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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 13, 2026 has been entered.
Claims 1, 4-13, 31, 35, and 42-46 are currently pending. Claims 1, 11 and 42 have been amended. Claims 43-46 have been added. Claims 31 and 35 were previously withdrawn. Claims 1, 4-13, and 42-46 are currently under examination.
Objections Withdrawn
2. In view of Applicant’s amendment the objection to claim 42 for incorrectly spelling ‘Cetylpyridinium’ is withdrawn.
Rejections Withdrawn
3. In view of Applicant’s amendment, the rejection of claims 1 and 42 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 by the use of the phrase “at least one isolated mycobacterial antigen, or an antigenic fragment thereof selected from the group consisting of” is withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
4. The rejection of claims 1, 4-9, 12, 13, and 42 under 35 U.S.C. 103 as being unpatentable over Edelson et al., US 2012/0328701 A1; Published: 12/27/12, and further in view of Aagaard et al., A multistage tuberculosis vaccine that confers efficient protection before and after exposure, Nature Medicine, 2011; pages 1-7 is maintained for the reasons set forth in the previous office action.
Independent claim 1 is drawn to a composition comprising: a formulation for intranasal administration comprising: (a) a nanoemulsion comprising: (i) an aqueous phase; (ii) about 1% to about 80% (v/v) of at least one oil; (iii) about 0.001% to about 10% (v/v) of at least one surfactant; (iv) about 0.01% to about 50% (v/v) of at least one solvent; (v) less than about 5% (v/v) of at least one quaternary ammonium compound; and b) isolated mycobacterial antigen comprising (i) ESAT-6, (ii) Ag85B; (iii) MTB32A and MTB29A; (iv) Ag85B and ESAT6; or (v) Ag85B, ESAT-6, rpfD, Rv1733c, and Rv2626c; wherein the nanoemulsion consists of droplets with an average diameter of less than about 1,000 nm.
Independent claim 42 is drawn to a composition comprising: a formulation for intranasal administration comprising: (a) a nanoemulsion, or a dilution thereof, wherein the nanoemulsion comprises: (i) an aqueous phase; (ii) about 1% to about 80% (v/v) of Soybean oil; (iii) about 0.001% to about 10% (v/v) of Polysorbate 80; (iv) about 0.01% to about 50% (v/v) of alcohol; and (v) less than about 5% (v/v) of Cetylpyridinium chloride; and b) isolated mycobacterial antigen comprising (i) ESAT-6; (ii) Ag85B; (iii) MTB32A and MTB39A; (iv) Ag85B and ESAT-6; or (v) Ag85B, ESAT-6, rpfD, Rv1733c, and Rv2626c; wherein the nanoemulsion consists of droplets with an average diameter of less than about 1,000 nm.
Edelson et al. teach nanoparticle composition formulations comprising a nanoemulsion. Said nanoemulsion comprises polysorbate 80 from about 1 to about 10% (meets claim 1(iii), 6, & 42(iii); paragraph 0120), propylparaben, isotonic sodium chloride solution, methylparaben, a buffer solution (comprising gelatin, sodium phosphate dibasic, purified water (meets claim 1(iv)), and hydrochloric acid) and, optionally, a known therapeutic agent and/or independently active biologically active agent may include antigens of Mycobacterium tuberculosis (see paragraph 0340; partially meeting claim 1(b) and claim 42(b)). Further, Edelson et al. teach suitable surfactants (at 0-10%; paragraph 0120; meets claim 1(iii)&42(iii)) or emulsifying agents including polysorbate 20, alcohol and benzalkonium chloride (see paragraph 0093; meets claim 1(v), 6, 7, & 42 (iv)).
