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 .
Reopening of Prosecution
In view of the appeal brief filed on May 4, 2026, PROSECUTION IS HEREBY REOPENED. New grounds of rejections are set forth below. To avoid abandonment of the application, Applicant must exercise one of the following two options:
(1) file a reply under 37 CFR 1.111 (if this Office action is non-final) or a reply under 37 CFR 1.113 (if this Office action is final); or,
(2) initiate a new appeal by filing a notice of appeal under 37 CFR 41.31 followed by an appeal brief under 37 CFR 41.37. The previously paid notice of appeal fee and appeal brief fee can be applied to the new appeal. If, however, the appeal fees set forth in 37 CFR 41.20 have been increased since they were previously paid, then Applicant must pay the difference between the increased fees and the amount previously paid.
A Supervisory Patent Examiner (SPE) has approved of reopening prosecution by signing below:
/Michael Allen/Supervisory Patent Examiner, Art Unit 1671
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on May 4, 2026. Claims 71-72, 75-77, 80-87, 89 and 91-102 are pending and currently examined.
Interpretation of Claims
Independ claim 1 recites:
“A vaccine composition comprising antigens from at least three different strains of influenza virus and at least 19.5 mg of squalene, wherein the vaccine composition is a single-dose formulation.”
Independent claim 93 recites:
“A method of inducing an immune response in a human, comprising administering to the human a single-dose vaccine composition comprising antigens from at least three or four different strains of influenza virus and at least 19.5 mg of squalene, and wherein the human is at least 65 years of age.”
Independent claim 100 recites:
“A method for producing a vaccine composition, comprising admixing antigens from at least three or four different strains of influenza virus and at least 19.5 mg of squalene an oil-in-water emulsion adjuvant, wherein the vaccine composition is a single-dose formulation.”
The claims recite “single-dose formulation” or “single-dose vaccine composition”. Even though the claims specify that the vaccine composition is a single-dose formulation or single-dose vaccine composition, they do not specify the antigen amount, nor do they specify the volume of the “single-dose formulation” or “single-dose vaccine composition”. Therefore, the claimed vaccine composition can read on any formulation or composition of a multivalent influenza vaccine that can possible be considered (or referred to) as a “single-dose formulation” or “single-dose vaccine composition”. Indeed, the instant specification indicates that the claimed vaccine formulation/composition in a single-dose form may contain higher than standard values in both the antigen amount and volume per dose. See claims 76 and 102.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 75-77, 81-83, 85, 94, 96, 97 and 99 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
These claims recite “a standard-dose adjuvanted multivalent influenza vaccine” which renders the claims indefinite. The term “standard” is considered as a relative term. The term is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Although the specification uses the term “standard-dose adjuvanted multivalent influenza vaccine” throughout the text, it does not provide a clear and exclusive definition of this phrase or the term “standard”. The specification teaches that standard-dose multivalent influenza vaccines are well known in the art. In at least one aspect, standard-dose multivalent influenza vaccines are generally recognized by FDA (see, e.g., www.fda.gov/BiologicsBloodVaccines/ GuidanceComplianceRegulatory Informatio n/Post-MarketActivities/LotReleases/ucm062928 .htm) and nominally contain 15 μg of HA per strain per dose. For example, the trivalent TIV used in Example 1 contains 15 μg of HA from each of A/California/7/2009 (HlNl) pdm09-like virus, A/Texas/50/2012 (H3N2)-like virus, and B/Massachusetts/2/2012-like virus. See [0075].
The specification teaches embodiments for “a standard-dose adjuvanted multivalent influenza vaccine”: it may comprise anywhere between about 5 μg to about 30 μg HA antigens from each of four influenza strains (see [0083]). The specification teaches that the standard-dose adjuvanted multivalent influenza vaccine may comprise a squalene-in-water emulsion adjuvant having 9.75 mg squalene (see [0101]). The specification teaches that, in accordance with preferred embodiments, the standard-dose adjuvanted multivalent influenza vaccine comprises about 15 μg from hemagglutinin (HA) from each of the influenza virus strains, and that, in additional preferred embodiment, the standard-dose adjuvanted multivalent influenza vaccine comprises at least about 15 μg from hemagglutinin (HA) from each of the influenza virus strains. See [0082]. Accordingly, although the term “standard-dose adjuvanted multivalent influenza vaccine” is commonly used in the field and commercially, its definitions vary according to specific vaccine products, with components varying from product to product. The presence of multiple interpretations renders the claims indefinite.
