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 .
Claim Objections
Claims 1, 8, 16, 25, and 26 are objected to because of the following informalities:
Articles preceding nouns, i.e., “a” and “the”, are missing in claims 1, 8, 25, and 26.
In claims 1, 8, and 26, “upto” should be two words.
Additionally, “PBL”, recited in claim 8 should be “BPL”.
Appropriate correction is required.
Applicant is advised that should claim 1 be found allowable, claim 25 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). No difference is scope is apparent.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2, 3, and 16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 2 requires the inactivated SARS-CoV-2 that is killed. Instant claim 1 already requires the SARS-CoV-2 that is inactivated, i.e., killed. Therefore, claim 2 fails to further limit the subject matter of claim 1. Instant claim 3 requires a Vero cell, which is an African Green Monkey cell. Vero cells, i.e., African Green Monkey cells, are already recited in instant claim 1. Therefore, claim 3 fails to further limit instant claim 1. Instant claim 16 requires the inactivated, i.e., killed, SARS-CoV-2, used as an active ingredient in an immunogenic composition. Claim 1 requires preparation of a coronavirus vaccine by preparing an inactivated, i.e., killed SARS-CoV-2. Claim 16 fails to further limit claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-25 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 1 and 25 recite “(with and without serum)”. Due to the presence of parentheses, it cannot be determined whether the phrase is a recited limitation or not. If the parenthesized phrase is intended to be a limitation, the absence or presence of serum, is contradictory and therefore, incomprehensible. This rejection affects all dependent claims.
Claims 2 and 16 recite “inactivated” and “killed-inactivated”, and claims 17, 22, 25, and 27 recite “killed-inactivated”. Since “killed” and “inactivated” are synonyms, it is unclear what is intended by recitation of the two terms.
Instant claim 3 requires a Vero cell, which is an African Green Monkey Kidney cell. Therefore, African Green Monkey Kidney cells are broader in scope than the Vero cells of claim 1, from which claim 3 depends. It is unclear if a different limitation, other than African Green Monkey Kidney Vero cells are intended.
Regarding claims 8, 18, and 26, the recitation of “preferably” renders the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 13 contains the trademark/trade name, “Cellufine”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an affinity chromatography component and, accordingly, the identification/description is indefinite.
Claim 22 recites, “Phosphate buffered saline as antigen”. However, phosphate buffered saline is not art-recognized as antigenic and the claim is indefinite.
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.
Claim 27 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (bioRxiv. 2020 Aug 4: 2020-08).
Chen et al. anticipate a method of protecting rhesus macaques by administering an inactivated, purified SARS-CoV-2 by intramuscular inoculation, see the title and “Immunization of rhesus macaques with the SARS-CoV-2 inactivated vaccine elicits effective immunity with indexes of humoral and cellular reactions”, anticipating instant claim 27.
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.
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.
Claim 24 is 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 Chen et al. supra.
Claim 24 is drafted in a product-by-process format. Chen et al. teach a method of preparing the inactivated SARS-CoV-2 vaccine by using Vero cells as a substrate for SARS-CoV-2 culture, inactivating the viral harvest with formaldehyde and beta-propiolactone, and purifying the virus in “Virus and cells” and “Inactivated vaccine”.
Chen et al. do not describe the production of the SARS-CoV-2 vaccine by scaling up the volume to 10L. However, the recitation of the process limitations in claim 1 is not viewed as positively limiting the claimed SARS-CoV-2 vaccine, absent a showing that the process of making recited in claim 1 imparts a novel or unexpected property to the claimed product, as it is assumed that equivalent products are obtainable by multiple routes. There are no additional structural limitations recited.
In product-by-process type claims, the process of producing the product is given no patentable weight since it does not impart novelty to a product when the product is taught by the prior art. See In re Thorpe, 227 USPQ 964 (CAFC 1985); In re Marosi, 218 USPQ 289, 292-293 (CAFC 1983) and In re Brown, 173 USPQ 685 (CCPA 1972). Consequently, even if a particular process used to prepare a product is novel and unobvious over the prior art, the product, per se, even when limited to the particular process, is unpatentable over the same product taught in by the prior art. See In re King, 107 F.2d 618, 620, 43 USPQ 400, 402 (CCPA 1939) and In re Merz, 97 F.2d 599, 601,38 USPQ 143-145 (CCPA 1938). Therefore, since the instant products and those of Chen et al. are indistinguishable from the process by which they are made, Chen et al. anticipates or renders the instant coronavirus vaccine prima facie obvious, absent unexpected results to the contrary.
