the 1-h timepoint at the injection site, in the draining (iliac) lymph nodes, and in urine). See title and abstract.
Since the method step of administering is the same then it follows the same results will be effected i.e. following intramuscular injection of the same vaccination composition (vaccine composition comprising a saponin-based adjuvant) at the intramuscular injection site, a fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant has a minimum value at a time greater than one hour following injection of the vaccination composition at the intramuscular injection site and less than 24 hours following injection of the vaccination composition at the intramuscular injection site, the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant at a time 24 hours following injection of the vaccination composition having a value greater than the minimum value.
Claim 2: Since the method step of administering is the same then it follows the same results will be effected i.e. continued from claim 1 the minimum value is more than about one tenth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
Claim 3: Since the method step of administering is the same then it follows the same results will be effected i.e. continued from claim 1, the minimum value is more than about one eighth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
Claim 4: Since the method step of administering is the same then it follows the same results will be effected i.e. continued from claim 1, the minimum value is more than about one fifth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
Claim 5: Carnot et al disclose the saponin-based adjuvant comprises nanoparticles of Q. saponaria saponin fraction A, cholesterol and phospholipid and nanoparticles of Q. saponaria saponin fraction C, cholesterol and phospholipid: Matrix-M™ adjuvant is a saponin-based adjuvant, made with saponins from the Chilean soap bark tree (Quillaja saponaria Molina) that are formulated with cholesterol and phospholipids into cage-like nanoparticles and the two types of such nanoparticles, Matrix-A™ and Matrix-C™, each made up with a specific saponin fraction (Fraction-A; Fr-A, and Fraction-C; Fr-C), are mixed at a set ratio to form Matrix-M™ adjuvant and the main component is Matrix-A™, which comprises 85% of Matrix-M™. See under introduction.
Claim 7: Carnot et al disclose the saponin-based adjuvant is mixed with an SARS-CoV-2 virus antigen. See abstract.
Claim 8: the saponin-based adjuvant is necessarily mixed with a carrier as the components do not exist in a vacuum. Especially, when the mice were immunized intramuscularly by injection with the mixture of the saponin adjuvant and the antigen. See section 2.2 Biodistribution. The injection mixture necessarily comprises a carrier.
Claim 9: Carnot disclose method of providing a vaccination composition to a mammalian subject (mice), comprising: injecting the vaccination composition at an intramuscular injection site of the subject, the vaccination composition comprising a saponin-based adjuvant (radiolabeled saponins or cholesterol were incorporated into Matrix-A™ particles, which represent 85% of Matrix-M™ and labeled Matrix-M™ adjuvant was given to mice by intramuscular injection with or without SARS-CoV-2 Spike protein) and the intramuscular injection site being associated with a draining lymph node (dLN) (radioactivity of the adjuvant components was quantified in local and systemic tissues at seven timepoints over a period of 1–168 h and the highest saponin levels were found at the 1-h timepoint at the injection site, in the draining (iliac) lymph nodes, and in urine). See title and abstract.
Since the method step of administering is the same then it follows the same results will be effected i.e. over a time period between about one hour and about twenty four hours following injection of the vaccination composition, a fraction of B cells in the dLN that are positive for i) CD45 and ii) the adjuvant has a maximum value at a time less than three hours following injection of the mixture at the intramuscular injection site.
Claim 10: Since the method step of administering is the same then it follows the same results will be effected i.e. continued from claim 9, a value of the fraction of B cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one tenth of the maximum value.
Claim 11: Since the method step of administering is the same then it follows the same results will be effected i.e. continued from claim 9, a value of the fraction of cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one twentieth of the maximum value.
Claim 12: Carnot et al disclose the Matrix-M™ adjuvant is a saponin-based adjuvant, made with saponins from the Chilean soap bark tree (Quillaja saponaria Molina) that are formulated with cholesterol and phospholipids into cage-like nanoparticles and the two types of such nanoparticles, Matrix-A™ and Matrix-C™, each made up with a specific saponin fraction (Fraction-A; Fr-A, and Fraction-C; Fr-C), are mixed at a set ratio to form Matrix-M™ adjuvant and the main component is Matrix-A™, which comprises 85% of Matrix-M™. See under introduction.
Claim 14: Carnot et al disclose the saponin-based adjuvant is mixed with an SARS-CoV-2 virus antigen. See abstract.
Claim 15: the saponin-based adjuvant is necessarily mixed with a carrier as the components do not exist in a vacuum. Especially, when the mice were immunized intramuscularly by injection with the mixture of the saponin adjuvant and the antigen. See section 2.2 Biodistribution. The injection mixture necessarily comprises a carrier.