Moreover, claims 81-83 specify amounts for vaccine antigen HA following the term “about” which is also a relative term and renders the claims indefinite because it is not clear how much a deviation from the specified values the term “about” allows. Additionally, claim 97 recites “wherein preferably the administration of the vaccine composition induces an immune response in the human without increase in systemic solicited adverse events compared to an administration of a standard-dose adjuvanted multivalent influenza vaccine.” Here, the term “preferably” renders the claim indefinite since it is not clear if the limitation modified by “preferably” is required or not. See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) ("[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.").
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 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
(Previous Rejection – Withdrawn) Claims 71-72, 75-77, 80-87, 89 and 91-102 are rejected under 35 U.S.C. 103 as being unpatentable over Contorni et al. (US 2012/0076822 A1, published on Mar. 29, 2012).
This rejection is withdrawn in favor of the new rejection below.
(New Rejection) Claims 71-72, 75-77, 80-87, 89 and 91-102 are rejected under 35 U.S.C. 103 as being unpatentable over Contorni et al. (US 2012/0076822 A1, published on Mar. 29, 2012) in view of Robertson et al. (EXPERT REVIEW OF VACCINES, 2016, VOL. 15, NO. 12, 1495–1505) and Van Nest et al. (US 6,299,884 B1, patent date Oct. 9, 2001). All of these references are of record in the previous Office action.
These claims are described above in “Interpretation of Claims”.
Contorni teaches that influenza vaccines include hemagglutinin from at least one influenza A virus strain and at least one influenza B virus strain. The vaccines also include an oil-in-water emulsion adjuvant with submicron oil droplets, comprising squalene. In some embodiments the hemagglutinin concentration is >12 μg/ml per strain. In some embodiments the squalene concentration is <19 mg/ml. In some embodiments the vaccine is mercury free. In some embodiments the vaccine has a unit dose volume between 0.2-0.3 mL. In some embodiments the squalene concentration is 9.75 mg/mL or 4.88 mg/mL. In some embodiments the vaccine includes antigens from two influenza A virus strains and two influenza B virus strains. See Abstract.
Contorni teaches a trivalent seasonal influenza vaccine, FLUAD™. The adjuvant in the trivalent seasonal FLUAD™ vaccine is an oil-in-water emulsion. The antigen and the emulsion adjuvant are supplied in pre-mixed format in a pre-filled syringe. They teach that its product datasheet shows that each dose has a volume of 0.5 mL and contains 15 μg hemagglutinin (HA) per strain with 9.75 mg squalene and 1.175 mg polysorbate 80. The vaccine is made by mixing at a 2x emulsion with a 2x antigen solution at a 1: 1 volumetric ratio, to give a final solution with both emulsion and antigen at the 1 x concentration. See [0005].
Contorni teaches that in the FLUAD™ vaccine the total amount of HA is 45 μg (3x15 μg) and the total amount of squalene is 9.75 mg, in a dosage volume of 0.5 ml (i.e. 19.5 mg/ml squalene). In the PREP AND RIX™ vaccine the total amount of HA is 3.75 μg (monovalent) and the total amount of squalene is 10.68 mg, also in a dosage volume of 0.5 ml (i.e. 21.4 mg/ml squalene). In many embodiments of the invention the squalene concentration is less than 19 mg/ml while still retaining an adjuvant effect, and the concentration may be ~10 mg/ml, e.g. ~5 mg/ml, ~2.5 mg/ml. A minimum amount of 0.5 mg squalene per dose is useful (e.g. see ref. 3). Examples of amounts per dose include 5.3 mg, 4.9 mg, 2.7 mg, 2.4 mg, 1.2 mg etc. See [0078].
Contorni teaches that a submicron emulsion of squalene, polysorbate 80, and sorbitan trioleate may contain by volume about 5% squalene, about 0.5% polysorbate 80 and about 0.5% Span 85. In weight terms, these ratios become 4.3% squalene, 0.5% polysorbate 80 and 0.48% Span 85. This adjuvant is known as 'MF59'. See [0085].
