DETAILED ACTION
Disposition of Claims
Claims 11-21, 23, 25, and 27-31 are pending.
Examiner’s Note
All paragraph numbers (¶) throughout this office action, unless otherwise noted, are from the US PGPub of this application US20240009300A1, Published 01/11/2024.
Applicant is encouraged to utilize the new web-based Automated Interview Request (AIR) tool for submitting interview requests; more information can be found at https://www.uspto.gov/patent/laws-and-regulations/interview-practice.
Of note, there is not an attorney of record on file due to a lack of an official power of attorney of record. While a customer number has been provided on the ADS submitted 05/03/2023, this is not the equivalent of a power of attorney or an authorization to act in a representative capacity. In order to expedite prosecution in the instant application, it is suggested that a power of attorney be filed as per MPEP §402 or MPEP §1807, or an Authorization to Act in a Representative Capacity be filed as per MPEP §403 in order for the Office to freely and openly discuss the merits of the case with the applicant's representative(s). Please refer to https://www.uspto.gov/about-us/contact-us if you have questions regarding the proper filing of a power of attorney.
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Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because of the use of implied phraseology (e.g. “Disclosed herein…” and “Also disclosed herein…”). A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 20 is objected to because of the following informalities: a period should be at the end of the claim. Appropriate correction is required.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim 11 is drawn to a nucleic acid molecule comprising a nucleotide sequence encoding a SARS-CoV-2 spike protein receptor binding domain (RBD), wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence encodes a peptide comprising an amino acid sequence having at least about 90% identity over an entire length of an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8;
(b) the nucleotide sequence encodes a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8;
(c) the nucleotide sequence encodes at least two peptides, wherein each of the at least two peptides comprises an amino acid sequence having at least about 90% identity over an entire length of an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8; and
(d) the nucleotide sequence encodes at least two peptides, wherein each of the at least two peptides comprises an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8.
Further limitations on the nucleic acid molecule of claim 11 are wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence having at least about 90% identity over an entire length of the nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5 and SEQ ID NO:7;
(b) the nucleic acid sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5 and SEQ ID NO:7;
(c) the nucleotide sequence encodes at least two peptides, wherein each of the encoding sequences comprises at least about 90% identity over an entire length of a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5 and SEQ ID NO:7; and
(d) the nucleotide sequence encodes at least two peptides, wherein each of the encoding sequences comprises a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5 and SEQ ID NO:7 (claim 12); wherein the nucleic acid molecule further encodes an oligomerization domain selected from the group consisting of:
(a) a peptide comprising an amino acid sequence having at least about 90% identity over an entire length of an amino acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18 and SEQ ID NO:20; and
(b) a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18 and SEQ ID NO:20 (claim 13), wherein the nucleotide sequence encoding the oligomerization domain is selected from the group consisting of:
(a) a nucleotide sequence having at least about 90% identity over an entire length of a nucleotide sequence selected from the group consisting of SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17 and SEQ ID NO:19; and
(b) a nucleotide sequence selected from the group consisting of SEQ ID NO:11, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17 and SEQ ID NO:19 (claim 14); wherein the nucleotide sequence encodes self-assembling nanoparticle comprising an amino acid sequence selected from the group consisting of:
(a) an amino acid sequence having at least about 90% identity over an entire length of an amino acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66 and SEQ ID NO:68;
(b) an amino acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66 and SEQ ID NO:68; and
(c) a fragment comprising at least 60% of the full length amino acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66 and SEQ ID NO:68 (claim 15), wherein the nucleic acid molecule encoding the self-assembling nanoparticle comprises a nucleotide sequence selected from the group consisting of:
(a) a nucleotide sequence having at least about 90% identity over an entire length of a nucleotide sequence selected from the group consisting of SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65 and SEQ ID NO:67;
(b) a nucleotide sequence selected from the group consisting of SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65 and SEQ ID NO:67; and
(c) a fragment comprising at least 60% of the full length nucleotide sequence selected from the group consisting of SEQ ID NO:21, SEQ ID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:31, SEQ ID NO:33, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:63, SEQ ID NO:65 and SEQ ID NO:67 (claim 16); and wherein the nucleic acid molecule comprises an expression vector (claim 17).
Claim 18 is drawn to a peptide comprising an amino acid sequence selected from the group consisting of: (a) a peptide comprising an amino acid sequence having at least about 90% identity over an entire length of an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8; (b) a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8; (c) an amino acid sequence comprising at least two peptides, wherein each of the at least two peptides comprises an amino acid sequence having at least about 90% identity over an entire length of an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8; and (d) an amino acid sequence comprising at least two peptides, wherein each of the at least two peptides comprises an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6 and SEQ ID NO:8.