Claim 16: Carnot disclose method of providing a vaccination composition to a mammalian subject (mice), comprising: injecting the vaccination composition at an intramuscular injection site of the subject, the vaccination composition comprising a saponin-based adjuvant (radiolabeled saponins or cholesterol were incorporated into Matrix-A™ particles, which represent 85% of Matrix-M™ (Matrix-M™ comprises saponin amd cholesterol) and labeled Matrix-M™ adjuvant was given to mice by intramuscular injection with or without SARS-CoV-2 Spike protein) and the intramuscular injection site being associated with a draining lymph node (dLN) (radioactivity of the adjuvant components was quantified in local and systemic tissues at seven timepoints over a period of 1–168 h and the highest saponin levels were found at the 1-h timepoint at the injection site, in the draining (iliac) lymph nodes, and in urine). See title and abstract and introduction.
Since the method step of administering is the same then it follows the same results will be effected i.e. following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's blood plasma peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's blood plasma peaks at a time greater than 6 hours after the injection.
Claim 17: Carnot et al disclose the Matrix-M™ adjuvant is a saponin-based adjuvant, made with saponins from the Chilean soap bark tree (Quillaja saponaria Molina) that are formulated with cholesterol and phospholipids into cage-like nanoparticles and the two types of such nanoparticles, Matrix-A™ and Matrix-C™, each made up with a specific saponin fraction (Fraction-A; Fr-A, and Fraction-C; Fr-C), are mixed at a set ratio to form Matrix-M™ adjuvant and the main component is Matrix-A™, which comprises 85% of Matrix-M™. See under introduction.
Claim 18: the saponin-based adjuvant is necessarily mixed with a carrier as the components do not exist in a vacuum. Especially, when the mice were immunized intramuscularly by injection with the mixture of the saponin adjuvant and the antigen. See section 2.2 Biodistribution. The injection mixture necessarily comprises a carrier.
Claim 19: Since the method step of administering is the same then it follows the same results will be effected i.e. continued from claim 16, wherein, following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's kidney peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's kidney peaks at a time greater than 24 hours after the injection.
Claim(s) 1-19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stertman et al. (“Stertman”) The Matrix-MTM adjuvant: A critical component of vaccines for the 21st century. Human Vaccines & Immunotherapeutics, 19(1). https://doi.org/10.1080/21645515.2023.2189885, cited in IDS.
Claim 1: Stertman et al disclose a method of providing a vaccination composition to a mammalian subject, comprising: injecting the vaccination composition at an intramuscular injection site of the subject, the vaccination composition comprising a saponin-based adjuvant and the intramuscular injection site being associated with a draining lymph node (dLN): injection of Matrix-M™-adjuvanted vaccine into the muscle leads to a transient recruitment and activation of innate immune cells, including antigen-presenting cells, at the injection site. The presence of Matrix-M facilitates antigen uptake and transport to the draining lymph nodes. See figure 1 and legend: “proposed Matrix-M™ adjuvant mechanism of action.
Since the method step of administering is the same then it follows the same results will be effected i.e. following injection of the vaccination composition at the intramuscular injection site, a fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant has a minimum value at a time greater than one hour following injection of the vaccination composition at the intramuscular injection site and less than 24 hours following injection of the vaccination composition at the intramuscular injection site, the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant at a time 24 hours following injection of the vaccination composition having a value greater than the minimum value.
Claim 2: Since the method step of administering is the same then it follows the same results will be effected i.e. the minimum value is more than about one tenth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
Claim 3: Since the method step of administering is the same then it follows the same results will be effected i.e. the minimum value is more than about one eighth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
Claim 4: Since the method step of administering is the same then it follows the same results will be effected i.e. the minimum value is more than about one fifth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
Claim 5: Stertman et al discloses the Matrix-M™ adjuvant consists of two distinct fractions of saponins purified from the Quillaja saponaria Molina tree, combined with cholesterol and phospholipids to form 40-nm open cage-like nanoparticles. Stertman et al disclose the Matrix-M™ adjuvant consists of two different populations of physically stable nanoparticles mixed at a defined ratio (85% Matrix-A + 15% Matrix-C). Matrix-A™ and Matrix-C™ contain different Q. saponaria saponin fractions with complementary properties. Matrix-C particles contain Fraction-C saponins (mainly consisting of QS-21), which have strong adjuvant activity but are reactogenic in mice, as measured by lethargy and lethality. Matrix-A particles contain Fraction-A saponins, which have a weaker adjuvant activity than Fraction-C at the same doses but are better tolerated in mice. A combination of these two types of particles was tested. See under abstract and under a brief history of saponin based adjuvants.
