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 .
Claims Status
The amendments of 06//24/2025 have been entered.
Claims 2-3 and 5 are cancelled. All rejections of claims 2-3 and 5 are moot in light of applicant’s cancellation of claims 2-3 and 5.
Claims 1, 4, and 6-14 are pending and being examined.
All previous objections and rejections not set forth below have been withdrawn in view
of applicant’s amendments to the claims.
Claim Interpretation
Claim 13 recites “culturing the transgenic organism”. The Applicant does not define or describe what is meant by “culturing”. The examiner interprets the word “culture” (verb) to mean “cultivate”, as per Merriam Webster dictionary. Thus, “culturing” is interpreted as to growing or cultivating organisms including plants.
Claim 13 recites “pulverizing”. The examiner interprets the word “pulverizing” to mean “to reduce (as by crushing, beating, or grinding) to very small particles”, as per Merriam Webster dictionary.
Response to Amendments
Inventor's Declaration, by Dr. Hwan Hwang, filed under 37 CFR 1.132 on 6/24/2025, is fully considered in the Final Office action. However, the arguments were not found persuasive, as described below.
Claim Rejections - 35 USC § 102
Response to Applicants’ arguments: Amendments made to the claims filed in Applicant’s response submitted on 06/24/2025 overcame the rejection of record.
Claim Rejections - 35 USC § 103
Claims 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (W) (Immunogenicity and Protection Efficacy of Monomeric and Trimeric Recombinant SARS Coronavirus Spike Protein Subunit Vaccine Candidates, 2013, Viral Immunology, 26:126–132), in view of BoseDasgupta et al. (Coronin 1 trimerization is essential to protect pathogenic mycobacteria within macrophages from lysosomal delivery, 2014, FEBS Letters 588:3898–3905). Due to Applicant’s amendments, the rejection is modified from the rejection set forth on pages 3-17 in the Office action dated 3/24/2025.
Claim 1 is drawn to a recombinant vector for producing a recombinant spike protein of a coronavirus belonging to any one of SARS-CoV (SARS-Coronavirus), MERS-CoV (MERS-Coronavirus) or SARS-CoV-2 (SARS-Coronavirus-2) group; forming a trimer, comprising: (i) a gene encoding a protein lacking an amino acid sequence from the transmembrane domain to the C-terminus of the spike protein of a coronavirus; a protein including an amino acid sequence from the N-terminus to sub- domain 2 (SD 2) of the spike protein of a coronavirus; or a protein lacking an amino acid sequence from the transmembrane domain in subunit 2 to the C-terminus of the spike protein of a coronavirus; and (ii) a gene encoding a protein of a trimeric motif region of Coronin1.
Li et al. (W) teaches recombinant vectors, using a baculovirus vector backbone, (page 127, left column, first para) comprising nucleotide encoding the trimerized forms of the S1 domain (a.a. 14–667) or the S2 domain (a.a. 668–1192) of the spike protein of a SARS-CoV coronavirus cloned in the vector (page 127, left column, para 2). Trimerization of the cloned proteins is achieved by using bacteriophage T4 foldon domain (page 126, abstract; right column, para 1). It teaches about transgenic insect (SF9) cells expressing the recombinant vector (page 127, left column, para 3). Li et al. (W) also teaches that recombinant spike proteins based on either the S1 domain or the full-length ectodomain of S protein are suitable vaccine candidates. The recombinant protein comprising the S1 domain, described by Li et al., lacks the amino acid sequence from the transmembrane domain in subunit 2 to the C-terminus of the spike protein of a coronavirus comprising an amino acid sequence of instant SEQ ID NO: 6 comprising 682nd amino acid to 1213th amino acid in S2 subunit of the spike protein (spec, page 10, line 12-14). Li et al. (W) also suggests that the full-length ectodomain engineered to form a secreted trimer may be a superior form of SARS subunit vaccine, and a secreted protein would likely be easier to produce than the native membrane protein (page 131, left column, para 4). Li et al. also describes that the protein produced by the recombinant vector in the host cells lacks are present in the supernatants of the culture (page 127, left column, para 3, line 3-6) implying that the protein soluble.