Edelson teaches that the nanoemulsion comprises oil and surfactant (meets claim 1(iii) see paragraph 0009). An oily dispersion medium comprises, consists essentially of, or consists of soybean oil (meets claim 42), canola oil, safflower oil, olive oil, corn oil, palm oil, peanut oil, sunflower oil, rapeseed oil, cocoa butter, almond oil, cashew oil, hazelnut oil, avocado oil, and/or combinations thereof (see paragraph 0087; meeting claim 5). The percent of oil in the premix ranges between 0% and 50% (see paragraph 0087&0115; meeting claim 1(ii)&42(ii)). Moreover, the term "nanoemulsion," as used herein, refers to an emulsion in which at least some of the droplets (or particles) have diameters in the nanometer size range. As will be understood by those of ordinary skill in the art, a nanoemulsion is characterized by droplets or particles one thousand fold smaller than microemulsion droplets or particles (see paragraph 0052; meeting claim 1(b)&42(b)).
In some embodiments, compositions utilizing such ratios of aqueous dispersion medium (e.g., water, buffer, salt solution, etc.) to surfactant comprise water-in-oil emulsions (see paragraph 0112; meeting claim 1(i)&42(i)). Such suitable surfactants or emulsifying agents also include a quaternary ammonium ion (e.g., cetylpyridinium chloride [CPC]; meeting claim 1(v), 8, 42(v)). Edelson also teaches that water can be used for injection, the composition may comprise the use of phosphate buffered saline, purified water, and deionized water (see paragraphs 0189-190 and 589; meeting claim 4). Lastly, Edelson teaches that particles within the nanoparticle compositions have diameters (e.g., average and/or median diameters) that are smaller than about 1000 nm (see paragraph 0145; meeting claim 1(b)&42(b)).
Edelson et al. do not specifically teach that their antigen is an isolated mycobacterial antigen comprising (i) ESAT-6, (ii) Ag85B; (iii) MTB32A and MTB29A; (iv) Ag85B and ESAT6; or (v) Ag85B, ESAT-6, rpfD, Rv1733c, and Rv2626c, as recited in claim 1 & 42; or that said antigen is present in an amount of from about 10 µg to about 50 µg, as recited in claim 9.
Aagaard et al. teach that all tuberculosis vaccines currently in clinical trials are designed as prophylactic vaccines based on early expressed antigens. They developed a multistage vaccination strategy in which the early antigens Ag85B and 6-kDa early secretory antigenic target (ESAT-6) are combined with the latency-associated protein Rv2660c (H56 vaccine) (meeting 1(b)(iv) and 42(b)(iv). The study reported on the design, construction and evaluation before and after Mtb exposure of a new multistage vaccine, H56 that combines Ag85B, ESAT-6 and Rv2660c. Moreover, Aagaard et al. teach that to construct the H56 vaccine, they purified the recombinant H56 fusion protein (Ag85B-ESAT6-Rv2660c) and formulated it with a cationic adjuvant (CAF01)14. Mice were vaccinated three times with doses from 0.01 to 10 µg (meeting the limitation of claim 9). Vaccinated mice were protected at all H56 doses, but the best protection occurred with a 5-µg dose (see page 2; Initial evaluation of H56 and its protein components).
It would have been obvious before the effective filing date of the presently claimed invention to employ at least one antigen or specific combination of antigen specifically Ag85B and ESAT-6 with a reasonable expectation of success. The skilled artisan would have expected success in substituting Aagaard’s tuberculosis related antigens for those exemplified in Edelson’s pharmaceutical formulation because Aagaard teaches that Ag85B and ESAT-6 promote a stronger response against multiple components and have the ability to induce moderate protection while controlling bacteria growth. Thus, the person of ordinary skill in the art would have found it obvious to make the substitution because ordinary skilled artisans would have predicted that those M. tuberculosis antigens would be effective as a part of the nanoemulsion as claimed.
Further, the claim would have been obvious because the substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. See the recent Board decision Ex parte Smith,--USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396).
As it pertains to claim 9, the claimed method requires an antigen in an amount from about 10 µg to about 50 µg, which overlaps with the range of Aagaard because Aagaard teaches doses from 0.01 to 10 µg. Because the claimed range overlaps with the range disclose by the prior art, a prima facie case of obviousness exists.
Accordingly, the subject matter of the rejected claims would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Applicant argues that:
1) Neither Edelson nor Annis discloses a Mtb antigen selected from ESAT-6; Ag85B; MTB32A and MTB29A; Ag85B and ESAT6; or Ag85B, ESAT-6, rpfD, Rv1733c, and Rv2626c in combination with the adjuvant for use in intranasal administration. Without any motivation or suggestion, one of ordinary skill in the art could not have reasonably predicted that the composition would work.