Claim 6: Stertman et al disclose indeed, specific CD8+ T-cell responses have been demonstrated in both mice and humans upon vaccination with Matrix-M™-adjuvanted NVX-CoV23737. See under activation of antigen-presenting cells and cross-presentation on page 5 and table 1 page 3.
Claim 7: The method of claim 1, wherein the saponin-based adjuvant is mixed with an antigen e.g. SARS CoV-2 antigen NVX-CoV23737 (See under activation of antigen-presenting cells and cross-presentation); malaria antigen (R21 was combined with Matrix-M™ for clinical development. In a phase 2a trial conducted in the UK using controlled human malaria infection in healthy adults, 3 doses of R21/Matrix-M™ given 4 weeks apart demonstrated high sterile efficacy (81.8%; n = 11) in the prevention of P. falciparum parasitemia); influenza antigen; and Ebola virus antigen etc. See table 1 page 3 and page 7-9.
Claim 8: The Matrix-M™ adjuvant is necessarily mixed with a carrier at formulation or when mixed with the vaccine antigens. Matrix-M™ adjuvant and the Matrix-M™ adjuvant/antigen does not exist in a vacuum but in a carrier for the purposes for vaccine administration such as the clinical trials disclosed in table 1, page 3.
Claim 9. Stertman et al disclose a method of providing a vaccination composition to a mammalian subject, comprising: injecting the vaccination composition at an intramuscular injection site of the subject, the vaccination composition comprising a saponin-based adjuvant and the intramuscular injection site being associated with a draining lymph node (dLN): injection of Matrix-M™-adjuvanted vaccine into the muscle leads to a transient recruitment and activation of innate immune cells, including antigen-presenting cells, at the injection site. The presence of Matrix-M facilitates antigen uptake and transport to the draining lymph nodes. See figure 1 and legend: “proposed Matrix-M™ adjuvant mechanism of action.
Since the method step of administering is the same then it follows the same results will be effected i.e. over a time period between about one hour and about twenty four hours following injection of the vaccination composition, a fraction of B cells in the dLN that are positive for i) CD45 and ii) the adjuvant has a maximum value at a time less than three hours following injection of the mixture at the intramuscular injection site.
Claim 10: Since the method step of administering is the same then it follows the same results will be effected i.e. a value of the fraction of B cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one tenth of the maximum value.
Claim 11: Since the method step of administering is the same then it follows the same results will be effected i.e. a value of the fraction of cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one twentieth of the maximum value.
Claim 12: Stertman as set forth above discloses the saponin-based Matrix-M™ adjuvant comprises nanoparticles of Q. saponaria saponin fraction A, cholesterol and phospholipid and nanoparticles of Q. saponaria saponin fraction C, cholesterol and phospholipid.
Claim 13: Stertman as set forth above discloses the mammalian subject is a human.
Claim 14: Stertman as set forth above discloses the saponin-based adjuvant is mixed with an antigen.
Claim 15: The Matrix-M™ adjuvant is necessarily mixed with a carrier at formulation or when mixed with the vaccine antigens. Matrix-M™ adjuvant and the Matrix-M™ adjuvant/antigen does not exist in a vacuum but in a carrier for the purposes for vaccine administration such as the clinical trials disclosed in table 1, page 3.
Claim 16. Stertman et al disclose a method of providing a vaccination composition to a mammalian subject, comprising: injecting the vaccination composition at an intramuscular injection site of the subject, the vaccination composition comprising a saponin-based adjuvant and the intramuscular injection site being associated with a draining lymph node (dLN): injection of Matrix-M™( Matrix-M™ comprising saponin fractions mixed with both cholesterol and lipid) adjuvanted vaccine (the vaccine comprising antigen) into the muscle leads to a transient recruitment and activation of innate immune cells, including antigen-presenting cells, at the injection site. The presence of Matrix-M facilitates antigen uptake and transport to the draining lymph nodes. See figure 1 and legend: “proposed Matrix-M™ adjuvant mechanism of action and table 1 disclosing Matrix-M™ adjuvanted vaccines in clinical trials.
Since the method step of administering is the same then it follows the same results will be effected i.e. following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's blood plasma peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's blood plasma peaks at a time greater than 6 hours after the injection.
Claim 17: Stertman et al disclose as set forth above the saponin-based adjuvant comprises nanoparticles of Q. saponaria saponin fraction A, cholesterol and phospholipid and nanoparticles of Q. saponaria saponin fraction C, cholesterol and phospholipid.
