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
Acknowledgement is hereby made of receipt and entry of the communication filed on Aug. 25, 2022. Claims 1-8 are pending and currently examined.
Claim Objections
Claims 1-8 are objected to because of the following informalities:
The base claim 1 describes a method for producing an inactivated influenza vaccine “ the method comprising: treating a virus solution comprising an influenza virus collected from a host with β-propiolactone in advance, in an inactivation treatment using formaldehyde”, which makes the treating steps confused.
Appropriate correction is required for clarify/simplify the language.
Claim Rejections - 35 USC § 112 (b)
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 2-4 and 6-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 2 and 7-8 recite a percentage at “range of from 0.005 to 0.015 vol%” (see claim 2) or a range of from 0.0125 to 0.1 vol.% (See claims 7 and 8), where the “0.005 to 0.015 vol%” and “0.0125 to 0.1 vol.%” render the claims indefinite. It is not clear if the percentage means (Vol./Vol.) or (Vol: Vol) or other forms such as w/v.
Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
Claims 3 and 6 recite a term “ the inactivation treatment” with a claim of a specific temperature and time, where the “ the inactivation treatment” renders the claims indefinite. Based on the instant claims, the inactivation treatment comprises treating virus using β-propiolactone in advance and then using formalin, where each treatment is at different conditions. Therefore, it is unclear what the “the inactivation treatment” recited in claims 3 and 6 is referring to. For example, is it referring to the inactivation treatment using β-propiolactone, or using formalin or for both treatments?
Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
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.
Claims 1 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Andre et al. ( WO 2010/052214 A2, published on May 14, 2010).
The base claim 1 is directed to a method for producing an inactivated influenza vaccine, the method comprising: treating a virus solution comprising an influenza virus collected from a host with 3-propiolactone in advance, in an inactivation treatment using formaldehyde.
Andre et al. teaches an invention that relates to a cell culture-based method of producing influenza vaccine, which provides a method for reducing the amount and/or the size of contaminating residual nucleic acids from host cells through the implementation of at least two distinct degradation steps performed by an endonuclease, such as Benzonase TM, and/or by a DNA alkylating agent, such as beta-propiolactone (BPL), or by a combination (See page 1, lines 10-18; page 24, lines 6-11). Andre et al. teaches a step providing a composition comprising a virus, or a viral antigen by the follows:
a) providing a population of cells cultured in a cell culture medium,
(b) inoculating the population of cells with a virus,
(c) culturing the population of cells so as to allow the virus to replicate,
(d) collecting the produced virus thereby providing a viral harvest, and
(e) isolating the virus,
the method comprising at least two steps of host cell nucleic acids degradation with a compound selected from i) an endonuclease and ii) a DNA alkylating agent (See page 3, lines 1-12). At the same time, Andre et al. teaches that in a specific embodiment, the method according to the invention further comprises at least one BPL treatment step and at least one formaldehyde treatment step. Formaldehyde and BPL may be used sequentially, in any order, for instance, formaldehyde is used after the BPL (See page 21, lines 4-17). Here the description of Andre teaches that the virus composition is collected from the cell culture and treated with BPL in advanced, and then the composition is further inactivated by formaldehyde.
Regarding claims 5 , it requires producing inactivated whole-virus vaccine or split vaccine of an influenza virus. Andre et al. teaches that the immunogenic compositions, in particular vaccines, of the present invention will generally be formulated in a sub-virion form, e.g. in the form of a split virus, where the lipid envelope has been dissolved or disrupted, or in the form of one or more purified viral proteins (subunit vaccine). As an alternative, the immunogenic compositions may include a whole virus, e.g. a live attenuated whole virus, or an inactivated whole virus. (See page 19, lines 20-25).
Accordingly, claims 1 and 5 are anticipated by Andre et al.
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.
Claims 2 and 7- 8 are rejected under 35 U.S.C. 103 as being unpatentable over Andre et al. ( WO 2010/052214 A2, published on May 14, 2010) as applied to claims 1 and 5 above and as evidenced by DUKE-Light Microscope Core facility.
Regarding claim 2, it requires that the inactivation treatment comprises adding formalin to the virus solution at a final concentration in a range of from 0.005 to 0.015 vol %.
Andre et al. teaches that formaldehyde was added to detergent-inactivated pool of viruses to further inactivate the virus. Formaldehyde is added at a ratio of 50 μg for 250 μg total proteins (See page 29, lines 11-15). It is a common knowledge in the art that Formaldehyde, also known as methanal or formalin, is a simple organic compound with a chemical formula of CH2O. This can be evidenced by DUKE-Light Microscope Core facility (https://microscopy.duke.edu/guides/paraformaldehyde-formaldehyde-formalin ). DUKE teaches that formalin is the name for saturated (37%) formaldehyde solution. Thus, a protocol calling for 10% formalin is roughly equivalent to 4% formaldehyde (See page 1, paragraph 1). Because the same inactivation reagent and the same virus are used in both Andre and the instant application, a claimed concentration can be achieved through experimental optimization unless there is evidence showing that the claimed concentration can produce unexpected results.