2) Aagaard discloses a vaccine formulated with a combination of antigens Ag85B, ESAT-6, and Rv2660c with CAF01, an adjuvant for parenteral administration as a booster for BCG. However, the same combination of antigen and adjuvant when administered mucosally as a booster did not provide any improvement.
Applicant’s arguments have been fully considered, but are deemed non-persuasive.
With regard to Point 1, The Office takes the position that the claims are drawn to a composition having components (a) and (b). The combination of references teaches those components for the same use. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850,205 USPQ 1069, 1072 (CCPA 1980).
Additionally, the Office takes the position that the prior art meet the prior art. The claims require ESAT-6; Ag85B; or Ag85B and ESAT6. The primary reference encompasses the nanoemulsion composition as claimed comprising Mycobacterium tuberculosis antigens. It also teaches the route of administration to include intranasal (see paragraph 0511). Additionally, the amendment to section (b) has removed "at least one", but written in the alternative still reads on all or just one. Further, the secondary reference teaches Ag85B, which reads on 1 (b)(ii)).
With regard to Point 2, CAF01 is a liposome based adjuvant that significantly enhances immune response when used for nasal administration. Moreover, Aagaard discusses aerosol administration and notes that after determining the optimal dose, they compared immune responses and protection by H56 and its individual components. In all groups, they found vaccine-specific responses, but the immunogenicity of the single proteins varied considerably, with Ag85B being the most immunogenic and Rv2660c being the least (Fig. 1c). H56 vaccination promoted a stronger response against all three components than vaccines based on the individual antigens. Six weeks after vaccination, they challenged the mice and determined the bacterial loads in their lungs 6 weeks later (Fig. 1d). Both Ag85B and ESAT-6 vaccination induced moderate protection, but only Ag85B was statistically different from the control.
5. The rejection of claims 1, 5-, 10, 12 and 42 under 35 U.S.C. 103 as being unpatentable over Annis et al., US 2006/0251684 A1; Published: 11/9/06, and further in view of Aagaard et al., A multistage tuberculosis vaccine that confers efficient protection before and after exposure, Nature Medicine, 2011; pages 1-7 is maintained for the reasons set forth in the previous office action.
Independent claim 1 is drawn to a composition comprising: a formulation for intranasal administration comprising: (a) a nanoemulsion comprising: (i) an aqueous phase; (ii) about 1% to about 80% (v/v) of at least one oil; (iii) about 0.001% to about 10% (v/v) of at least one surfactant; (iv) about 0.01% to about 50% (v/v) of at least one solvent; (v) less than about 5% (v/v) of at least one quaternary ammonium compound; and b) isolated mycobacterial antigen comprising (i) ESAT-6, (ii) Ag85B; (iii) MTB32A and MTB29A; (iv) Ag85B and ESAT6; or (v) Ag85B, ESAT-6, rpfD, Rv1733c, and Rv2626c; wherein the nanoemulsion consists of droplets with an average diameter of less than about 1,000 nm.
Independent claim 42 is drawn to a composition comprising: a formulation for intranasal administration comprising: (a) a nanoemulsion, or a dilution thereof, wherein the nanoemulsion comprises: (i) an aqueous phase; (ii) about 1% to about 80% (v/v) of Soybean oil; (iii) about 0.001% to about 10% (v/v) of Polysorbate 80; (iv) about 0.01% to about 50% (v/v) of alcohol; and (v) less than about 5% (v/v) of Cetylpyridinium chloride; and b) isolated mycobacterial antigen comprising (i) ESAT-6; (ii) Ag85B; (iii) MTB32A and MTB39A; (iv) Ag85B and ESAT-6; or (v) Ag85B, ESAT-6, rpfD, Rv1733c, and Rv2626c; wherein the nanoemulsion consists of droplets with an average diameter of less than about 1,000 nm.