Claim 18: The Matrix-M™ adjuvant is necessarily mixed with a carrier at formulation or when mixed with the vaccine antigens. Matrix-M™ adjuvant and the Matrix-M™ adjuvant/antigen does not exist in a vacuum but in a carrier for the purposes for vaccine administration such as the clinical trials disclosed in table 1, page 3.
Claim 19: Since the method step of administering is the same then it follows the same results will be effected i.e. following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's kidney peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's kidney peaks at a time greater than 24 hours after the injection.
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.
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Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 11253585 (‘585) in view of Smith et al. U.S. Patent No. 11253585 02/22/2022.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘585 claims disclose:
1: A method of providing a vaccination composition to a mammalian subject such as an adult, a senior adult, a pregnant female adult, a child, a neonate, and an infant (claim 6),
, comprising: administering the vaccination composition at an intramuscular site of the subject, the vaccination composition comprising a saponin-based adjuvant comprising at least two iscom particles, wherein: the first iscom particle comprises fraction A of Quillaja Saponaria Molina and not fraction C f Quillaja Saponaria Molina; and the second iscom particle comprises fraction C of Quillaja Saponaria Molina and not fraction A of Quillaja Saponaria Molina.
6. The method of claim 1, wherein the mammalian subject is a human adult, a senior adult, a pregnant female adult, a child, a neonate, and an infant (claim 6),
7. The method of claim 1, wherein the saponin-based adjuvant is mixed with RSV F glycoprotein (claim 1).
8. The method of claim 1, wherein the saponin-based adjuvant is mixed with a carrier.
9. A method of providing a vaccination composition to a mammalian subject, comprising: administering the vaccination composition at an intramuscular site of the subject, the vaccination composition including a saponin-based adjuvant;
12: The ’585 claims disclose the adjuvant comprises at least two iscom particles, wherein: the first iscom particle comprises fraction A of Quillaja Saponaria Molina and not fraction C of Quillaja Saponaria Molina; and the second iscom particle comprises fraction C of Quillaja Saponaria Molina and not fraction A of Quillaja Saponaria Molina (see claim 8).
13: The ’585 claims disclose the mammalian subject is a human adult, a senior adult, a pregnant female adult, a child, a neonate, and an infant (claim 6),
14: The ’585 claims disclose the saponin-based adjuvant is mixed with an RSV F glycoprotein (claim 1).
15: The method of claim 9, wherein the saponin-based adjuvant is mixed with a carrier i.e. a pharmaceutically acceptable carrier. See claim 1 and claim 25.
16: The ’585 claims disclose a method for administering a vaccination composition to a mammalian subject, comprising: administering the vaccination composition at an intramuscular site of the subject; wherein the vaccination composition comprises an RSV antigen and a saponin-based adjuvant, the saponin-based adjuvant (see claim 8) comprising a saponin component;
17. The ’585 claims disclose the adjuvant comprises at least two iscom particles, wherein: the first iscom particle comprises fraction A of Quillaja Saponaria Molina and not fraction C of Quillaja Saponaria Molina; and the second iscom particle comprises fraction C of Quillaja Saponaria Molina and not fraction A of Quillaja Saponaria Molina (see claim 8).
18. The ’585 claims disclose saponin-based adjuvant is mixed in a carrier e.g. a pharmaceutically acceptable buffer. See claim 1.
The ‘585 claims do not disclose the intramuscular administration is by injection, the injection site being associated with a draining lymph node.
The ‘585 claims do not disclose the saponin-based adjuvant comprises nanoparticles of Q. saponaria saponin fraction A, cholesterol and phospholipid and nanoparticles of Q. saponaria saponin fraction C, cholesterol and phospholipid.
The ‘585 claims do not disclose the method of claim 1:
following injection of the vaccination composition at the intramuscular injection site, a fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant has a minimum value at a time greater than one hour following injection of the vaccination composition at the intramuscular injection site and less than 24 hours following injection of the vaccination composition at the intramuscular injection site, the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant at a time 24 hours following injection of the vaccination composition having a value greater than the minimum value;
the minimum value is more than about one tenth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site;
wherein the minimum value is more than about one eighth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; and
wherein the minimum value is more than about one fifth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
The ‘585 claims do not disclose the method of claim 9:
wherein, over a time period between about one hour and about twenty four hours following injection of the vaccination composition, a fraction of B cells in the dLN that are positive for i) CD45 and ii) the adjuvant has a maximum value at a time less than three hours following injection of the mixture at the intramuscular injection site;
wherein a value of the fraction of B cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one tenth of the maximum value; and
wherein a value of the fraction of cells in the downstream lymph node positive for i); CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one twentieth of the maximum value.