However, Li et al. (W) does not teach a gene encoding a protein of a trimeric motif region of Coronin1.
BoseDasgupta et al. teaches Coronin1 proteins which are characterized by the presence of a central WD repeat and a C-terminal coiled coil in coronin1 responsible for trimerization (page 3898, abstract). It also asserts that the role for the C-terminal coiled coil domain or motif of coronin1 trimerization is well established in the art (page 3898, right column, last para).
Before the effective filing date of the invention, it would have been prima facie obvious
to a person of ordinary skill in the art to produce recombinant vectors to express one or more truncated versions of a coronavirus spike protein in trimer forms in a suitable expression system with produce proteins which can be used as potential vaccine against the target coronavirus including SARS-CoV with a realistic goal to produce a superior form of SARS vaccine comprising a secreted protein which is likely to be easier to produce than the native membrane protein, as discussed in Li et al. (W). Before the time of filing this invention, one ordinarily skilled in the art would have been motived to clone nucleotide sequences encoding a spike protein lacking an amino acid sequence from the transmembrane domain to the C-terminus of the spike protein of a coronavirus; or a (S1) protein including an amino acid sequence from the N-terminus to S2 or sub- domain 2 (SD 2) of the spike protein of a coronavirus; or a (S2) protein lacking an amino acid sequence from the transmembrane domain in subunit 2 to the C-terminus of the spike protein of a coronavirus including SARS-CoV to produce a transgenic organism by transforming a eukaryotic organism as taught by Li et al (U), while using a the trimeric of trimerization motif from Coronin1 as taught by BoseDasgupta et al. Different trimeric or trimerization motifs including Coronin1 and Foldon, are functional equivalents. Replacing Foldon motif with the coronin1 motif is a simple substitution of one known element for another, with predictable results to produce a superior form of SARS subunit vaccine, and a secreted protein which is likely to be easier to produce than the native membrane protein.
Regarding claim 4, Li et al. (W) describes a recombinant vector comprising nucleotide sequence encoding the S1 domain (a.a. 14–667) (page 2, left column, para 3, line 17), which lacks the amino acid sequence from the transmembrane domain to the C-terminus of the spike protein of SARS-CoV-2.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (W) (Immunogenicity and Protection Efficacy of Monomeric and Trimeric Recombinant SARS Coronavirus Spike Protein Subunit Vaccine Candidates, 2013, Viral Immunology, 26:126–132) and BoseDasgupta et al. (Coronin 1 trimerization is essential to protect pathogenic mycobacteria within macrophages from lysosomal delivery, 2014, FEBS Letters 588:3898–3905) as applied to claims 1 and 4 above, and further in view of Capobianchi et al. (Molecular characterization of SARS-CoV-2 from the first case of COVID-19 in Italy, 2020, Clin. Microbiol. Infect., 26:954–956; Published online on March 27, 2020).
Claim 6 is drawn to the recombinant vector of claim 1, wherein the gene encoding the protein comprising an amino acid sequence from the N-terminus to sub-domain 2 (SD 2) of the spike protein of SARS-CoV-2 comprises the nucleotide sequence of SEQ ID NO: 3.
Li et al.(U) teaches recombinant vectors comprising nucleotide sequences encoding trimerized forms of the S1 domain (a.a. 14–667) or the S2 domain (a.a. 668–1192) of the spike protein of a SARS-CoV coronavirus cloned in the baculovirus vector backbone (page 127, left column, para 2). It also teaches that the full-length ectodomain engineered to form a secreted trimer may be a superior form of SARS subunit vaccine, and a secreted protein would likely be easier to produce than the native membrane protein (page 131, left column, para 4). BoseDasgupta et al. teaches use of the trimerization domain/motif of Coronin1 protein, which is characterized by the presence of a central WD repeat and a C-terminal coiled coil in coronin1. The trimerization domain of Coronin1 is used for trimerization of an otherwise monomeric protein is well established in the art (BoseDasgupta et al., page 3898, right column, last para).
