DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Remark
Applicant’s response and claims amendment were filed on 09/29/2025. Claims 1, 3, 5, 8, 14, 16, 17, 18, 20 and 23 were amended and entered. Claims 22 and 24-25 were canceled.
The status of claims
Claims 7, 15, 22 and 24-25 have been canceled.
Claims 1-6 and 8-14 with elected species of influenza virus antigen with sodium citrate as an excipient are considered.
Claims 1, 3, 5, 8, 14, 16, 17, 18, 20 and 23 have been withdrawn from consideration.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 4 is still rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph 112 (b).
Applicant traverses the rejection and submitted that term is used for meaning of the distribution of particle sizes within a sample.
Applicants’ argument has been respectfully considered; however, it is not found persuasive because the defintion of the particle and size of particle are still not explained. The description of the size of the particle is 40-90% are still hard to be understood.
In the previous office action, Applicants are referred to the MPEP 2173.05(a), which cites:” Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999).
The specification are carefully reviewed, the defintion of the particle and size of the particle are not defined and explained.in the section of the section of defintion in the specification.
The definition of Particle given by Merian Weber Dictionary is defined as a minute quantity or fragment or a relatively small or the smallest discrete portion or amount of something. In chemistry, a particle is defined by Chemistry Dictionary as a general term for any microscopic components of matter, which can include atoms, molecules, ions, and subatomic particles like protons, neutrons, and electrons. Moreover, the size of the particle is measured by a unit of length rather than a percentage.
In the instant case a physical form the oil-in-water (O/W) adjuvant emulsion is in liquid initially, which is presented as a particle of a droplet.
According to the disclosures by Figures legends and the Figure drawings of the instant Application, the claimed O/W emulation adjuvant are presented as droplets or particles. The sizes the droplets (Fig. 1) and particles (Figs.2-10 ) are all measured and presented by the length units in nm µm and mm for their diameters,
While there is a distribution by different density in drawings Fig. 1A and 6A and distribution by different size of the particles But they are all less than 20% for the density and none of the them are presented as 40 to 100%, however, it is seems by volume rather than weight vs particles of the O/W emulsion.
Therefore, the claimed particle, particle size and distribution of particle size 40-100% (W/W) cited in Claim 4 need to be amended . Because it is unclear how the ratio of 40-100% (W/W) is calculated? which potion(s) or component(s) of the O/W adjuvant emulation formulation is the nominator and which one is denominator?
The rejection of Claim 5 has bene removed necessitated by Applicants’ amendment.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(Moot) The rejection of Claims 1, 3, 6, 8, 9, 10 and 12 under 35 U.S.C. 102 (a) (1) as being anticipated by Dhghan et al. (International Journal of Pharmaceuticals, Volume 475, Issues 1–2, 20 November 2014, Pages 1-8) has been moot in view of a new ground of rejection necessitated by Applicants’ amendment.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The rejection of Claims 1-3, and 8-12 under 35 U.S.C. 103 as obvious over CA 2533581C to PARISOT et al. and Amorim et al. (Pharm Res 2008 Mar 13;25(6):1256–1273) has been moot in view a new ground of rejection necessitated by Applicants’ amendment.
(New ground of rejection): Claims 1, 3- 6, 8-10, 11-12 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Garmise et al. (AAPS Pharm. SciTech,. 2006, Vol. 7 (1), pp. E1-E7).
Garmise et al. teach an influenza virus vaccine composition and a method for making and using the same. The composition of the oil-in-water adjuvant and the vaccine, is prepared as a dry powder after lyophilization. In particular, the composition comprises two portions of the major components. The first potion is the whole inactivated influenza virus (WIIV) and the second part is a mucoadhesive compound suitable for nasal delivery. The first portion of the Powders containing WIIV 100 µg either with lactose or trehalose 10 mg were produced by lyophilization (0.1/10 or about 90% w/w for saccharide/total weight ). The second part is the oil-in water emulsion comprising an adjuvant in a micro-ball mill was used to reduce the lyophilized cake to sizes suitable for nasal delivery. The second portion of the composition is the mucosal adhesive adjuvant made by Chitosan flakes milled and seized and prepared with white oil as an oil-in-water emulsion The Milled powders were seized between 45 and 125 as micro aggregate. The two portions of the powders were blended together. (Abstract).
Lyophilization composition yields approximately 37% of particles in the 45 to 125 microm particle in size and the composition also comprises other components including 1% Wt/Wt Span 80 (Detergent). The mucoadhesive compound Chitosan is roughly in 2 to 4 mm in size initially and further sized by laser diffraction and integral is stirred with a 1% (w/w) of Span80 (detergent) and light white mineral oil, via sonication for 5 minutes and then placed into the sample dropwise at the time until a laser obscuration between 2% and 30% was achieved, which results in the microparticle at the median diameter (D50) and the span ([D90-D10]/D50) etc. This process results in the Chitosan as an microparticle in an oil-in water emulsion. (Sections of
Therefore, the disclosures meet the limitations of claims 1, 3-6, 8-10, 11-12.