Further limitations on the peptide of claim 18 are wherein the peptide is further comprising an oligomerization domain selected from the group consisting of:
(a) a peptide comprising an amino acid sequence having at least about 90% identity over an entire length of an amino acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18 and SEQ ID NO:20; and
(b) a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ ID NO:18 and SEQ ID NO:20 (claim 19); comprising a self-assembling nanoparticle comprising an amino acid sequence selected from the group consisting of:
(a) an amino acid sequence having at least about 90% identity over an entire length of an amino acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66 and SEQ ID NO:68;
(b) an amino acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66 and SEQ ID NO:68; and
(c) a fragment comprising at least 60% of the full length amino acid sequence selected from the group consisting of SEQ ID NO:22, SEQ ID NO:24, SEQ ID NO:26, SEQ ID NO:28, SEQ ID NO:30, SEQ ID NO:32, SEQ ID NO:34, SEQ ID NO:36, SEQ ID NO:38, SEQ ID NO:40, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:46, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:52, SEQ ID NO:54, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:60, SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:66 and SEQ ID NO:68 (claim 19)
Claim 21 is drawn to a method of inducing an immune response against SARS Coronavirus 2 (SARS-CoV-2) in a subject in need thereof, the method comprising administering an immunogenic composition of claim 1, a nucleic acid molecule of claim 11 or a peptide of claim 18 to the subject.
Claim 23 is drawn to a method of protecting a subject in need thereof from infection with SARS-CoV-2, the method comprising administering an immunogenic composition of claim 1, a nucleic acid molecule of claim 11 or a peptide of claim 18 to the subject.
Claim 25 is drawn to a method of treating a subject in need thereof against SARS-CoV-2, the method comprising administering an immunogenic composition of claim 1, a nucleic acid molecule of claim 11 or a peptide of claim 18 to the subject, wherein the subject is thereby resistant to one or more SARS-CoV-2 strains.
Claim 27 is drawn to a method of inducing an immune response against SARS Coronavirus 2 (SARS-CoV-2) in a subject in need thereof, the method comprising administering a peptide of claim 18 to the subject.
Claim 28 is drawn to a method of protecting a subject in need thereof from infection with SARS-CoV-2, the method comprising administering a peptide of claim 18 to the subject.
Claim 29 is drawn to a method of treating a subject in need thereof against SARS-CoV-2, the method comprising administering a peptide of claim 18 to the subject, wherein the subject is thereby resistant to one or more SARS-CoV-2 strains.
An immunogenic composition comprising a nucleic acid molecule of claim 11 (claim 30) or a peptide of claim 18 (claim 31).
Claim Rejections - 35 USC § 112(b); Second Paragraph
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 11 and 18 and dependent claims 12-17, 19-21, 23, 25, and 27-31 thereof 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.
The term “at least about” in claims 11 and 18 and dependent claims thereof is a relative term which renders the claim indefinite. The term “at least about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As the term “at least about” is in reference to a percent identity with respect to a sequence, it is unclear if this is a certain range (e.g. +/- 10%) or specific number of mutations which are tolerated within the sequence. As no specific definition has been provided for in the specification, and there is no specific definition within the art, the metes and bounds of what is being claimed is unclear.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 11 and 18 are rejected on the grounds of being indefinite. Claims 12-17, 19-21, 23, 25, and 27-31 are also rejected since they depend from claim 11 or 18, but do not remedy these deficiencies of claim 11 or 18.
Claim 11 and dependent claims 12-17, 21, 23, 25, and 30 thereof 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.