However, they do not teach SEQ ID NO: 3.
Capobianchi et al. teaches amino acid subsequences having 100% homology with SEQ SEQ ID NO: 4, as shown below.
RESULT 11
A0A679G9E9_SARS2
RC STRAIN=SARS-CoV-2/human/ITA/INMI1/2020 {ECO:0000313|EMBL:QIC50498.1};
RX PubMed=32229288;
RA Capobianchi M.R., Rueca M., Messina F., Giombini E., Carletti F.,
RA Colavita F., Castilletti C., Lalle E., Bordi L., Vairo F., Nicastri E.,
RA Ippolito G., Maria Gruber C.E., Bartolini B.;
RT "Molecular characterization of SARS-CoV-2 from the first case of COVID-19
RT in Italy.";
RL Clin. Microbiol. Infect. 26:954-956(2020).
RN [5] {ECO:0000313|EMBL:QIK02132.1
Query Match 100.0%; Score 3575; Length 1273; Best Local Similarity 100.0%;
Matches 666; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNG 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 16 VNLTTRTQLPPAYTNSFTRGVYYPDKVFRSSVLHSTQDLFLPFFSNVTWFHAIHVSGTNG 75
Qy 61 TKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQF 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 76 TKRFDNPVLPFNDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQF 135
Qy 121 CNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFK 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 136 CNDPFLGVYYHKNNKSWMESEFRVYSSANNCTFEYVSQPFLMDLEGKQGNFKNLREFVFK 195
Qy 181 NIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 196 NIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTPGDSS 255
Qy 241 SGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 256 SGWTAGAAAYYVGYLQPRTFLLKYNENGTITDAVDCALDPLSETKCTLKSFTVEKGIYQT 315
Qy 301 SNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 316 SNFRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFS 375
Qy 361 TFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIA 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 376 TFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIA 435
Qy 421 WNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSY 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 436 WNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSY 495
Qy 481 GFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTES 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 496 GFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNFNFNGLTGTGVLTES 555
Qy 541 NKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDV 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 556 NKKFLPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVITPGTNTSNQVAVLYQDV 615
Qy 601 NCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQ 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 616 NCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQ 675
Qy 661 TQTNSP 666
||||||
Db 676 TQTNSP 681
The nucleotide sequence comprising SEQ ID NO: 3 (of instant claim 6) translates into amino acid sequence comprising SEQ ID NO: 4. A skilled artisan would acknowledge that any nucleotide sequence encoding a polypeptide consisting of SEQ ID NO: 4 would be identical and/or similar in terms of protein structure and function as implied in claim 6.
Before the effective filing date, it would have been obvious to a person with ordinary skill in the art to develop recombinant vectors to clone nucleotide sequences encoding a spike protein of a coronavirus including SARS-CoV-2 lacking an amino acid sequence from the transmembrane domain to the C-terminus of the spike protein; or a (S1) protein including an amino acid sequence from the N-terminus to S2 or sub- domain 2 (SD 2) of the spike protein of a coronavirus; or a (S2) protein lacking an amino acid sequence from the transmembrane domain in subunit 2 to the C-terminus of the spike protein of a coronavirus to produce a transgenic organism by transforming an eukaryotic organism as described by Li et al (U), while using a the trimeric of trimerization motif from Coronin1 as described by BoseDasgupta et al., as described before. Any specific nucleotide sequences (as the one described by Capobianchi et al.) encoding a spike protein comprising 100% identity to SEQ ID NO 4 is a functional equivalent. It is within the experimental design choice of an ordinarily skilled artisan to use any specific nucleotide sequences encoding a spike protein comprising 100% identity to SEQ ID NO 4 to produce a superior form of SARS vaccine comprising a secreted protein which is likely to be easier to produce than the native membrane protein without expecting any surprising or unexpected result.