Contorni further teaches that mixtures of oils can be used e.g. squalene and a-tocopherol, and that an oil content in the range of 2-20% (by volume) is typical. See [0080]. Contorni teaches that a submicron emulsion of squalene, a tocopherol, and polysorbate 80 may have from 2 to 10% squalene, from 2 to 10% tocopherol and from 0.3 to 3% polysorbate 80, and the weight ratio of squalene: tocopherol is preferably ~1 (e.g. 0.90) as this can provide a more stable emulsion. See [0086].
Accordingly, teachings of Contorni indicate that various squalene amounts and/or concentrations can be used in making squalene-containing emulsions used in influenza vaccines, with a squalene concentration as high as 21.4 mg/ml squalene. By teaching that oil content in an emulsion can be in the range of 2-20%, Contorni suggests that concentration of squalene can also be in this range since squalene is the only oil component of many oil-containing emulsions used as adjuvant. Taking the squalene content in MF59 of about 5% (v/v) or 4.3% (w/v) squalene which corresponds to about 10 mg per dose in 0.5 ml volume of the total vaccine, 20% squalene can be equivalent to about 40 mg per dose1.
Robertson is a review article on Fluzone, a high-dose influenza vaccine. It teaches that Fluzone® High-Dose (IIV3-HD) is a trivalent, inactivated, split-virus influenza vaccine indicated for use in older adults (≥65 years of age). It contains 60 μg hemagglutinin of each influenza strain, which is four times the hemagglutinin content of standard-dose influenza vaccines, including Fluzone (IIV3-SD). IIV3-HD has been licensed for use in older adults in the US since December 2009 and in Canada since February 2016. Robertson teaches that multiple studies conducted since 2004 have consistently shown that, in older adults, IIV3-HD induces substantially greater antibody responses and better protection against influenza and influenza-associated hospitalization than IIV3-SD. Health economic analyses suggest that IIV3-HD can be a cost-effective alternative to standard-dose trivalent or quadrivalent inactivated influenza vaccines and can even be cost-saving compared to IIV3-SD in older adults. Further investigation of IIV3-HD vaccination as a way to improve immune responses and protection against influenza in immunocompromised individuals is warranted. See Abstract.
Accordingly, Robertson teaches a trivalent influenza virus vaccine for administration to elderly subjects over 65 years of age and that the vaccine may have up to four-fold higher influenza antigens than those of a standard-dose influenza virus vaccine. Teachings of Robertson suggest that influenza vaccines do not have to contain a “standard dose” of antigens. They also demonstrate that dose is a result effective variable.
Van Nest teaches that in a series of experiments, hamsters were immunized with a commercial influenza vaccine from Instituto Vaccinogeno Pozzi. This vaccine consists of purified HA from two A strains (A/Leningrad/360/86 and NSingapore/6/86) and one B strain (B/Ann Arbor/1/86). The vaccine was tested alone, with an MTP-PE/LO emulsion made with a Kirkland emulsifier (Fluoromed Pharmaceutical, Inc., La Mesa, Calif.) and with an MTP-PE/MF emulsion made in a microfluidizer (model 11OY, Microfluidics, Newton, Mass.). The first two are comparative compositions, while the "MF" composition is a composition of the invention. MTP-PE/MF stands for "MTP-PE Microfluidizer" emulsion and contains 4% squalene and 1.0 mg/ml MTP-PE emulsified with the Microfluidizer. The MTP-PE Kirkland emulsion contained 4% squalene, 0.5 mg/ml MTP-PE, and 0.008% Tween 80 MF-68+MTP-PE, and the Ribi Adjuvant system made in the emulsified with the Kirkland emulsifier. Animals received three immunizations containing 8.3 μg of each HA antigen. MTP-PE was used at 50 μg per dose in both formulations. See columns 26, line 58-column 27, line 7.