The ‘585 claims do not disclose the method of claim 16:
wherein, following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's blood plasma peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's blood plasma peaks at a time greater than 6 hours after the injection; and
following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's kidney peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's kidney peaks at a time greater than 24 hours after the injection.
Smith et al disclose a method for administering a vaccination composition to a mammalian subject, comprising: administering the vaccination composition at an intramuscular site of the subject; wherein the vaccination composition comprises an RSV antigen and a saponin-based adjuvant, the saponin-based adjuvant (see claim 8) comprising a saponin component (see claims) wherein the administration is by intramuscular injection. See column 32 lines 14-26.
Smith et al disclose the ISCOM (Immune Stimulating COMplex) comprises cholesterol and phospholipid. See column 29 lines 44-63.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have administered the vaccine antigens with the saponin based adjuvant or substituted the adjuvant with the saponin based adjuvant, wherein the ISCOMs comprise phospholipid and cholesterol as taught by Smith et al and administered by intramuscular injection as taught by Smith et al with the intramuscular site is a site associated with draining lymph nodes, thus resulting in the instant invention with a reasonable expectation of success. The motivation to do so is that Smith et al disclose vaccine composition comprising saponin adjuvants are administered intramuscularly by injection and Smith et al disclose that the ISCOMS comprise cholesterol and phospholipid.
Therefore, since the combination of the ‘585 claims and Smith et al disclose the same administering step as claimed, the method of the combination of the ‘585 claims and Smith et al would also result in the recited effects:
following injection of the vaccination composition at the intramuscular injection site, a fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant has a minimum value at a time greater than one hour following injection of the vaccination composition at the intramuscular injection site and less than 24 hours following injection of the vaccination composition at the intramuscular injection site, the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant at a time 24 hours following injection of the vaccination composition having a value greater than the minimum value; the minimum value is more than about one tenth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; wherein the minimum value is more than about one eighth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; wherein the minimum value is more than about one fifth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; wherein, over a time period between about one hour and about twenty four hours following injection of the vaccination composition, a fraction of B cells in the dLN that are positive for i) CD45 and ii) the adjuvant has a maximum value at a time less than three hours following injection of the mixture at the intramuscular injection site; wherein a value of the fraction of B cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one tenth of the maximum value; wherein a value of the fraction of cells in the downstream lymph node positive for i); CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one twentieth of the maximum value;
wherein, following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's blood plasma peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's blood plasma peaks at a time greater than 6 hours after the injection; following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's kidney peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's kidney peaks at a time greater than 24 hours after the injection.
Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11278612 (‘612) in view of Boddapati et al. (“Boddapati”) U.S. Patent No. 11278612 02/22/2022.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘612 claims disclose:
1: A method of providing a vaccination composition
comprising: administering the vaccination composition at an intramuscular site of the subject, the vaccination composition comprising a multivalent immunogenic influenza composition comprising (a) a detergent-core nanoparticle, wherein the detergent-core nanoparticle comprises a recombinant influenza hemagglutinin (HA) glycoprotein from a Type B influenza strain; and (b) a Hemagglutinin saponin Matrix Nanoparticle (HaSMaN), wherein the HaSMaN comprises a recombinant influenza HA glycoprotein from a Type A influenza strain and ISCOM matrix adjuvant, wherein the ISCOM matrix adjuvant consists of Fraction A Matrix and Fraction C Matrix; and (c) a pharmaceutically acceptable buffer.
The ‘612 specification teaches that Fraction A and Fraction C are fractions of Quillaja saponaria. See under matrix particles.
7. The method of claim 1, wherein the saponin-based adjuvant is mixed with influenza glycoprotein (claim 1).
8. The method of claim 1, wherein the saponin-based adjuvant is mixed with a pharmaceutically acceptable carrier.
9. The ‘612 claims disclose a method of providing a vaccination composition to a subject, comprising: administering the vaccination composition at an intramuscular site of the subject, the vaccination composition including a saponin-based adjuvant.
The ‘612 claims administering by intramuscular vaccination composition comprising a multivalent immunogenic influenza composition comprising (a) a detergent-core nanoparticle, wherein the detergent-core nanoparticle comprises a recombinant influenza hemagglutinin (HA) glycoprotein from a Type B influenza strain; and (b) a Hemagglutinin saponin Matrix Nanoparticle (HaSMaN), wherein the HaSMaN comprises a recombinant influenza HA glycoprotein from a Type A influenza strain and ISCOM matrix adjuvant, wherein the ISCOM matrix adjuvant consists of Fraction A Matrix and Fraction C Matrix; and (c) a pharmaceutically acceptable buffer.