Annis et al. provides emulsions comprising an aqueous phase, an oil phase comprising an oil and an organic solvent, and at least one surfactant. The emulsion comprises particles having an average diameter of less than 150 nm (see paragraph 0009; meeting claims 1((i), (iii), (iv), (b) & 42((i), (iii), (iv), (b)). The oil phase of a nanoemulsion contains an oil and an organic solvent. The oil phase of a nanoemulsion contains about 30 to about 90 vol % oil, based on the total volume of the nanoemulsion. The oil phase also contains from about 3 to about 15 vol % and about 5 to about 10 vol % of an organic solvent based on the total volume of the nanoemulsion (see paragraph 0030; meeting claims 1 (ii) and (iv) & 42 (ii) and (iv)). Further, the nanoemulsion composition contains substantially inactivated Mycobacteria tuberculosis or a portion thereof (see paragraph 0089; meeting claim 1(b), 2 and 42(b)). The antigen is ranged from between about 2.3 .mu.g to about 30 .mu.g (see paragraph 0087; meeting claim 10).
Suitable oils include, but are not limited to, soybean oil (meets claim 5 & 42(ii)), avocado oil, squalene oil, olive oil, canola oil, corn oil, rapeseed oil, safflower oil, sunflower oil, fish oils, coconut oil, cottonseed oil, flaxseed oil, mineral oil, water insoluble vitamins, and combinations comprising one or more of the foregoing oils (see paragraph 0031). Suitable organic solvents include organic phosphate solvents, alcohols, and combinations comprising one or more of the foregoing solvents (see paragraph 0032-33; meets claim 7 & 42(iv)).
Small particle size nanoemulsion compositions can also contain one or more surfactants, present in the aqueous phase (meets claim 1(i)&42(i), the oil phase, or both phases of a nanoemulsion. The nanoemulsion contains about 3 to about 15 vol % or about 5 to about 10 vol % of surfactant (see paragraph 0034; meeting claim 1 (iii)& 42(iii)) and include the polysorbate detergents sold under the tradenames TWEEN.RTM. 20, and TWEEN.RTM. 80 (see paragraph 0035; meeting claim 6 & 42(iii)). Moreover, Annis et al. teach that the nanoemulsion comprises suitable cationic halogen-containing compounds including cetylpyridinium chloride (see paragraph 0041; meeting claim 1(v), 8 and 42(v)).
Annis notes that an emulsion is a composition containing an aqueous phase and an oil phase. The term "emulsion" refers to, without limitation, any oil-in-water dispersions or droplets. Classical or standard emulsions comprise lipid structures having an average particle size of greater than about 5 .mu.m in diameter. Standard nanomulsions having smaller particle sizes are known, and comprise lipid structures having an average particle diameter of about 500 nm to about 5 .mu.m (see paragraph 0027; meeting claim 12). The concentration of antigen can range from approximately 1 .mu.g to approximately 1 mg (see paragraph 0085; meeting claim 9).
Annis does not specifically teach that their antigen are isolated mycobacterial antigen comprising (i) ESAT-6, (ii) Ag85B; (iii) MTB32A and MTB29A; (iv) Ag85B and ESAT6; or (v) Ag85B, ESAT-6, rpfD, Rv1733c, and Rv2626c, as recited in claim 1 and 42.
Aagaard et al. teach that all tuberculosis vaccines currently in clinical trials are designed as prophylactic vaccines based on early expressed antigens. They developed a multistage vaccination strategy in which the early antigens Ag85B and 6-kDa early secretory antigenic target (ESAT-6) are combined with the latency-associated protein Rv2660c (H56 vaccine). The study reported on the design, construction and evaluation before and after Mtb exposure of a new multistage vaccine, H56 that combines Ag85B, ESAT-6 and Rv2660c. Moreover, Aagaard et al. teach that to construct the H56 vaccine, they purified the recombinant H56 fusion protein (Ag85B-ESAT6-Rv2660c) and formulated it with a cationic adjuvant (CAF01)14. Mice were vaccinated three times with doses from 0.01 to 10 µg (meeting the limitation of claim 9). Vaccinated mice were protected at all H56 doses, but the best protection occurred with a 5-µg dose (see page 2; Initial evaluation of H56 and its protein components).
