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 .
Election/Restrictions
Applicant's reply to the Restriction Requirement, dated October 20, 2025, has been received. By way of this reply, Applicant has cancelled claims 23 and 25-27, introduced new claims 29-32, and elected Group I: claims 1-9, 11-12, 17-20, and 24, and the species of a mammalian cell, an internal TATA box, SEQ ID NO.: 7, and Hepatitis B surface antigen.
Applicant’s election in the reply filed on October 20, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-9, 11-12, 17-20, 24, and 29-32 are therefore under examination before the Office.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on at least page 9. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 12 is objected to because of the following informalities: the period at the end of clause (b) should be a semicolon. Appropriate correction is required.
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 20 and 32 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
"[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., 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 takes 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.
Lastly, 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.")
In Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010), it is noted that to show invention, a patentee must convey in its disclosure that is "had possession of the claimed subject matter as of the filing date. Demonstrating possession "requires a precise definition" of the invention. To provide this precise definition" for a claim to a genus, a patentee must disclose "a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus" (see Amgen at page 1358).
Also, it is not enough for the specification to show how to make and use the invention, i.e., to enable it (see Amgen at page 1361).
An adequate written description must contain enough information about the actual makeup of the claimed products – "a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials", which may be present in "functional terminology when the art has established a correlation between structure and function" (Amgen page 1361).
On 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guide lines for claims drawn to antibodies, which can be found at www.uspto.gov/sltes/default/files/docurrienfcs/amgenJ22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen.
In the instant case, claim 20 recites an antibody, or antigen binding fragment thereof, that specifically binds to a 2091-nCOV spike protein antigen. However, as of the effective filing date of February 17, 2020, no such antibody was known to exist. Florindo (Nat Nanotechnol. 2020 Aug;15(8):630-645) states that the first antibody against SARS-CoV-2, LY-CoV555, began clinical trials on June 2, 2020 (page 630, right column, second paragraph). There is no other record of any known antibody against SARS-CoV-2 prior to this date.
Applicant's specification does not describe the characteristics of such an antibody, beyond its ability to bind its cognate antigen. The specification does not disclose any details as to the composition of such an antibody. Applicant's specification does not describe any exemplary such antibody. The disclosure fails to disclose a representative number of species falling with the scope of the genus or structure common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus of the claimed antibody.
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).
Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. 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 takes into account the state of the art at the time of the invention.
Here, the claims are directed to a genus of antigen-binding immunoglobulin molecules are defined by their desired binding to an antigen and function of such binding.
It is well-known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope. For example, Lloyd et al. taught that over hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Protein Eng Des Sel. 2009 Mar;22(3):159-68; see page 159, right column, first paragraph: "Selection of such libraries to a given antigen can give rise to several hundreds to thousands of different antibodies.") The high degree of polymorphism in antibody generation evidences a lack of structure-function correlation for antibodies.
Given the well-known high level of polymorphism of immunoglobulins / antibodies, the skilled artisan would not have been in possession of the vast repertoire of antibodies encompassed by the claimed invention; one of skill in the art would conclude that applicant was not in possession of the structural attributes of a representative number of species possessed by the members of the genera of antibody that binds a 2091-nCOV spike protein antigen broadly encompassed by the claimed invention. One of skill in the art would conclude that the specification fails to disclose a representative number of species to describe the claimed genera.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 5-9, 11-12, 17-18, 24, 29-30 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Rauch (U.S. patent 11,241,493)
Rauch teaches a nucleic acid (i.e., a polynucleotide) comprising at least one coding sequence encoding at least one antigenic peptide or protein derived from a coronavirus SARS-CoV-2 (i.e., nCOV-2019) (col. 2, lines 38-49). Rauch further teaches that the antigen may be the spike protein (col. 4, lines 14-40).
Rauch also teaches that the spike protein has a sequence of SEQ ID NO.: 1 (col. 19, lines 25-35), which is identical to Applicant's SEQ ID NO.: 1.
Rauch further teaches modification of codons of the sequence for expression in a human cell (col. 43, lines 29-31 and col. 44, lines 45-54), which is pertinent to claims 2 and 29.
Rauch further teaches a codon adaptation index (CAI) of at least 0.5, at least 0.8, at least 0.9, or at least 0.95 (col. 46, lines 18-33), which is pertinent to claim 5.
Rauch further teaches a modified coding sequence of SEQ ID NO: 25901 (col. 48, lines 7-26) that is greater than 90% identical to Applicant's SEQ ID NO: 7, which is pertinent to claim 6.
Rauch further teaches that administration of a nucleic acid encoding a spike protein elicits neutralizing antibodies (col. 24, lines 50-58), which is pertinent to claim 7.
Rauch further teaches viral expression vectors comprising the above sequence operably linked to a promoter (col. 57, lines 24-36), which is pertinent to claims 8 and 11.
Rauch further teaches vaccine compositions of the above (col. 10, lines 1-3), which is pertinent to claims 9 and 24.