Van Nest teaches that teaches that in further experiments, the immunogenicity of two commercial influenza vaccines, Parke-Davis Fluogen and Duphar subunit influenza, were compared with no adjuvant and with several MTP-PE containing adjuvant formulations in goats. The animals were immunized intramuscularly with 0.5 ml of each vaccine mixed with either 0.5 ml of PBS or 0.5 ml of MTP-PE adjuvant formulations. Animals received 0.5 ml of vaccine mixed with either 0.5 ml of PBS or 0.5 ml of the indicated adjuvant formulation to generate a 1.0 ml injection volume. See column 27, lines 33-50.
Accordingly, teachings of Van Nest indicate that influenza virus vaccines, including trivalent influenza virus vaccines comprising squalene-containing adjuvants, does not have to be administered in a dose volume of 0.5 ml or less. Instead, they can be administered in higher volumes, such as 1 ml, according to experimental needs.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to combine the teachings of Contorni, Robertson and Van Nest to arrive at the invention as claimed. E.g., one of skill in the art would have found it obvious to increase the volume of a 0.5-ml vaccine of Contorni (e.g. the trivalent seasonal FLUAD™ which contains 15 μg hemagglutinin (HA) per strain with 9.75 mg squalene and 1.175 mg polysorbate 80 per 0.5 ml dose) to 1 ml so that the vaccine influenza antigen amount can be increased for each administration, based on the teachings of Robertson and Van Nest. In this case, the squalene amount in one “single-dose” formulation is doubled. E.g., for the FLUAD™ vaccine, a 1 ml “single-dose formulation” would contain 9.75x2=19.5 mg. Here, this amount leads to the invention of claim 93, when such a vaccine is administered to a population of 65+ years of age.
Additionally, according to section 2144.05 of the MPEP, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”). This applies to the amount of adjuvant and antigen as well as squalene since squalene amount can clearly be varied in the prior art and it is a result effective variable because one of skill in the art would have expected that immunogenic effects produced by different amounts of squalene and antigen can be tested by routine experimentation, and the ranges as claimed can be obtained in the routine experimental optimization process.
Regarding claims 75-77, 81-83 and 85, which recite values of antigen amount, one of skill in the art would have found it obvious to arrive at the values via routine experimental optimization, including increasing or reducing antigen amount, based study needs, unless there is evidence that the claimed antigen amounts are critical. High-dose vaccines are often tested in certain vaccine recipients. Thus, the values of the instant claims will be arrived at by routine experimentation in optimization of a result effective variable and the claims are obvious here.
Regarding claim 91, Contorni teaches that cell lines and chicken eggs can be used as substrate for viral growth in the manufacture of vaccines in the invention. See [0042].
Regarding claim 92, Contorni teaches that the influenza vaccine may contain hemagglutinin in the form of split virons or purified surface antigens. See [0014].
Regarding claims 94-95, which recite “wherein the administration of the vaccine composition induces a higher seroconversion rate in the human compared to an administration of a standard-dose adjuvanted multivalent influenza vaccine”, the claims are highly generic in the vaccine components with only a range of squalene specified (at least 19.5 mg or more per single dose) and an undefined “standard-dose adjuvanted multivalent influenza vaccine”. Therefore, since combined teachings of Contorni, Robertson and Van Nest lead to a multivalent “single-dose” influenza vaccine formulation with squalene in the range as claimed, one of skill in the art would have expected that a vaccine formulation that “induces a higher seroconversion rate in the human compared to an administration of a standard-dose adjuvanted multivalent influenza vaccine” can be reached through routine experimental optimization (e.g., by optimizing antigen amount), especially considering the vaccine to be compared, i.e., a standard-dose adjuvanted multivalent influenza vaccine, is not specified. Furthermore, the court has noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” Id. The wherein clauses of these claims only recite an intended result which will necessarily occur due to all method steps being met but that does not receive patentable weight.
Further regarding claim 95, which specifies “wherein the higher seroconversion rate is 67.9%”, the specification teaches that, as shown in FIG. 4, seroconversion rates were also highest in Group 4 for A/H3N2 (77.8% [95% CI 57.7 to 91.4]), followed by Group 2 (67.9% [47.6 to 84.1]) and Group 3 (64.3% [44.1 to 81.4]). Seroconversion rates for A/H1N1 were highest in Group 4 (63.0% [42.4 to 80.6]), whereas for B strain seroconversion occurred most often in Group 2 (39.3% [21.5 to 59.4]). See [0242]. FIG. 4 depicts percentage of subjects with seroconversion (pre-vaccination hemagglutination inhibition [HI] titre <10 and a post-vaccination HI titre >=40) or significant increase (pre-vaccination HI titre 0 and a minimum 4-fold rise in post-vaccination HI antibody titre) in HI titre at Day 22. T-bars represent 95% confidence intervals. See [0012].