It would have been obvious before the effective filing date of the presently claimed invention to employ at least one antigen or specific combination of antigen specifically Ag85B and ESAT-6 with a reasonable expectation of success. The skilled artisan would have expected success in substituting Aagaard’s tuberculosis related antigens for those exemplified in Annis’ pharmaceutical formulation because Aagaard teaches that Ag85B and ESAT-6 promote a stronger response against multiple components and have the ability to induce moderate protection while controlling bacteria growth. Thus, the person of ordinary skill in the art would have found it obvious to make the substitution because ordinary skilled artisans would have predicted that those M. tuberculosis antigens would be effective as a part of the nanoemulsion as claimed.
Further, the claim would have been obvious because the substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. See the recent Board decision Ex parte Smith,--USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396).
Applicant argues that:
1) Neither Edelson nor Annis discloses a Mtb antigen selected from ESAT-6; Ag85B; MTB32A and MTB29A; Ag85B and ESAT6; or Ag85B, ESAT-6, rpfD, Rv1733c, and Rv2626c in combination with the adjuvant for use in intranasal administration. Without any motivation or suggestion, one of ordinary skill in the art could not have reasonably predicted that the composition would work.
2) Aagaard discloses a vaccine formulated with a combination of antigens Ag85B, ESAT-6, and Rv2660c with CAF01, an adjuvant for parenteral administration as a booster for BCG. However, the same combination of antigen and adjuvant when administered mucosally as a booster did not provide any improvement.
Applicant’s arguments have been fully considered, but are deemed non-persuasive.
With regard to Point 1, The Office takes the position that the claims are drawn to a composition having components (a) and (b). The combination of references teaches those components for the same use. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850,205 USPQ 1069, 1072 (CCPA 1980).
Additionally, the Office takes the position that the prior art meet the prior art. The claims require ESAT-6; Ag85B; or Ag85B and ESAT6. The primary reference encompasses the nanoemulsion composition as claimed comprising Mycobacterium tuberculosis antigens. It also teaches the route of administration to include intranasal (see paragraph 0511). Additionally, the amendment to section (b) has removed "at least one", but written in the alternative still reads on all or just one. Further, the secondary reference teaches Ag85B, which reads on 1 (b)(ii)).
With regard to Point 2, CAF01 is a liposome based adjuvant that significantly enhances immune response when used for nasal administration. Moreover, Aagaard discusses aerosol administration and notes that after determining the optimal dose, they compared immune responses and protection by H56 and its individual components. In all groups, they found vaccine-specific responses, but the immunogenicity of the single proteins varied considerably, with Ag85B being the most immunogenic and Rv2660c being the least (Fig. 1c). H56 vaccination promoted a stronger response against all three components than vaccines based on the individual antigens. Six weeks after vaccination, they challenged the mice and determined the bacterial loads in their lungs 6 weeks later (Fig. 1d). Both Ag85B and ESAT-6 vaccination induced moderate protection, but only Ag85B was statistically different from the control.
New Grounds Of Objection and Rejection
Claim Objections
6. Claims 43-44 and 46 are objected to because of the following informalities: Said claims are objected to for depending upon a rejected based claimed. Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
7. Claims 1, 4-13, 42 and 45 under 35 U.S.C. 103 as being unpatentable over Edelson et al., US 2012/0328701 A1; Published: 12/27/12, and further in view of Anantha et al., US 2014/0377300 A1; Published: 12/25/14
Independent claim 1 is drawn to a composition comprising: a formulation for intranasal administration comprising: (a) a nanoemulsion comprising: (i) an aqueous phase; (ii) about 1% to about 80% (v/v) of at least one oil; (iii) about 0.001% to about 10% (v/v) of at least one surfactant; (iv) about 0.01% to about 50% (v/v) of at least one solvent; (v) less than about 5% (v/v) of at least one quaternary ammonium compound; and b) isolated mycobacterial antigen comprising (i) ESAT-6, (ii) Ag85B; (iii) MTB32A and MTB29A; (iv) Ag85B and ESAT6; or (v) Ag85B, ESAT-6, rpfD, Rv1733c, and Rv2626c; wherein the nanoemulsion consists of droplets with an average diameter of less than about 1,000 nm.