Rauch further teaches that the spike protein may further comprise a signal peptide (col. 30, lines 47-53), which is pertinent to claim 12.
Rauch further teaches that the spike protein may comprise a receptor binding domain (col. 22, lines 50-59), which is pertinent to claim 17.
Rauch further teaches that above construct may also comprise a Hepatitis B surface antigen (col. 31, lines 35-44), which is pertinent to claim 18.
Rauch further teaches virus-like particle (VLP) forming sequences (col. 30, lines 54-58 and column 34).
Rauch further teaches a receptor-binding domain of SEQ ID NO.: 13243 (col. 19, lines 48-65) that is greater than 90% identical to Applicant's SEQ ID NO.: 15, which is pertinent to claims 9, 11, 17, 30, and 31.
Claims 1, 3, 7-9, 11-12, 17-19, 24 and 31 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Metkar (US20210228707A1).
Metkar teaches a polynucleotide that encodes a coronavirus antigen that comprises an amino acid sequence of SEQ ID NO: 29 and is capable of inducing an immune response, such as a neutralizing antibody response, (para. 0006), which is identical to Applicant's SEQ ID NO.: 1, which is pertinent to claims 1 and 7.
Metkar further teaches codon optimization of the above nucleotide (para. 0019 and 0074-76).
Metkar further teaches that codon optimization may reduce eliminate problem secondary structures within the polynucleotide (para. 0074), which is pertinent to claim 3.
Metkar further teaches that the above polynucleotide may include a promoter (para. 0060), which is pertinent to claim 8.
Metkar further teaches RNA vaccine compositions of the above polynucleotide (para. 0294), which is pertinent to claims 9, 11 and 24.
Metkar further teaches that the above polynucleotide may also comprise a signal peptide (para. 0062), which is pertinent to claim 12.
Metkar further teaches that the above polynucleotide may also encode a fusion protein (para. 0065), which is pertinent to claim 17.
Metkar further teaches that the above polynucleotide may also include a hepatitis B surface antigen for the purpose of forming a virus-like particle (para. 0067), which is pertinent to claims 18-19 and 31.
Claims 1-2, 4, 7-9, 11-12, 20, and 31 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Langedijk (U.S. patent 11,498,944).
Langedijk teaches an isolated nucleic acid molecule comprising a nucleotide sequence that encodes a 2019-nCOV Spike (S) protein (col. 2, lines 58-61), which is identical to Applicant's SEQ ID NO.: 1. Langedijk further teaches optimized nucleic acid molecules (col. 4, lines 24-29 and col. 37, line 58 through col. 38, line 32).
Langedijk further teaches that the polynucleotide is codon optimized for expression in human cells (col. 84, lines 15-17), which is pertinent to claims 2 and 29.
Langedijk further teaches that the polynucleotide may be engineered to include a suitable retroviral vector to stably integrate the polynucleotide into the host genome (col. 64, lines 46-49), which is pertinent to claims 4 and 8.
Langedijk further teaches that the polypeptide may comprise the 2019-nCoV receptor binding domain (col. 61, lines 29-39), which is pertinent to claim 7.
Langedijk further teaches vaccines of the above polynucleotide (col. 3, lines 57-59), which is pertinent to claim 9.
Langedijk further teaches that the above polynucleotide may encode a signal peptide (col. 46, lines 40-52), which is pertinent to claim 12.
Langedijk further teaches antibodies that bind to spike proteins encoded by the above polynucleotide, which may be an Fv, Fab, Fab′-SH, F(ab′)2, a diabody, a linear antibody, or a scFv (col. 5, lines 32-40 and col. 64, line 59 through col. 66, line 15), which is pertinent to claims 20 and 32.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Rauch as applied to claim 1 above, and further in view of Gallei (US20180080044A1).
The teachings of Rauch have been discussed supra. However, Rauch does not teach deletion of a TATA box.
Gallei teaches nucleic acid vaccines against a virus (e.g., para. 0216).
Gallei further teaches the nucleic acid used may be modified to improve functions, such as by codon optimization or removal of cis-acting sites (i.e., motifs) such as (cryptic) splice donor, acceptor sites and branch points, polyadenylation signals, TATA-boxes, chi-sites, ribosomal entry sites, repeat sequences, secondary structures, etc. (para. 0237).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Rauch and Gallei to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Rauch and Gallei are concerned with nucleic acid vaccines against viruses and modifications to such. As Rauch teaches, polynucleotide encoding a spike protein from nCOV-2019 were known in the art, as were methods of optimization. Gallei teaches various other types of optimizations for such sequences, including removes of TATA boxes. One of ordinary skill could apply the optimization techniques of Gallei to the polynucleotide of Rauch by known methods, with each component of the combination performing its known, usual function, and the combination would yield nothing more than predictable results.
Conclusion
No claim is allowed.
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/PETER JOHANSEN/Examiner, Art Unit 1644