Before the effective filing date of the invention, an ordinarily skilled artisan would have been motivated to produce recombinant vectors to express one or more truncated versions of a coronavirus spike protein(s) in trimeric forms using a nucleotide sequence encoding a protein comprising 100% sequence identity to SEQ ID NO: 4, with a realistic goal to produce a recombinant spike protein which can be used as potential vaccine against the a coronavirus including SARS-CoV-2.
Claims 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (W) (Immunogenicity and Protection Efficacy of Monomeric and Trimeric Recombinant SARS Coronavirus Spike Protein Subunit Vaccine Candidates, 2013, Viral Immunology, 26:126–132) and BoseDasgupta et al. (Coronin1 trimerization is essential to protect pathogenic mycobacteria within macrophages from lysosomal delivery, 2014, FEBS Letters 588:3898–3905) as applied to claims 1 and 4 above, and further in view of Kammerer et al. (A conserved trimerization motif controls the topology of short coiled coils, 2005, Proc. Natl. Acad. Sci. U.S.A. 102:13891-13896).
Li et al. (W) teaches recombinant vectors comprising nucleotide sequences encoding trimerized forms of the S1 domain (a.a. 14–667) or the S2 domain (a.a. 668–1192) of the spike protein of a SARS-CoV coronavirus (page 127, left column, para 2). It also teaches that the full-length ectodomain engineered to form a secreted trimer may be a superior form of SARS subunit vaccine, and a secreted protein would likely be easier to produce than the native membrane protein (page 131, left column, para 4). BoseDasgupta et al. teaches use of the trimerization domain/motif of Coronin1 protein, as discussed above.
However, they do not teach a trimeric motif region of Coronin1 comprising instant SEQ ID NO. 7 or SEQ ID NO. 8.
Kammerer et al. teaches a conserved trimerization motif comprising a three-stranded 32 amino acid residue coil-coil domain of Coronin1 protein (page 13891, right column, para 2), which has 100% sequence homology with SEQ ID NO. 8, as shown in he alignment below.
RESULT 8
COR1A_MOUSE
ID COR1A_MOUSE
AC O89053; Q7TMU0; Q9R1Y8; Q9R288; Reviewed; 461 AA.
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 5.
DT 27-NOV-2024, entry version 199.
DE RecName: Full=Coronin-1A;
DE AltName: Full=Coronin-like protein A;
DE Short=Clipin-A;
DE AltName: Full=Coronin-like protein p57;
DE AltName: Full=Tryptophan aspartate-containing coat protein;
GN Name=Coro1a; Synonyms=Coro1;
OS Mus musculus (Mouse).
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.
PubMed=16172398; DOI=10.1073/pnas.0502390102;
RA Kammerer R.A., Kostrewa D., Progias P., Honnappa S., Avila D., Lustig A., Winkler F.K., Pieters J., Steinmetz M.O.;
RT "A conserved trimerization motif controls the topology of short coiled coils."
RL Proc. Natl. Acad. Sci. U.S.A. 102:13891-13896(2005).
Query Match 100.0%; Score 151; Length 461; Best Local Similarity 100.0%;
Matches 32; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 VSRLEEDVRNLNAIVQKLQERLDRLEETVQAK 32
||||||||||||||||||||||||||||||||
Db 430 VSRLEEDVRNLNAIVQKLQERLDRLEETVQAK 461
The nucleotide sequence of instant SEQ ID NO. 7 encodes the polypeptide sequence of instant SEQ ID NO. 8 (spec, page 10, line 18-21).