The ‘612 specification teaches that Fraction A and Fraction C are fractions of Quillaja saponaria. See under matrix particles.
14: The ’612 claims disclose the saponin-based adjuvant is mixed with an influenza glycoprotein (claim 1).
15: The ’612 claims disclose wherein the saponin-based adjuvant is mixed with a carrier i.e. a pharmaceutically acceptable carrier. See claim 1.
16: The ’612 claims disclose a method for administering a vaccination composition to a subject, comprising: administering the vaccination composition at an intramuscular site of the subject; wherein the vaccination composition comprises an influenza antigen and a saponin-based adjuvant, the saponin-based adjuvant (see above) comprising a saponin component;
17. The ’612 claims disclose the adjuvant comprises fraction A of Quillaja Saponaria Molina and fraction C of Quillaja Saponaria Molina (see above).
18. The ’612 claims disclose saponin-based adjuvant is mixed in a carrier e.g. a pharmaceutically acceptable buffer. See claim 1.
The ‘612 claims do not disclose the intramuscular administration is by injection, the injection site being associated with a draining lymph node.
The ‘612 claims do not disclose the intramuscular administration to a mammalian subject such as a human,
The ‘612 claims do not disclose the saponin-based adjuvant comprises nanoparticles of Q. saponaria saponin fraction A, cholesterol and phospholipid and nanoparticles of Q. saponaria saponin fraction C, cholesterol and phospholipid.
The ‘612 claims do not disclose the method of claim 1:
following injection of the vaccination composition at the intramuscular injection site, a fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant has a minimum value at a time greater than one hour following injection of the vaccination composition at the intramuscular injection site and less than 24 hours following injection of the vaccination composition at the intramuscular injection site, the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant at a time 24 hours following injection of the vaccination composition having a value greater than the minimum value;
the minimum value is more than about one tenth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site;
wherein the minimum value is more than about one eighth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; and
wherein the minimum value is more than about one fifth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
The ‘612 claims do not disclose the method of claim 9:
wherein, over a time period between about one hour and about twenty four hours following injection of the vaccination composition, a fraction of B cells in the dLN that are positive for i) CD45 and ii) the adjuvant has a maximum value at a time less than three hours following injection of the mixture at the intramuscular injection site;
wherein a value of the fraction of B cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one tenth of the maximum value; and
wherein a value of the fraction of cells in the downstream lymph node positive for i); CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one twentieth of the maximum value.
The ‘612 claims do not disclose the method of claim 16:
wherein, following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's blood plasma peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's blood plasma peaks at a time greater than 6 hours after the injection; and
following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's kidney peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's kidney peaks at a time greater than 24 hours after the injection.
Boddapati et al disclose a method for administering a vaccination composition to a mammalian subject, comprising: administering the vaccination composition at an intramuscular site of the subject; wherein the vaccination composition comprises an influenza antigen and a saponin-based adjuvant, the saponin-based adjuvant comprising a saponin component wherein the administration is by intramuscular injection. See col. 7 lines 41-54 and col. 16 lines 58-66.
Boddapati et al disclose saponin adjuvant is a combination of ISCOM (Immune Stimulating COMplex) comprising the cholesterol and phospholipid and fraction A combined with ISCOM comprising the cholesterol and phospholipid and fraction C. See column 1 lines 65-67 and column 2 lines 1-39.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have administered the vaccine antigens with the saponin based adjuvant or substituted the adjuvant with the saponin based adjuvant of the ‘612 claims, wherein the saponin based adjuvant comprise ISCOMS comprising phospholipid and cholesterol and the fraction A and ISCOMS comprising phospholipid and cholesterol and the fraction C as taught by Boddapati and administered by intramuscular injection to a mammalian subject such as a human as taught by Boddapati, the intramuscular site is a site associated with draining lymph nodes, thus resulting in the instant invention with a reasonable expectation of success.
The motivation to do so is that Boddapati disclose vaccine composition comprising the ISCOMs comprise cholesterol and lipid and are administered intramuscularly by injection to a mammalian subject such as a human.