(New ground of rejection): Claims 1-3, 5 and 8-14 are rejected under 35 U.S.C. 102(a) (1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Iyer et al. (Journal of Pharmaceutical Sciences, Volume 106, Issue 6, June 2017, Pages 1490-1498) for claim 6 in view of the teaching by Vogel et al. (Expert Review of Vaccines, 2009, pages 483-492).
Iyer et al. teach a vaccine composition comprises subunit antigen and an adjuvant in an oil-in-water emulsion. They teach that composition comprises an antigen that can be any pathogenic antigen, which is preferably presented in example is the respiratory syncytial virus fusion protein (RSV sF) and Epstein Barr Virus glycoprotein 350 (EBV-gP350) is 5 µg, MPLA or PHAD 5mg, Saccharide 5 to 20% (w/w) and 1.5% of squalene 1.5% w/w (Section of Materials and Methods). This percentage meets the limitation that the O/W composition comprising 0.3 to 27.5 w/w/ of excipient.
The composition were previous and currently presented as squalene-based oil-in-water emulsion, and other pharmaceutical accept excipients including Histidine, sodium acetate, sodium citrate, sodium phosphate, sucrose, polysorbate-80, and other reagents were purchased from Sigma-Aldrich (St. Louis, MO). Squalene was obtained from Acros Organics (Geel, Belgium); MPLA and its synthetic analog, phosphorylated hexaacyl disaccharide (PHAD), were obtained from Avanti Lipids (Alabaster, AL). In particular, the liquid emulsions were made using squalene and several different excipients such as sucrose, trehalose and in combinations with mannitol and then lyophilized. All excipient combinations formed an elegant cake structure on lyophilization. (Second paragraph of Results).
For making an lyophilization of the emulsion, An antigen solution containing a 2× concentration (of the final dose) of the selected antigen (soluble form of RSV sF or EBV-gp350) with a stabilizing buffer was prepared. The stabilizing buffer contained 20-mM histidine/histidine-HCl, and 10% (w/v) sucrose. In a 3-mL vial (type I borosilicate glass, Schott), 0.5 mL of the antigen solution was added with 0.5 mL of the emulsion adjuvant and stoppered halfway to enable sublimation of the ice during the lyophilization process. The dilution of the emulsion adjuvant with the antigen results in a solution with a final squalene concentration of 1.5% (w/w), half of oil concentration in liquid vials (3% w/w). However, the oil-in-water emulsion adjuvant comprising squalene selected from the following concentration: 2 mg/mL, 1 mg/mL, 0.5 mg/mL, 0.2 mg/mL, and 0.1 mg/mL. Test samples were diluted 100-fold in 80%. The adjuvant composition also comprises Four different excipient combinations were also tested—10% sucrose, 10% trehalose, 5% sucrose with 2% mannitol, and finally, 5% trehalose and 2% mannitol. Taken together the monosaccharide and disaccharide are 7-20% respectively for the two testes. (See section of Development of the lyophilized Method).
Moreover, regarding claims 5 and 14, because the cited limitation of the percentage is about” 40 to 90%, the saccharase weight after lyophilization compared with the antigen 5µg would be more than at least 40 to 90%. Inherently.
Therefore, the cited reference anticipates claims 1, 3, 5, 8-11 and 12-14.
However, the cited reference does not specifically teach that the antigen is influenza viral antigen cited in claim 6.
Vogel et al. teach lone before the current Application was filed, in 2009, three types of inactivated influenza vaccines are currently in use – whole-virion (WV), split-virion (SV) and subunit (SU) vaccines. Two of these vaccine preparations, WV and SV, can contain a portion of their HA antigens as whole inactivated virions, while SU vaccines contain only HA and NA and are generally devoid of whole inactivated influenza virions. All three types of inactivated influenza vaccines have been shown to have a good safety profile and to be effective against seasonal influenza in a healthy adult population that is, at least in part, immunologically primed to the circulating influenza A and B strains, which including the influenza SU used with O/W emulsion. (See Abstract, 2nd paragraph of the review).
Therefore, alternatively, it would have been obvious for any person ordinarily skilled in the art to be motived to combine the cited references Iyer and Vogel et al. to make the stabilized dry influenza vaccine composition taught by Vogel with an antigen of influenza virus to using the science and technology taught by the cited reference , hereby producing a dry oil-in-water (O/W) emulsion composition by lyophilizing the influenza vaccine with an oil-in water formulation in order to protect the stability of the influenza virus vaccine.
As there are no unexpected results have been provided, hence the claimed invention as a whole is prima facie obvious absence unexpected results.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
BAO Q. LI
Examiner
Art Unit 1671
/BAO Q LI/ Primary Examiner, Art Unit 1671