Independent claim 42 is drawn to a composition comprising: a formulation for intranasal administration comprising: (a) a nanoemulsion, or a dilution thereof, wherein the nanoemulsion comprises: (i) an aqueous phase; (ii) about 1% to about 80% (v/v) of Soybean oil; (iii) about 0.001% to about 10% (v/v) of Polysorbate 80; (iv) about 0.01% to about 50% (v/v) of alcohol; and (v) less than about 5% (v/v) of Cetylpyridinium chloride; and b) isolated mycobacterial antigen comprising (i) ESAT-6; (ii) Ag85B; (iii) MTB32A and MTB39A; (iv) Ag85B and ESAT-6; or (v) Ag85B, ESAT-6, rpfD, Rv1733c, and Rv2626c; wherein the nanoemulsion consists of droplets with an average diameter of less than about 1,000 nm.
Edelson et al. teach nanoparticle composition formulations comprising a nanoemulsion. Said nanoemulsion comprises polysorbate 80 from about 1 to about 10% (meets claim 1(iii), 6, & 42(iii); paragraph 0120), propylparaben, isotonic sodium chloride solution, methylparaben, a buffer solution (comprising gelatin, sodium phosphate dibasic, purified water (meets claim 1(iv)), and hydrochloric acid) and, optionally, a known therapeutic agent and/or independently active biologically active agent may include antigens of Mycobacterium tuberculosis (see paragraph 0340; partially meeting claim 1(b) and claim 42(b)). Further, Edelson et al. teach suitable surfactants (at 0-10%; paragraph 0120; meets claim 1(iii)&42(iii)) or emulsifying agents including polysorbate 20, alcohol and benzalkonium chloride (see paragraph 0093; meets claim 1(v), 6, 7, & 42 (iv)).
Edelson teaches that the nanoemulsion comprises oil and surfactant (meets claim 1(iii) see paragraph 0009). An oily dispersion medium comprises, consists essentially of, or consists of soybean oil (meets claim 42), canola oil, safflower oil, olive oil, corn oil, palm oil, peanut oil, sunflower oil, rapeseed oil, cocoa butter, almond oil, cashew oil, hazelnut oil, avocado oil, and/or combinations thereof (see paragraph 0087; meeting claim 5). The percent of oil in the premix ranges between 0% and 50% (see paragraph 0087&0115; meeting claim 1(ii)&42(ii)). Moreover, the term "nanoemulsion," as used herein, refers to an emulsion in which at least some of the droplets (or particles) have diameters in the nanometer size range. As will be understood by those of ordinary skill in the art, a nanoemulsion is characterized by droplets or particles one thousand fold smaller than microemulsion droplets or particles (see paragraph 0052; meeting claim 1(b)&42(b)).
In some embodiments, compositions utilizing such ratios of aqueous dispersion medium (e.g., water, buffer, salt solution, etc.) to surfactant comprise water-in-oil emulsions (see paragraph 0112; meeting claim 1(i)&42(i)). Such suitable surfactants or emulsifying agents also include a quaternary ammonium ion (e.g., cetylpyridinium chloride [CPC]; meeting claim 1(v), 8, 42(v)). Edelson also teaches that water can be used for injection, the composition may comprise the use of phosphate buffered saline, purified water, and deionized water (see paragraphs 0189-190 and 589; meeting claim 4). Lastly, Edelson teaches that particles within the nanoparticle compositions have diameters (e.g., average and/or median diameters) that are smaller than about 1000 nm (see paragraph 0145; meeting claim 1(b)&42(b)).
Edelson et al. do not specifically teach that their antigens are Ag85B, ESAT-6, rpfD, Rv1733c, and Rv2626c, as recited in claim 1 & 42; that said antigen is present in an amount of from about 10 µg to about 50 µg, as recited in claim 9; or that the composition further comprises at least one isolated mycobacterial antigen selected from CFP10, Hsp16.3, Ag85A, Ag85C, Rv3407, Rv2626, Rpfb, Rpfd, and RpfE, as recited in claim 11.