In addition, 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.”).
Regarding claims 7 and 8, they require that the method of claim 2 or claim 3, further comprising: a β-propiolactone treatment comprising adding the [β-propiolactone to the virus solution comprising collected influenza virus to a final concentration in a range of from 0.0125 to 0.1 vol.% and a reaction at a temperature in a range of from 2°C to 8°C for 18 hours or longer. Andre et al. teaches that the method according to the present invention is not limited to a single use of BPL, but also contemplates, as described above, more than one BPL step. BPL can be added at any suitable step of the present method (See page 19, lines 1-8). Also, Andre et al. teaches that the BPL is used at a concentration ranging from 0.01 % to 0.1 % at a temperature ranging from 2 to 8°C, and the incubation time varies (See page 18, lines 30-38). Because the concentration and the incubation time of Andre is comparable with the claim, the incubation time should be similar.
Claims 3 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Andre et al. ( WO 2010/052214 A2, published on May 14, 2010) as evidenced by DUKE-Light Microscope Core facility as applied to claims 1-2, 5 and 7-8 above, and in view of Sanders et al. (Vaccine Analysis: Strategies, Principles, and Control. 2014 Nov 28:45–80).
Regarding claim 3, it requires that the inactivation treatment is performed by a reaction at a temperature in a range of from 20C to 80C for a duration in a range of from 3 to 14 days. Andre et al. teaches that the formaldehyde incubation lasts 72 hours at room temperature in sterile conditions. Because Andre et al. teaches using the same reagent of formaldehyde to inactive the same virus, if the temperature is adjusted to the 20C to 80C as claimed, a 3 to 14 days incubation time would be achieved through experimental optimization unless there is evidence showing that the claimed temperature and duration can produce unexpected results.
Nevertheless, Sanders et al. teaches that methods for formaldehyde inactivation vary greatly between vaccines. Differences lie in formalin concentrations (from 0.08 to 0.009 % w/v), time of inactivation (from days to months), and temperature (usually 4 or 37 °C) (See page 57, paragraph 2). It would be obvious for one of ordinary skill in the art to test a time and temperature using the same inactivation reagent such as BPL and formalin to inactive the influenza virus as claimed, and the result would be predictable based on the teachings from Andre and Sanders.
Regarding claim 6, the inactivation treatment is performed by a reaction at a temperature in a range of from 20 to 30°C for 3 days. Andre et al. teaches the same inactivated influenza vaccine and the same inactive procedure and same inactive agents as claimed in the instant application. The temperature and duration for the inactivation treatment should be same at the same condition. If the temperature is adjusted to the 20 to 30°C as claimed, a 3 days incubation time would be achieved through experimental optimization unless there is evidence showing that the claimed temperature and duration can produce unexpected results. Also, Andre et al. teaches that the conditions of viral inactivation may vary and will be determined, in particular, by assessing the residual virus infectivity by measuring the Tissue Culture Infectious dose (TCID50/ml) (See page 21, lines 15-17).For example, BPL is suitably incubated for an overnight period. BPL is active in a wide range of temperature. In one embodiment of the present invention, BPL is incubated at a temperature ranging from 2 to 8°C. In a distinct embodiment, BPL is incubated at room temperature (See page 18, lines 35-38), and formaldehyde can be used to inactive virus at 72 hours at room temperature (See page 29, lines 11-15). Here these teachings indicate that a range pf optimized conditions at certain temperature from Andre can be achieved and they all successfully inactive viruses.
In addition, 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.”). Therefore, the condition of “at a temperature in a range of from 20 to 30°C for 3 days” is taught by Andre through a routine experimental optimization.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Andre et al. ( WO 2010/052214 A2, published on May 14, 2010) as applied to claims 1 and 5 above.
Regarding claim 4, it requires the method of claim 1 further comprising a β-propiolactone treatment comprising adding the β-propiolactone to the virus solution comprising collected influenza virus to a final concentration in a range of from 0.0125 to 0.1 vol.% and a reaction at a temperature in a range of from 20C to 80C for 18 hours or longer.
Andre et al. teaches that the method according to their invention is not limited to a single use of BPL, but also contemplates, as described above, more than one BPL step. BPL can be added at any suitable step of the present method (See page 19, lines 5-7), and BPL is used at a concentration ranging from 0.01 % to 0.1 % at a temperature ranging from 2 to 8°C, and the incubation time vary (See page 18, lines 30-38). Because Andre et al. teaches the same BPL concentration and the incubation temperature, a reaction of 18 hours or longer can be reasonable achieved based on the needs.
In addition, 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.”). Here, the incubation time of Andre was sufficient to inactivate virus. Therefore, determining other workable or optimal incubation times is routine experimentation.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am..
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/RUIXUE WANG/Examiner, Art Unit 1671
/NICOLE KINSEY WHITE/ Primary Examiner, Art Unit 1671