Before the effective filing date, a person with ordinary skill in the art would be motived to develop recombinant vectors to clone nucleotide sequences encoding a spike protein of a coronavirus including SARS-CoV-2 lacking an amino acid sequence from the transmembrane domain to the C-terminus of the spike protein; or a (S1) protein including an amino acid sequence from the N-terminus to S2 or sub- domain 2 (SD 2) of the spike protein of a coronavirus; or a (S2) protein lacking an amino acid sequence from the transmembrane domain in subunit 2 to the C-terminus of the spike protein of a coronavirus to produce a transgenic organism by transforming an eukaryotic organism as taught by Li et al (U), while using a the trimeric or trimerization motif of Coronin1 as taught by BoseDasgupta et al. and Kammerer et al. Use of any specific nucleotide sequence encoding the trimerization motif of Coronin1 protein comprising SEQ ID NO. 8 is within the experimental choice of the Applicant to produce a SARS vaccine comprising a secreted protein which is likely to be easier to produce than the native membrane protein without expecting any surprising or unexpected result.
Before the effective filing date of the invention, it would have been prima facie obvious
to a person of ordinary skill in the art to substitute the nucleotide sequence encoding the trimerization motif of Coronin1 as described by of BoseDasgupta and Kammerer et al. with a functional equivalent comprising SEQ ID NO. 7 encoding a protein consisting of SEQ ID NO. 8 with the realistic goal to produce recombinant spike proteins which can be used as potential vaccine against the target coronavirus including SARS-CoV and SARS-CoV-2.
Claims 9-14 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (W) (Immunogenicity and Protection Efficacy of Monomeric and Trimeric Recombinant SARS Coronavirus Spike Protein Subunit Vaccine Candidates, 2013, Viral Immunology, 26(2):126–132) and BoseDasgupta et al. (Coronin 1 trimerization is essential to protect pathogenic mycobacteria within macrophages from lysosomal delivery, 2014, FEBS Letters 588:3898–3905) as applied to claims 1 and 4 above, and further in view of Li et al. (X) (Accumulation of Recombinant SARS-CoV Spike Protein in Plant Cytosol and Chloroplasts Indicate Potential for Development of Plant-Derived Oral Vaccines, 2006, Experimental biology and medicine, 231:1346–1352).
Claim 9 is drawn to a binary vector while claim 10 is drawn to a binary vector comprising any one promoter selected from the group consisting of a 35S promoter derived from cauliflower mosaic virus, a 19S RNA promoter derived from cauliflower mosaic virus, a Mac promoter, an actin, and a ubiquitin promoter of a plant. Claims 13-14 are drawn to a recombinant protein and the method for producing the recombinant spike protein of a coronavirus forming a trimer in a plant, comprising the steps of: (a) constructing the recombinant vector of claim 1; (b) preparing a transgenic organism by introducing the recombinant vector into an organism; (c) culturing the transgenic organism; (d) infiltrating the culture product into a plant; and (e) pulverizing the plant to obtain a recombinant spike protein of a coronavirus forming a trimer.
As discussed above while rejecting claims 1 and 4; Li et al. (W) describes recombinant vectors comprising nucleotide encoding the trimerized forms of the S1 domain (a.a. 14–667) or the S2 domain (a.a. 668–1192) of the spike protein of a SARS-CoV coronavirus (page 127, left column, para 2). It describes that the full-length ectodomain engineered to form a secreted trimer may be a superior form of SARS subunit vaccine, and a secreted protein would be easier to produce than the native membrane protein (page 131, left column, para 4).
However, they do not teach any binary vector comprising any plant specific promoter used for expressing any cloned nucleotide sequence in a plant. They also do not teach any transgenic plant expressing any recombinant spike protein.