Therefore, since the combination of the ‘612 claims and Boddapati disclose the same administering step as claimed, the method of the combination of the ‘612 claims and Boddapati would also result in the recited effects:
following injection of the vaccination composition at the intramuscular injection site, a fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant has a minimum value at a time greater than one hour following injection of the vaccination composition at the intramuscular injection site and less than 24 hours following injection of the vaccination composition at the intramuscular injection site, the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant at a time 24 hours following injection of the vaccination composition having a value greater than the minimum value; the minimum value is more than about one tenth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; wherein the minimum value is more than about one eighth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; wherein the minimum value is more than about one fifth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; wherein, over a time period between about one hour and about twenty four hours following injection of the vaccination composition, a fraction of B cells in the dLN that are positive for i) CD45 and ii) the adjuvant has a maximum value at a time less than three hours following injection of the mixture at the intramuscular injection site; wherein a value of the fraction of B cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one tenth of the maximum value; wherein a value of the fraction of cells in the downstream lymph node positive for i); CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one twentieth of the maximum value;
wherein, following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's blood plasma peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's blood plasma peaks at a time greater than 6 hours after the injection; following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's kidney peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's kidney peaks at a time greater than 24 hours after the injection.
Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11896662(‘662) in view of Boddapati et al. (“Boddapati”) U.S. Patent No. 11278612 02/22/2022 cited in IDS.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘662 claims disclose:
1: A method of providing a vaccination composition
comprising: administering the vaccination composition at an intramuscular site of the subject, the vaccination composition comprising a multivalent immunogenic influenza composition comprising (a) a detergent-core nanoparticle, wherein the detergent-core nanoparticle comprises a recombinant influenza hemagglutinin (HA) glycoprotein from a Type B influenza strain; and (b) a Hemagglutinin saponin Matrix Nanoparticle (HaSMaN), wherein the HaSMaN comprises a recombinant influenza HA glycoprotein from a Type A influenza strain and ISCOM matrix adjuvant, wherein the ISCOM matrix adjuvant consists of Fraction A Matrix and Fraction C Matrix; and (c) a pharmaceutically acceptable buffer.
The ‘662 specification teaches that Fraction A and Fraction C are fractions of Quillaja saponaria. See under matrix particles.
7. The method of claim 1, wherein the saponin-based adjuvant is mixed with influenza glycoprotein (claim 1).
8. The method of claim 1, wherein the saponin-based adjuvant is mixed with a pharmaceutically acceptable carrier.
9. The ‘662 claims disclose a method of providing a vaccination composition to a subject, comprising: administering the vaccination composition at an intramuscular site of the subject, the vaccination composition including a saponin-based adjuvant.
The ‘662 claims administering by intramuscular vaccination composition comprising a multivalent immunogenic influenza composition comprising (a) a detergent-core nanoparticle, wherein the detergent-core nanoparticle comprises a recombinant influenza hemagglutinin (HA) glycoprotein from a Type B influenza strain; and (b) a Hemagglutinin saponin Matrix Nanoparticle (HaSMaN), wherein the HaSMaN comprises a recombinant influenza HA glycoprotein from a Type A influenza strain and ISCOM matrix adjuvant, wherein the ISCOM matrix adjuvant consists of Fraction A Matrix and Fraction C Matrix; and (c) a pharmaceutically acceptable buffer.
The ‘‘662 specification teaches that Fraction A and Fraction C are fractions of Quillaja saponaria. See under matrix particles.
14: The ‘662claims disclose the saponin-based adjuvant is mixed with an influenza glycoprotein (claim 1).
15: The‘662claims disclose wherein the saponin-based adjuvant is mixed with a carrier i.e. a pharmaceutically acceptable carrier. See claim 1.
16: The ‘662 claims disclose a method for administering a vaccination composition to a subject, comprising: administering the vaccination composition at an intramuscular site of the subject; wherein the vaccination composition comprises an influenza antigen and a saponin-based adjuvant, the saponin-based adjuvant (see above) comprising a saponin component.
17. The‘662 claims disclose the adjuvant comprises fraction A of Quillaja Saponaria Molina and fraction C of Quillaja Saponaria Molina (see above).
18. The ‘662 claims disclose saponin-based adjuvant is mixed in a carrier e.g. a pharmaceutically acceptable buffer. See claim 1.
The ‘662 claims do not disclose the intramuscular administration is by injection, the injection site being associated with a draining lymph node.
The ‘662 claims do not disclose the intramuscular administration to a mammalian subject such as a human,
The ‘662 claims do not disclose the saponin-based adjuvant comprises nanoparticles of Q. saponaria saponin fraction A, cholesterol and phospholipid and nanoparticles of Q. saponaria saponin fraction C, cholesterol and phospholipid.
The ‘662 claims do not disclose the method of claim 1:
following injection of the vaccination composition at the intramuscular injection site, a fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant has a minimum value at a time greater than one hour following injection of the vaccination composition at the intramuscular injection site and less than 24 hours following injection of the vaccination composition at the intramuscular injection site, the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant at a time 24 hours following injection of the vaccination composition having a value greater than the minimum value;
the minimum value is more than about one tenth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site;
wherein the minimum value is more than about one eighth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; and
wherein the minimum value is more than about one fifth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site.