The term “receptor binding domain” or “RBD” in claim 1 is a relative term which renders the claim indefinite. The term “RBD” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The art varies in where the RBD can be found in SARS CoV-2 spike (S) protein; Lan et. al. teaches the RBD to be considered to be about R319-F541 of the full-length S protein (See e.g. Fig. 1 of Lan J, et. al. Nature. 2020 May;581(7807):215-220. Epub 2020 Mar 30. ), while Smaoui et. al. (Smaoui MR, et. al. Sci Rep. 2021 Apr 28;11(1):9166.) teaches the RBD is between amino acids N331-V524 (Fig. 1, Supp. Table S1). An alignment of SEQ ID NO: 2 with a full-length wild-type SARS CoV-2 S protein sequence (P0DTC2; Wu et. al. Surface glycoprotein [Severe acute respiratory syndrome coronavirus 2]. NCBI Reference Sequence: YP_009724390.1, Dep. 07/18/2020.) shows that SEQ ID NO: 2 aligns with amino acids N331-P527 of the reference wild-type sequence (Query: SEQ ID NO: 2, Sbjct: P0DTC2):
Query 1 NITNLCPFGEVFNATRFASVYAWNRTRISNCTADYSVLYNSSSFSTFKCYGVNPTKLNDL 60
NITNLCPFGEVFNATRFASVYAWNR RISNC ADYSVLYNS+SFSTFKCYGV+PTKLNDL
Sbjct 331 NITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDL 390
Query 61 CFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDNFTGCVIAWNSNNLDSKVGGNYN 120
CFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPD+FTGCVIAWNSNNLDSKVGGNYN
Sbjct 391 CFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYN 450
Query 121 YLYRLFRKSNLSPFERDISTEIYQAGSTPCNGTEGFNCYFPLQSYGFQPTNGVGYQPYRV 180
YLYRLFRKSNL PFERDISTEIYQAGSTPCNG EGFNCYFPLQSYGFQPTNGVGYQPYRV
Sbjct 451 YLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRV 510
Query 181 VVLSFENLSAPATVCGP 197
VVLSFE L APATVCGP
Sbjct 511 VVLSFELLHAPATVCGP 527
This region of SEQ ID NO: 2 would qualify as a RBD fragment under the definitions of both Smaoui and Lan, and would not be considered the “full” functional RBD domain. Therefore, since the claim is defining a region of a protein that is also claimed by function, and no clear region in the specification has been identified to be representative of what is, and what is not, the RBD of the spike (S) protein of SARS CoV-2, and the art varies as to what is, and what is not, an RBD, the metes and bounds of what is being claimed is unclear.
One suggestion to aid in overcoming this rejection is to remove the recitation of “receptor binding domain (RBD)” from claim 11 and any subsequent claims which may recite this functional region.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claim 11 is rejected on the grounds of being indefinite. Claims 12-17, 21, 23, 25, and 30 are also rejected since they depend from claim 11, but do not remedy these deficiencies of claim 11.
Claims 11 and 18 and dependent claims 12-17, 19-21, 23, 25, and 27-31 thereof 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.
Claim 11 in parts (c) and (d) claim that the nucleotide sequence can encode “at least two peptides”. However, it is unclear if said two peptides are in the same nucleotide sequence (e.g. a fusion/chimeric protein) or if the peptides are on separate open reading frames (ORFs) within the nucleic acid, and only those ORFs encoding the peptides are to be compared for the percent identity claimed. Similarly, in claim 18, it is unclear how a single amino acid sequence can comprise two peptides, as a “peptide” is a short chain of amino acids linked by peptide bonds, while an amino acid sequence is the specific linear order of amino acids in a peptide chain, defining a protein's primary structure. Again, it is unclear if parts (c) and (d) of claim 18 are meaning to claim a single polypeptide which is a chimeric/fusion protein, a polypeptide which comprises multiple antigens/epitopes in the singular polypeptide, or if the claim is intending to claim one or more separate peptides which encode the sequences claimed.
Since a skilled artisan would not be reasonably apprised as to the metes and bounds of the claimed invention, instant Claims 11 and 18 are rejected on the grounds of being indefinite. Claims 12-17, 19-21, 23, 25, and 27-31 are also rejected since they depend from claim 11 or 18, but do not remedy these deficiencies of claim 11 or 18.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 11, 17, 18, 21, 23, 25, and 27-31 rejected under 35 U.S.C. 101 because the claimed invention is directed to naturally-occurring severe acute respiratory syndrome coronavirus type 2 (SARS CoV-2) spike (S) protein sequences and methods of naturally delivering said sequences without significantly more. The claims recite nucleic acid molecules which encode proteins that encode a peptide that is at least 90% identical to SEQ ID NOs: 2, 4, 6, or 8. The methods included in this rejection deliver either the nucleic acid or protein using generically claimed methods that, under broadest reasonable interpretation, read upon delivery of natural SARS CoV-2 virions and products. The immunogenic compositions comprising the nucleic acids or proteins also are recited at a high level of generality so that said compositions do not comprise elements that markedly or significantly alter the claimed material from that which is found naturally.