These teachings indicate that rates seroconversion may vary with groups of study subjects and can be obtained by testing individual vaccines in subjects. Since the claim is highly generic in vaccine components, one of skill in the art would have expected that a seroconversion rate as claimed (67.9%) can be reached by modifying vaccine components such as antigen and adjuvant amounts, as well as administration process, based on the teachings of the cited references.
Regarding claims 96-98, which recite wherein clauses specifying that administration of the claim vaccine composition induces an immune response in the human without increase in unsolicited adverse events compared to an administration of a standard-dose adjuvanted multivalent influenza vaccine. It is noted that the functional limitations in the wherein clauses represent intended results only. As indicated above, the specification teaches testing of influenza vaccine of the invention in with routine processes and routes. Since the combined teachings of the cited references lead to the invention as claimed (a highly generic single-dose multivalent influenza virus vaccine formulation comprising at least 19.5 mg of squalene), one of skill in the art would have reasonably expected that the claimed effects (i.e., inducing immune response without increase in unsolicited adverse events compared to an administration of a standard-dose adjuvanted multivalent influenza vaccine) would also be able to be achieved for a multivalent vaccine with the claimed squalene amount suggested by the combined teachings of Contorni, Robertson and Van Nest, especially considering that “standard-dose adjuvanted multivalent influenza vaccine” is not clearly and exclusively defined.
With respect to claim 100, since the composition is obvious for use in vaccination as discussed above, it is equally obvious to make the obvious composition.
Response to Applicant’s Arguments
Applicant’s Arguments filed on May 4, 2026 have been fully considered and are addressed as follows.
Applicant argues that Contorni's highest disclosed single dose is 10.68 mg of squalene in a 0.5 mL volume, and that while Contorni teaches a 21.4 mg/mL squalene concentration, two 0.5 mL doses would be needed to arrive at such a concentration. Applicant thus argues that Contorni fails to teach or suggest a single-dose formulation of at least 19.5 mg of squalene, as claimed. Applicant argues that the Examiner relies on the reference's disclosure that "a range of 2%-20% of oil can be used in an adjuvant made of oil-water emulsion" to assert obviousness, which Applicant disagrees. Applicant argues that the Contorni's disclosure merely states that "[a]n oil content in the range of 2-20% (by volume) is typical" and that "[m]ixtures of oils can be used e.g. squalene and α-tocopherol", and that there is no specific mention of which specific oils Contorni envisions. Applicant argues that Contorni discloses a long list of oils that can be mixed in accordance of Contorni’s teachings. Applicant argues that even if Contorni's mixture included squalene and a-tocopherol, there is no indication of the specific amount of squalene in Contorni's 2-20% range. Applicant argues that Contorni is 10.68 mg of squalene in a 0.5 mL volume, that there is no guidance or suggestion in Contorni to employ more squalene, only that additional oils to the combination may reach 20%, that there is no indication how Contorni's weight percentage for oil content is tied to mg, as recited in the claims, and that Contorni fails to disclose a volume associated with its oil content weight percentage, such that a specific weight of an oil could actually be determined.
Applicant’s arguments above are not persuasive.
First, as indicated in the Interpretation of Claims and the rejections above, by reciting “single-dose formulation” or “single-dose vaccine composition” the claims do not limit the vaccine volume nor do they limit the antigen amount. Although teachings of Contorni suggest that a dose volume of 0.5 ml or less of influenza vaccine is routinely used, it does not teach that a vaccine dose in a volume of 1 ml or even higher cannot be administered to a subject. On the contrary, teachings of Robertson and Van Nest indicate that influenza vaccines in a dose with higher antigen amount and higher volume can be used. Therefore, one of skill in the art would have found it obvious to test the efficacy of the vaccines of Contorni (e.g., trivalent seasonal FLUAD™ which contains squalene at 19.5 mg per 0.5 ml) at a dose formulation with different of antigen amount and/or volume. This is especially true based on the teachings of Robertson and Van Nest that amount of antigen and volume of a vaccine dose can be changed. In the case of Contorni, a 1 ml dose of FLUAD™ contains 19.5 mg of squalene.
