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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/16/2025 has been entered.
Claim Status
Claim(s) 1-344, 357 and 362 were canceled.
Claim 366 was added.
Claims 345-356, 358-361 and 363-366 are pending and under consideration.
Claim Objections
Claims 360-361 and 366 are objected to because of the following informalities: “treated water, the treated water is treated with three or more water treatment systems” should read “treated water, wherein the treated water is treated with three or more water treatment systems” for better clarity. Appropriate correction is required.
Claim 361 is objected to because of the following informalities: there must be a period at the end. Appropriate correction is required.
MAINTAINED - Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 345-356, 358-361 and 363-366 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a “written description” rejection.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Regents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., binding to antigen, high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus take into account the state of the art at the time of the invention. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor, 97 USPQ2d at 1875 (“[T]he application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. However, the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims.”). A chimeric antibody shares the full heavy and light chain variable regions with the corresponding mouse antibody; that is, the structure shared between a mouse and chimeric antibody would generally be expected to conserve the antigen binding activity.
Even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
Additionally, “An adequate written description must contain enough information about the actual makeup of the claimed products—“a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials,” which may be present in “functional” terminology “when the art has established a correlation between structure and function.” Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies.” Amgen Inc v. Sanofi 124 USPQ2d 1354, 1361 (Fed. Cir. 2017). “Further, the “newly characterized antigen” test flouts basic legal principles of the written description requirement. Section 112 requires a “written description of the invention.” But this test allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen. The test thus contradicts the statutory “quid pro quo” of the patent system where “one describes an invention, and, if the law's other requirements are met, one obtains a patent.” Ariad, 598 F.3d at 1345.” Amgen at 1362.
Claim Analysis
Instant claims are drawn to an injectable vaccine composition comprising: a purified recombinant protein derived from pupal ovarian cells of Spodoptera frugiperda; hydrochloric acid; sodium hydroxide; a tonicity agent; and polysorbate 80; wherein the pupal ovarian cells are infected with a recombinant baculovirus to produce a recombinant protein, the recombinant protein is purified to produce the purified recombinant protein; the tonicity agent comprises two or more tonicity agents selected from the group consisting of dextrose, glycerol, mannitol, potassium chloride, and sodium chloride.
Instant specification did not disclose any vaccine composition comprising purified recombinant protein, hydrochloric acid, sodium hydroxide, a tonicity agent and polysorbate 80. Instant claims encompass any vaccine composition comprising any type of recombinant protein because instant claims do not define the structure of the recombinant protein (i.e. amino acid sequence). Since instant specification did not disclose a single species of vaccine composition, it does not provide adequate written description for the broadly claimed genus encompassing any recombinant protein as claimed by instant claims. Instant specification did not provide any experimental evidence for the following questions: how was the gene for the recombinant protein cloned?; was the gene verified by sequencing after cloning?; how was the recombinant baculovirus constructed?; how was insect cell infected?; how was insect cell maintained and grown to express the recombinant protein?; how was the recombinant protein purified?; how did the chromatogram look like for the chromatography for the purification of the protein?; did SDS-PAGE gel show any contaminant protein?; was the purified protein identified by mass spectrometry to confirm the correct identity of the protein-of-interest? (i.e. did mass spectrometry give a correct molecular weight?); did the purified protein provide immunity to coronavirus disease as claimed by instant claim 361?; and what is the amino acid sequence for the recombinant protein? Without any experimental evidence disclosed by instant specification, one of ordinary skill in the art would not recognize that applicants were in possession of a single species of vaccine composition, let alone a broad genus encompassing any type of recombinant protein as claimed by instant claims.
The disclosure therefore does not show that applicant was in possession of the necessary common attributes or features possessed by the members of the claimed genus. Accordingly, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
Response to Arguments
In the response filed on 9/16/2025, Applicant argued at page 1 as follows.