The ‘662 claims do not disclose the method of claim 9:
wherein, over a time period between about one hour and about twenty four hours following injection of the vaccination composition, a fraction of B cells in the dLN that are positive for i) CD45 and ii) the adjuvant has a maximum value at a time less than three hours following injection of the mixture at the intramuscular injection site;
wherein a value of the fraction of B cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one tenth of the maximum value; and
wherein a value of the fraction of cells in the downstream lymph node positive for i); CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one twentieth of the maximum value.
The ‘662 claims do not disclose the method of claim 16:
wherein, following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's blood plasma peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's blood plasma peaks at a time greater than 6 hours after the injection; and
following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's kidney peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's kidney peaks at a time greater than 24 hours after the injection.
Boddapati et al disclose a method for administering a vaccination composition to a mammalian subject, comprising: administering the vaccination composition at an intramuscular site of the subject; wherein the vaccination composition comprises an influenza antigen and a saponin-based adjuvant, the saponin-based adjuvant comprising a saponin component wherein the administration is by intramuscular injection. See col. 7 lines 41-54 and col. 16 lines 58-66.
Boddapati et al disclose saponin adjuvant is a combination of ISCOM (Immune Stimulating COMplex) comprising the cholesterol and phospholipid and fraction A combined with ISCOM comprising the cholesterol and phospholipid and fraction C. See column 1 lines 65-67 and column 2 lines 1-39.
It would have been prima facie obvious to a person of ordinary skill in the art as of the effective filing date of the instant invention to have administered the vaccine antigens with the saponin based adjuvant or substituted the adjuvant with the saponin based adjuvant of the ‘662 claims, wherein the saponin based adjuvant comprise ISCOMS comprising phospholipid and cholesterol and the fraction A and ISCOMS comprising phospholipid and cholesterol and the fraction C as taught by Boddapati and administered by intramuscular injection to a mammalian subject such as a human as taught by Boddapati, the intramuscular site is a site associated with draining lymph nodes, thus resulting in the instant invention with a reasonable expectation of success.
The motivation to do so is that Boddapati disclose vaccine composition comprising the ISCOMs comprise cholesterol and lipid and are administered intramuscularly by injection to a mammalian subject such as a human.
Therefore, since the combination of the ‘662 claims and Boddapati disclose the same administering step as claimed, the method of the combination of the ‘662 claims and Boddapati would also result in the recited effects:
following injection of the vaccination composition at the intramuscular injection site, a fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant has a minimum value at a time greater than one hour following injection of the vaccination composition at the intramuscular injection site and less than 24 hours following injection of the vaccination composition at the intramuscular injection site, the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant at a time 24 hours following injection of the vaccination composition having a value greater than the minimum value; the minimum value is more than about one tenth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; wherein the minimum value is more than about one eighth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; wherein the minimum value is more than about one fifth of a maximum value of the fraction of T cells in the dLN that are positive for i) CD45 and ii) the saponin-based adjuvant between one hour and twenty four hours following injection of the vaccination composition at the intramuscular injection site; wherein, over a time period between about one hour and about twenty four hours following injection of the vaccination composition, a fraction of B cells in the dLN that are positive for i) CD45 and ii) the adjuvant has a maximum value at a time less than three hours following injection of the mixture at the intramuscular injection site; wherein a value of the fraction of B cells in the downstream lymph node positive for i) CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one tenth of the maximum value; wherein a value of the fraction of cells in the downstream lymph node positive for i); CD45 and ii) the adjuvant that are B cells at about twenty four hours following injection of the mixture at the intramuscular injection site is less than about one twentieth of the maximum value;
wherein, following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's blood plasma peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's blood plasma peaks at a time greater than 6 hours after the injection; following injection of the vaccination composition at the intramuscular injection site of the subject, concentration of the saponin component in the subject's kidney peaks at a time less than 3 hours after the injection, and concentration of the cholesterol component in the subject's kidney peaks at a time greater than 24 hours after the injection.
Citation of Relevant Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Hill et al (WO 2019021013) disclose Matrix-M™ is suitable for human use and consists of saponin-based 40 nm particles that can activate and recruit immune cells to the draining lymph nodes and spleen. See page 33 lines 22-24.
Status of Claims
Claims 1-19 are rejected.
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/OLUWATOSIN A OGUNBIYI/ Primary Examiner, Art Unit 1645
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