As to Applicant’s argument about Contorni’s teaching about the possible percentage range of oil content that can be used in vaccine formulation, Contorni teaches that mixtures of oils can be used e.g. squalene and a-tocopherol, and that an oil content in the range of 2-20% (by volume) is typical. See [0080]. This teaching does not limit that the oil content must be a mixture. Since in many influenza vaccines, including those disclosed in Contorni, squalene is the only oil component, a 20% (by volume) corresponds to a higher squalene amount than 19.5 mg, even in a volume of 0.5 ml.
Applicant disagrees with the Examiner’s standing that it would have been routine to arrive at a single dose of squalene at least 19.5 mg based on Contorni's teachings. Applicant argues that routine optimization requires an explanation of why it would have been routine to arrive at a claimed invention (i.e., Applicant's purportedly routine dose would have been "obvious to try"), referring to M.P.E.P. § 2144.05(II)(A-B). Applicant argues that many gaps exist between Contorni's disclosure of 2-20% oil and the claimed single dose of at least 19.5 mg, and that it would not have been routine to arrive at Applicant's claimed amount of at least 19.5 mg in a single-dose formulation, given Contorni's glaring and numerous deficiencies.
Applicant’s arguments are not persuasive. As indicated above, Contorni's disclosure of 2-20% oil does not require that oil used in a vaccine must be a mixture of different oils. On the contrary, it provides guidance for the range for oil concentrations for one of skill in the art to try in routine experimental optimization.
MPEP 2144.05(II)A states that generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. MPEP 2144.05(II)B states that in order to properly support a rejection on the basis that an invention is the result of "routine optimization", the examiner must make findings of relevant facts, and present the underpinning reasoning in sufficient detail, and that the articulated rationale must include an explanation of why it would have been routine optimization to arrive at the claimed invention and why a person of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed range.
The art rejection above establishes that Contorni teaches that different amounts of squalene have been used in influenza vaccine formulations and that different dose volumes (although 0.5 ml or less), squalene amount (although 10.5 mg per dose of 0.5 ml or less), and range of oil concentration that can be used (2-20% for total oil content). These teachings are considered sufficient for one of skill in the art to test various different squalene concentrations in the development vaccine formulations, and the claimed range of squalene amount is considered as reachable through routine experimental optimization unless there is evidence that the claimed range is critical.
To rejection of claim 102, Applicant argues that Van Nest's formulation includes a 1.6%-or .016 mg-squalene concentration (Van Nest at 27:40-45), which is significantly lower than that claimed, and that it would not have been reasonable to jump from a 1.0 mL dose comprising only 0.16 mg of squalene, as taught by Van Nest, to a 1.0 mL dose comprising at least 19.5 mg of squalene, as claimed; nor would it have been reasonable to arrive at the claimed formulation relying on Contorni's single-dose 10.68 mg squalene concentration. Applicant argues that, thus, neither Contorni nor Van Nest teaches or suggests (1) a single-dose formulation of at least 19.5 mg of squalene, as recited in the independent claims, or (2) a 1.0 mL single-dose formulation comprising at least 19.5 mg of squalene, as recited in dependent claim 102. Applicant argues that the applied references, accordingly, fail to disclose each element of the claims.
Applicant’s arguments are not persuasive. Teachings of Van Nest indicate that a single-dose formulation of multivalent influenza virus vaccine comprising squalene can be prepared and administered in the volume of 1 ml per dose. The teachings are not relied upon for the teachings of squalene amount. Contorni and Van Nest combined teach or suggest every element of the claimed invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/ Primary Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
1 See paragraphs [0078] and [0085] of Contorni et al. for the estimation of squalene amount in the MF59-adjuvanted influenza vaccine FLUAD. Paragraph [0097] of Contorni teaches that the liquids of adjuvant emulsion and the vaccine antigen are generally mixed at about 1:1 ratio.
Prosecution Insights