Li et al. (X) teaches expressing SARS-CoV spike protein (S1, amino acids 1-658) in transgenic plants (page 1346, abstract). It uses a binary vector (pCV2) containing a 35S promoter derived from cauliflower mosaic virus for Agrobacterium-mediated transformation to produce transgenic tobacco and lettuce plants (page 1346, abstract; page 1349, right column, last para). It also teaches a method for producing a recombinant spike protein of a coronavirus SARS-CoV in a transgenic plant (as recited in claim 11-12) by introducing the recombinant vector into the plant (page 1348, left column, para 2; page 1348, right column, para 2-3), which is an eukaryote (as recited in claim 12). A person skilled in the art would acknowledge that constructing the recombinant vector; preparing a transgenic organism including transgenic agrobacterium (a prokaryote); culturing the transgenic organism including agrobacteria, introducing the recombinant vector via transgenic agrobacteria into another organism including a plant (an eukaryote) by infiltrating the agrobacterial culture into the plant; and pulverizing (comprising grinding and producing small pieces to isolate contents from plant material) (as recited in claim 13), is standard in the art. Li et al. (X) describes the desirability and feasibility of producing recombinant coronavirus spike protein (S1) (as recited in claim 14) in transformed plants, indicating its potential in development of a plant-derived and safe oral vaccine against the SARS-CoV in edible plants (page 1346, abstract; page 1351, right column, para 2).
Before filing of this invention, it would have been obvious to one ordinarily skilled in the art would be motived to express a recombinant spike protein of a coronavirus including SARS-CoV in a plant to produce safe oral vaccine produced in an edible plant, as taught by Li et al (X). The method would comprise cloning the necessary nucleotide sequence(s) of the spike protein(s) in a vector, as described by Li et al. (W), containing a suitable trimerization motif, as taught by BoseDasgupta et al. (V), and a promoter including 35S CaMV promoter for a suitable binary vector to express in a plant, as taught by Li et al. (X).
Before the effective filing date of this invention, one ordinarily skilled in the art would have been motivated to express a recombinant spike protein of a coronavirus including SARS-CoV in plant with a realistic objective to produce safe oral vaccine produced in an edible plant by cloning the necessary nucleotide sequence(s) of the spike protein(s) linked in-frame to a trimerization motif in a plant expression vector containing a suitable promoter including 35S CaMV promoter.
Response to Applicant’s arguments
The Applicant discussed “unexpected results” (response, page 3, para 3, line 1-2) that enhanced soluble expression while using Coronin 1 (mCor1) protein as compared to weaker soluble expression using foldon domain as described in the prior art Li et al. (W) (response, page 3, para 3, line 3-10, and page 4, para 1, line 1-2). The Applicant is reminded that the none of the claims comprise the “unexpected results” with “enhanced soluble expression” of the trimerized protein(s) using Coronin1 (mCor1). The Applicant alleges that “cited references fail to provide motivation and a reasonable expectation of success to arrive at the claimed oral liquid composition” (response, page 9, para 3).
The Examiner disagrees. All the Office actions describe the rejections under U.S.C. § 103 by establishing prima facie case of obviousness by first establishing relevant prior art and, secondly, why an ordinarily skilled artisan would be motivated to combine different elements of the prior art with a realistic and predictable outcome. Regarding trimerization, different trimeric or trimerization motifs including Coronin1 and Foldon, are functional equivalents. Replacing Foldon motif with the coronin1 motif is an experimental design choice and constitutes a simple substitution of one known element for another with predictable results (See MPEP § 2143) to produce a superior form of SARS subunit vaccine, and a secreted protein which is likely to be easier to produce than the native membrane protein, as described above. The Applicant does not provide any evidence on the contrary. Moreover, Li et al. (W) does not compare Foldon with Coronin1 in the context of antigenicity of the S1 domain of the coronavirus spike protein.
The Applicant alleges that protein with a foldon domain (constructs 4-6), instead of mCor1, resulted in weak soluble expression while proteins with mCor1 resulted in significantly enhanced soluble expression (response, page 11, para 1, line 9-16). However, the Applicant is reminded that the claims do not recite any specific level of weaker or stronger expression of the recombinant proteins.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new grounds of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAY CHATTERJEE whose telephone number is (703)756-1329. The examiner can normally be reached (Mon - Fri) 8.30 am to 5.30 pm..
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Shubo (Joe) Zhou can be reached on 571-272-0724. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Jay Chatterjee
Patent Examiner
Art Unit 1662
/Jay Chatterjee/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Primary Examiner, Art Unit 1663