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Applicant's arguments have been fully considered but they are not persuasive. Figure 14G shows one non-limiting embodiment of a biocatalyst mixing module that is configured to mix insects, water, biocatalyst, and optionally acid to create an insect liquid biocatalyst mixture (instant specification, page 12). Because instant claims claim vaccine composition, not biocatalyst mixing module, Applicant’s argument is not relevant to instant claims.
Applicant argued at page 2,
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Applicant's arguments have been fully considered but they are not persuasive. Instant specification did not show any experimental data to show the possession of the claimed composition. For example, instant specification did not provide chromatogram to show that purification by chromatography was successful. Instant specification did not provide SDS-PAGE electrophoresis gel to show that the expression was successful and purity of the purified protein was high enough for use as vaccine. Since instant specification did not show any experimental data, Applicant’s argument that the application provides a constructive reduction to practice is not persuasive.
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.
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.
Claims 345-352, 355-356, 358-360 and 365-366 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cox (Vaccine 30 (2012) 1759-1766) in view of Jain et al (Advanced Drug Delivery Reviews 93 (2015) 42-55) and Pramanick et al (Pharma Times, vol. 45, No. 3, March 2013, 65-77).
Regarding claim 345-346, 352, 355, 359, and 365, Cox teaches “The baculovirus-insect cell expression system is a well-known tool for the production of complex proteins. The technology is also used for commercial manufacture of various veterinary and human vaccines” (abstract). Cox teaches “The process steps to produce a recombinant protein in insect cells are shown in Fig. 1. As described earlier the protective antigen is inserted into the baculovirus to generate the recombinant virus (“plug and play”) that is amplified in insect cells to generate the Working Virus Bank (WVB). The insect cells are grown in a bioreactor and infected with the WVB that has been expanded in insect cells at a scale that is approximately 100-fold smaller than the protein production bioreactor. Cells are separated from the media using centrifugation and, dependent on the product that is being produced, either the cell paste or the supernatant is further processed. The protein of interest is solubilized (when applicable) and processed using depth filtration. It is then captured using column chromatography and further purified using additional chromatography. Potential further contaminants can be removed, if required, using membrane filtration technology and, finally, the product is brought into its final buffer composition using ultrafiltration. The process steps indicated in italics are routinely used in monoclonal antibody production” (page 1764, left column). Cox teaches “The baculovirus-insect cell expression system, often referred to as BEVS, is well known as a tool for producing complex proteins, and providing rapid access to biologically active proteins. This protein production platform has been extensively explored for the production of viral and parasitic antigens and, more recently, vaccines have been commercialized demonstrating its potential as a commercial manufacturing technology. … The baculovirus particles or virions contain a large double-stranded DNA genome that on average, depending on the virus species, is 130 kb pairs in size. It can be easily characterized, genetically manipulated and propagated in cell lines derived from a.o. the fall armyworm Spodoptera frugiperda (SF) or the cabbage looper Trichoplusia ni (T. ni), both of which grow well in suspension cultures” (page 1761, left column). It is well known in the art that commercially available commonly used Sf9 and Sf21 insect cell lines are developed from ovarian cells of Spodoptera frugiperda (SF). Cox teaches recombinant “protective antigen” and infectious disease for which the vaccine is used (Table 3, page 1763).
Regarding claims 347-348, Cox teaches “Ion exchange (IEX) columns” and “hydrophobic interaction chromatography (HIC) column” (Figure 1; reproduced below). These chromatography techniques are well known in the art of protein purification.
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Regarding claim 349, gel filtration chromatography is obvious to one of ordinary skill in the art because chromatography columns such as Ni-affinity column, Co-affinity column, ion exchange column, hydrophobic column, and gel filtration column (also known as “size exclusion column”) are well known in the art and also commonly employed in the protein purification art. Skilled artisan usually test these columns to see whether protein-of-interest bind to these columns and therefore these techniques are routine experimentation to one of ordinary skill in the art. Furthermore, instant claim 349 corresponds to product-by-process claim because instant claim 349 claims product (i.e. composition), not process. The wherein-clause of instant claim 349 corresponds to process in product-by-process claim. As long as the product of reference teaches same product, the claimed product is taught by the product of reference because the process of instant claim does not change the structure (i.e. amino acid sequence of the protein) of the claimed product.