The burden is upon the applicants to establish a patentable distinction between the claimed and referenced products.
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 1-13, 16-18, 25, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. supra and Gao et al. et al. (WO 2021/209060, 17 April 2020 priority date).
Chen et al. teach a method of preparing the inactivated SARS-CoV-2 vaccine by using Vero cells as a substrate for SARS-CoV-2 culture, inactivating the viral harvest with formaldehyde and beta-propiolactone, and purifying the virus by Core-700 gel, a multimodal chromatography resin that combines both size exclusion and affinity chromatography in one bead in “Virus and cells” and “Inactivated vaccine”, as required by instant claims 1-3, 7, and 11-13. In the section, “Inactivated vaccine”, Chen et al. teach combining the killed SARS-CoV-2 vaccine with 0.5 mg of Al(OH)3, as required by instant claims 16-18.
Chen et al. do not describe the production of the SARS-CoV-2 vaccine by scaling up the harvest volume to 10 L, as recited in instant claims 1 and 25.
Gao et al. teach scaling up a harvest volume of at least 10 L in paragraph [0050].
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have scaled up the SARS-CoV-2 culture of Chen et al., as taught by Gao et al., to achieve a large quantity of virus for vaccine production prior to inactivation. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have scaled up the SARS-CoV-2 culture of Chen et al., as taught by Gao et al., to achieve a large quantity of virus for vaccine production because both Chen et al. and Gao et al. teach propagation of virus for SARS-CoV-2 vaccine production in Vero cells, see “Virus and cells” and “Inactivated vaccine” of Chen et al. and claims 1, 2, 12, 13, 25, and 41 of Gao et al.
Chen et al. do not mention a temperature for the Vero cell culture ranging between 33°C to 37°C, as recited in instant claim 4; or a multiplicity of infection (m.o.i.) ranging from 0.001 to 0.1, recited in claim 5; or the harvest time ranges between 48-80 hours post infection of Vero cells, recited in instant claim 6.
Paragraph [0019] of Gao et al. teach SARS-CoV-2 is cultured in Vero cells in a bioreactor at 35-39°C for 3-7 days, overlapping with the temperature and time ranges recited. Paragraph [0137] and Figure 1B of Gao et al. teach the m.o.i. of 0.0001-0.01 is reached after 3-4 days post infection at temperatures between 33°C-37°C.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have incubated the Vero cells in a bioreactor at 35-39°C for 3-7 days to reach an m.o.i. of 0.0001-0.01 in the method of propagation taught by Chen et al. to achieve a high viral titer for vaccine production. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have incubated the Vero cells in a bioreactor at 35-39°C for 3-7 days to reach an m.o.i. of 0.0001-0.01 in the method of propagation taught by Chen et al. because Chen et al. and Gao et al. produce an inactivated SARS-CoV-2 vaccine by culturing the virus in Vero cells prior to inactivation, see “Virus and cells” and “Inactivated vaccine” of Chen et al. and paragraphs [0019, 0137] and Figure 1B of Gao et al.
In the “Inactivated vaccine” section, Chen et al. teach the viral harvest is inactivated with formalin at a rate of 1:4000 for 48 hours, which is followed by a second inactivation at 1:2000 with beta-propiolactone.
However, Chen et al. do not teach the temperatures corresponding to each inactivation, recited in instant claims 8-10 and 26.
Gao et al. teach β-propiolactone inactivation concentration ranging from 1 :4000 for 16-72 hours for 20-24 hours at 4°C in paragraph [0044] and formalin inactivation concentration ranging between 1:1000-1:4000 for s 3-72 hours at 4°C in paragraph [0045], overlapping with the requisite limitations. Also see claims 1, 2, 25, and 28-30.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have inactivated the SARS-CoV-2 by the parameters taught by Gao et al. in the method of Chen et al. to ensure complete inactivation of the virus. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have inactivated the SARS-CoV-2 by the parameters taught by Gao et al. in the method of Chen et al. because both Chen et al. and Gao et al. teach inactivating SARS-CoV-2 with β-propiolactone and formalin, see the “Inactivated vaccine” section of Chen et al. and claims 1, 2, 25, and 28-30 of Gao et al.