Anantha et al. teach fusion proteins comprising Mycobacterium tuberculosis antigens. Specifically, the fusion protein comprises Ag85B-ESAT6-Rv1733c-Rv2626c-RpfD (see paragraph 0087; meeting claim 1(b)(v) and 42(b)(v)). Said antigen is up to and including 1, 5, 10, 25 and 50 micrograms (see paragraph 0138; meets claims 9-10). As used herein, “Mtb antigen” means an antigen from Mycobacterium tuberculosis, which may be an isolated antigen, or an antigen that forms part of a fusion protein with other antigen(s) (see paragraph 0050; meets limitations of claims 1, 9-11, and 42). In some embodiments, the Mtb antigen is RpfB, RpfD, or RpfE (see paragraph 0122&0125; meets claim 11).
The present disclosure also provides compositions comprising any one or more of the fusion proteins, Mtb antigens, nucleic acid molecules encoding Mtb antigens, including fusion proteins thereof, cells, and/or vectors and a pharmaceutically acceptable carrier. Carriers include, but are not limited to, phosphate buffered saline, physiological saline, water, citrate/sucrose/Tween formulations and emulsions such as, for example, oil/water emulsions (see paragraph 0127). Further, Liquid formulations of pharmaceutical compositions can also include solutions, emulsions, syrups and elixirs containing, together with the active compound(s), wetting agents, sweeteners, and coloring and flavoring agents. Various liquid and powder formulations of the pharmaceutical compositions can be prepared by conventional methods for inhalation into the lungs of the mammal to be treated (see paragraph 0131; meeting claims 1 and 42). The compositions can further comprise an adjuvants (see paragraph 0141).
Effective doses of the compositions of the present disclosure, for the treatment of a condition vary depending upon many different factors, including means of administration, target site, physiological state of the subject, whether the subject is human or an animal, other medications administered, and whether treatment is prophylactic or therapeutic. Usually, the subject is a human but non-human mammals including transgenic mammals can also be treated (see paragraph 0135; meets claim 45). Alternately, the compositions can be administered to a subject by routes including oral, nasal, ophthalmic, rectal, or topical. The most typical route of administration is intravascular, subcutaneous, or intramuscular, although other routes can be effective (see paragraph 0136). In other embodiments, a subject who is not presently receiving treatment but has undergone a previous course of treatment is monitored for antibody levels or profiles to determine whether a resumption of treatment is required (see paragraph 0154; meets claim 45).
It would have been obvious before the effective filing date of the presently claimed invention to employ the combination of antigens, specifically, Ag85B-ESAT6-Rv1733c-Rv2626c-RpfD with a reasonable expectation of success. The skilled artisan would have expected success in substituting Anantha tuberculosis related antigens for those exemplified in Edelson’s pharmaceutical formulation because Anantha teaches that their combination of antigens create tuberculosis vaccines comprising specified Mycobacterium tuberculosis (Mtb) antigens which are involved with 3 identified stages of disease: 1) infection or acute infection, 2) latency or the latent state, and 3) resuscitation or reactivation of active disease thereby providing a strategic combination of antigens which are incorporated into a variety of delivery platforms in such a way as to provide pathways to a matrix of matched combinations of antigen delivery to obtain an optimized immune response.
Thus, the person of ordinary skill in the art would have found it obvious to make the substitution because ordinary skilled artisans would have predicted that those M. tuberculosis antigens would be effective as a part of the nanoemulsion as claimed. Further, the claim would have been obvious because the substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. See the recent Board decision Ex parte Smith,--USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396).
Accordingly, the subject matter of the rejected claims would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Conclusion
8. No claim is allowed.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAKIA J JACKSON-TONGUE whose telephone number is (571)272-2921. The examiner can normally be reached Monday-Friday 930AM-530PM.
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/LAKIA J JACKSON-TONGUE/Examiner, Art Unit 1645 February 7, 2026
/BRIAN GANGLE/Primary Examiner, Art Unit 1645