Regarding claim 350, instant claims recite commonly used purification techniques which are well known in the art. Therefore, claim 350 is also obvious to one of ordinary skill in the art. Furthermore, as discussed above, claim 350 also corresponds to product-by-process claim.
Regarding claim 351, skilled artisan in the art of protein purification routinely freezes expression host cells in liquid nitrogen and store it at -70C deep freezer before purification and thaw it just before starting purification steps. Therefore, claim 351 recites about the process of purification which is obvious to one of ordinary skill in the art. Furthermore, as discussed above, the process of purification does not change the structure of the claimed product.
Regarding claim 356, reverse phase chromatography is routinely utilized in protein purification art and obvious to one of ordinary skill in the art. Furthermore, as discussed above, the process of purification does not change the structure of the claimed product in the product-by-process claim.
Regarding claim 358, as discussed above, the recombinant protein antigens taught by Cox does not comprise mRNA. There is no evidence to the contrary.
Regarding claims 360 and 366, pharmaceutical composition comprising proteins are formulated in treated water, and therefore claim 366 is obvious to one of ordinary skill in the art. The claim limitation “the treated water is treated with three or more water treatment systems selected from the group consisting of an absorber, an adsorber, an anion, a cation, a distillation system, an ion exchange resin, a membrane, a microwave unit, an ozone unit, and an ultraviolet unit” corresponds to the process of “product-by-process claim” and does not change the structure or substance of the claimed product (i.e. the treated water in this case).
The difference between prior art and the instant invention is that Cox does not teach buffer composition for storage of vaccine comprising NaCl, a tonicity agent and polysorbate 80.
Regarding claim 345, Jain teaches “optimized formulation contained 0.32 M NaCl, 0.01% polysorbate 80, and 10 mM l-histidine (pH 6.2) and maintained 100% potency after 12 months at 4 °C” (page 44, right column). One of ordinary skill in the art would understand that mixture of hydrochloric acid and sodium hydroxide recited by instant claim 345 will produce NaCl solution (HCl + NaOH -> H2O + NaCl). Jain teaches “Excipients such as chitosan glutamate, sucrose, trehalose, sorbitol and mannitol prevented aggregation” (page 49, left column). Therefore, Jain teaches formulation comprising NaCl, polysorbate 80 and mannitol stabilizes the vaccine composition.
Additional reference Pramanick also teaches “Excipients are the integral part of pharmaceutical products development to achieve desired product profile (stability and efficacy)” (abstract). Pramanick teaches “Parenteral formulations should be isotonic with human plasma so as to avoid damage to the tissues. However, not all drugs at their recommended dosage are isotonic with blood, thus requiring the addition of a tonicity adjusting agent to the formulation. The most commonly used tonicity agent is dextrose, while others, such as glycerol and sodium chloride are less commonly used. Other commonly used tonicity adjusting agents are: Glycerin and Mannitol” (page 69, left column). Pramanick teaches “Lecithin, Polysorbate 20, Polysorbate 80, Pluronic F-68, Sorbitan trioleate (span 85) are used, as surfactants in injectable suspensions” (page 72, right column). Therefore, Pramanick teaches that polysorbate 80, NaCl, dextrose, glycerol, and mannitol are used as excipients to pharmaceutical compositions.
It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have included NaCl, polysorbate 80, dextrose, glycerol and mannitol as excipients to the vaccine composition because prior art teaches that these excipients help stabilize vaccine compositions. Adding these excipients into the composition and testing the stability of the composition is routine experimentation well known in the art. Finding optimal buffer condition for the given protein is within routine skill of the skilled artisan in the art. Therefore, the invention as a whole would have been obvious to one of ordinary skill in the art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because prior art teaches that excipients such as NaCl, polysorbate 80, dextrose, glycerol and mannitol help stabilize vaccine compositions. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 345-356, 358-361 and 363-366 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cox (Vaccine 30 (2012) 1759-1766) in view of Jain et al (Advanced Drug Delivery Reviews 93 (2015) 42-55) and Pramanick et al (Pharma Times, vol. 45, No. 3, March 2013, 65-77) as applied to claims 345-352, 355-356, 358-360, and 365-366 above, and further in view of Wrapp et al (Science 367, 1260-1263 (2020)).