Claims 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. and Gao et al. as applied to claims 1-13, 16-18, and 24-27 above, and further in view of Rappuoli et al. (USPgPub 2006/0257852).
See the teachings of Chen et al. and Gao et al. et al. above. Chen et al. teach purifying the virus by Core-700 gel, a multimodal chromatography resin that combines both size exclusion and affinity chromatography in one bead in “Virus and cells” and “Inactivated vaccine”. Claims 3, 4, 16, 17, 26, 27, and 35, Gao et al. recite ion-exchange chromatography and/or size exclusion chromatography as purification steps of the inactivated SARS-CoV-2. However, neither Chen et al. nor Gao et al. teach ultracentrifugation and tangential flow filtration, as recited in claims 14 and 15, respectively.
Rappuoli et al. teach purifying SARS by ultracentrifugation and tangential flow filtration, see paragraphs [0579, 0674, 0777] and claims 42, 50-52, and 56.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have purified the SARS-CoV-2 of Chen et al. and Gao et al. by ultracentrifugation and/or tangential flow filtration steps of Rappuoli et al. with a reasonable expectation of success because SARS-CoV-2 is a SARS virus and Rappuoli et al. combine either or both of these purification methods with various chromatography techniques in paragraphs [0579, 0674, 0777] and claims 42, 50-52, and 56 after inactivating the virus with formalin and/or β-propiolactone in paragraph [0561] and claims 22 and 29-31, that had been cultured in Vero cells prior to inactivation, see claims 42 and 44.
Claims 19, 20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. and Gao et al. as applied to claims 1-13, 16-18, and 24-27 above, and further in view of Starzl (USPgPub 2021/0347858, priority to 3 April 2020).
See the teachings of Chen et al. and Gao et al. above. Neither reference mentions the stabilizing agents recited in instant claim 19, a preservative recited in instant claim 20, and 100 mM of phosphate buffered saline (PBS), recited in claim 22.
Starzl teach combining mannitol and sorbitol in paragraph [0415], 2-phenoxyethanol (preservative) in claim 62 and PBS in paragraph [0405] at 100 mM in paragraph [0409].
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have included the pharmaceutical carriers of Starzl in the SARS-CoV-2 formulation of Chen et al. and Gao et al. with a reasonable expectation of success because Starzl teach that the vaccine composition encompasses an inactivated SARS-CoV-2 in paragraphs [0037, 0054, and 0293].
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., Gao et al., and Starzl as applied to claims 1-13, 16-20, 22, and 24-27 above, and further in view of Sumathy et al. (USPgPub 2017/0014502).
See the teachings of Chen et al., Gao et al., and Starzl above.
Starzl teach the inclusion of 2-phenoxyethanol (preservative) in claim 62, but does not teach the concentration recited in instant claim 21.
Sumathy et al. teach the inclusion of 2-phenoxyethanol at a concentration of 2.5 to 5 mg/mL, as recited.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have included the art-recognized concentration of 2-phenoxyethanol in the vaccine formulation of Chen et al., Gao et al., and Starzl with a reasonable expectation of success.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., Gao et al., and Starzl as applied to claims 1-13, 16-20, 22, and 24-27 above, and further in view of Darnell et al. (Journal of Virological Methods. 2004; 121: 85-91).
None of the references teach or suggest storing the inactivated virus at -70°C, as required in claim 23.
Darnell et al. teach storage of clarified SARS at −70◦C in section 2.1.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have stored the SARS-CoV-2 of Chen et al., Gao et al., and Starzl at −70◦C, as taught by Darnell et al. because the SARS-CoV-2 of Chen et al., Gao et al., and Starzl is a SARS virus and Chen et al., Gao et al., Starzl, and Darnell culture the virus in Vero cells prior to inactivation, see “Virus and cells” and “Inactivated vaccine” of Chen et al.; claims 1, 2, 12, 13, 25, and 41 of Gao et al.; paragraphs [0037, 0054, and 0293] of Starzl; and sections 2.3-2.8 of Darnell et al.
Conclusion
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/Shanon A. Foley/Primary Examiner, Art Unit 1671