Instant application claims domestic benefit on parent case 15/242,579 (filed 8/21/2016). However, parent case 15/242,579 does not support vaccine composition that provides immunity to coronavirus disease as claimed by instant claims 353-354 and 361-364, and therefore EFD of instant claims 353-354 and 361-364 is the filing date of instant application (3/18/2020).
Wrapp et al was published online on 02/19/2020 (see at the end of cited reference) and therefore available as 102(a)(1) art.
Regarding claims 345-352, 355-356, 358-360, and 365-366, teachings of Cox, Jain and Pramanick were discussed above.
However, Cox, Jain and Pramanick do not teach vaccine that provide immunity to coronavirus disease.
Regarding claims 353-354, 361 and 363-364, Wrapp teaches cryo-EM structure of the 2019-nCoV spike protein. 2019-nCoV is an alternative name of SARS-CoV-2. Wrapp teaches that the CoV spike (S) glycoprotein is a key target for vaccines (abstract).
It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to have applied insect cell vaccine protein expression system taught by Cox, Jain and Pramanick to express CoV spike (S) glycoprotein because Wrapp teaches that the CoV spike (S) glycoprotein is a key target for vaccines (abstract). Since insect cell vaccine expression system was well known in the art and coronavirus pandemic required a new vaccine for coronavirus disease, one of ordinary skill in the art would be motivated to apply insect cell expression system to produce vaccine for coronavirus disease. Therefore, the invention as a whole would have been obvious to one of ordinary skill in the art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because prior art teaches that insect cell expression system for vaccine production was effective in production of vaccine. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
In the response filed on 9/16/2025, Applicant argued at page 4,
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Applicant's arguments have been fully considered but they are not persuasive. Because insect expression system is well known in the art, one of ordinary skill in the art would be motivated to use this system to express recombinant protein to use as a vaccine. Furthermore, one of ordinary skill in the art would have included NaCl, polysorbate 80, dextrose, glycerol and mannitol as excipients to the vaccine composition because prior art teaches that these excipients help stabilize vaccine compositions. Adding these excipients into the composition and testing the stability of the composition is routine experimentation well known in the art. Finding optimal buffer condition for the given protein is within routine skill of the skilled artisan in the art.
Applicant argued at page 5,
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Applicant's arguments have been fully considered but they are not persuasive. One of ordinary skill in the art would not have had 100% certainty in expectation of success. If one of ordinary skill in the art would have had a reasonable expectation of success, then the claimed invention would be obvious. Adding excipients into the protein composition and testing the stability of the composition is routine experimentation well known in the art. Finding optimal buffer condition for the given protein is within routine skill of the skilled artisan in the art.
Applicant argued at page 5,
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Applicant's arguments have been fully considered but they are not persuasive. While Nuvaxovid comprises specific protein from SARS-CoV-2 virus, instant claims encompass any and all types of recombinant proteins because instant claims do not recite specific protein. Therefore, just because same buffer condition stabilizes Nuvaxovid does not mean that the same buffer condition can stabilize any and all types of proteins as claimed by instant claims. Furthermore, instant specification does not provide any experimental evidence about stability of the buffer condition recited by instant claims. Therefore, Applicant’s argument is not persuasive.
Applicant argued at page 5,
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Applicant's arguments have been fully considered but they are not persuasive. As discussed above, instant claims encompass any and all types of proteins and Nuvaxovid comprises specific protein from SARS-CoV-2. Therefore, Applicant’s argument about Nuvaxovid is not relevant to instant claims.
Conclusion
No claim is allowed.
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/CHEOM-GIL CHEONG/
Examiner, Art Unit 1645
/GARY B NICKOL/Supervisory Patent Examiner, Art Unit 1645