This judicial exception is not integrated into a practical application because these sequences align with at least 95% or greater identity to known wild-type sequences of SARS CoV-2 S proteins (See ABSS UniProt sequence alignments). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because nothing about the proteins encoded by the nucleic acids markedly or significantly distinguishes them from known wild-type nucleic acid and protein sequences. The methods are recited at such a high level of generality that they read upon methods of natural infection from SARS CoV-2, as there is no specific dose of material delivered, method of delivery, or composition comprising adjuvants or other materials that specifically change the natural products being delivered. Similarly, the immunogenic compositions fail to recite additional elements (e.g. non-natural sequences, heterologous fusion proteins, adjuvants, etc.) that markedly change the products from their naturally-occurring counterparts.
One suggestion is to incorporate limitations from claims not included in this rejection into the independent claims. Another suggestion is to narrow the claimed sequences to clearly read upon those sequences which are not naturally-occurring. These are only suggestions, as applicant is free to amend the claims as they deem necessary or argue that they are drawn to patent-eligible subject matter.
Claim Rejections - 35 USC § 112(a); First Paragraph
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 11-21, 23, 25, and 27-31 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 claims contain 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.
The instant claims are directed to nucleic acids encoding proteins, the proteins encoded thereof, immunogenic compositions comprising said nucleic acids and proteins, and methods of delivering said compositions to elicit therapeutic and/or prophylactic immune responses in a host against SARS CoV-2, wherein the a nucleic acid molecule comprising a nucleotide sequence encoding a SARS-CoV-2 spike protein receptor binding domain (RBD) of sequences at least 90% identical to any one of SEQ ID NOs:2, 4, 6, or 8. The nucleic acid may also encode one or more of these peptides. The “RBD” of SARS CoV-2 is not clearly defined by the specification in that a representative example is not clearly provided, as outlined in the 35 USC 112b rejection supra. Dependent claims 13-14 and 19 provide that the sequence further comprises an oligomerization domain which is at least 90% identical to any one of SEQ ID NOs: 12, 14, 16, 18, and 20. Dependent claims 15-16 and 20 provide that the sequence encodes a self-assembling nanoparticle comprising sequences having about 90% identity to those as in claim 15. With respect to the method claims, the ability to confer resistance/be resistant to SARS CoV-2 infection or strains refers to the ability of the subject to not be adversely affected by that virus.
The claim limitations do not require that the “receptor binding domain” (RBD), the “oligomerization domain”, or the “self-assembling nanoparticle” to possess any particular distinguishing feature or conserved structure, but only that it is a “RBD” from a SARS CoV-2 spike (S) protein polypeptide that comprises a sequence with at least 90% identity to those provided for in the claims. This breadth reasonably encompasses any chimeric proteins, fusion proteins, muteins and variants comprising a protein with at least 90% identity to those claimed. Additionally, the “oligomerization” domains and “nanoparticles” do not have any distinguishing feature, only that these structures must comprise a sequence which is at least 90% identical to those sequences claimed, which reasonably encompasses deletion, insertion, and substitution mutants within any of these claimed protein regions. It is the examiner’s position that the disclosure of the instant application does not convey applicant’s possession of the claimed genera of proteins with at least 90% identity which can act as SARS CoV-2 RBD, those proteins with at least 90% identity which can formulate oligomers, and those proteins with at least 90% identity that can form self-assembling nanoparticles. This analysis also extends to the nucleic acids claimed which encode said proteins, as said nucleic acids are also claimed at the same 90% identity to specific sequences.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings or structural chemical formulas, or by disclosure of relevant, identifying characteristics, i.e., complete/partial structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, by predictability in the art, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
In Regents of the University of California v. Eli Lilly and Co. 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997), the Court decided that adequate written description of genetic material '"requires a precise definition, such as by structure, formula, chemical name, or physical properties,' not a mere wish or plan for obtaining the claimed chemical invention." Id. 43 USPQ2d at 1404 (quoting Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606). The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter of the claim. Id. 43 USPQ2d at 1406. A description of what the genetic material does, rather than of what it is, does not suffice, ld. While the instant claims are drawn to proteins and nucleic acids, the cited case law is relevant because there is limited disclosure of the structure, formula, or physical properties of “SARS CoV-2 S protein RBD", “oligomerization domains”, and “self-assembling nanoparticles” and there is only a disclosure of what these products do (e.g. bind to receptor, form protein aggregates, form protein particles which are nanoscale in size) rather than of what it is (e.g. which sequences bind to the cognate receptor, which sequences can/cannot form aggregates, which sequences can/cannot form nanoscale particles.)
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or of a recitation of structural features common to the members of the genus. Regents of the University of California v. Eli Lilly& Co., 199 F3d 1559, 1569, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997). In Regents of the University of California v. Eli Lilly & Co., the court indicated that, while applicants are not required to disclose every species encompassed by a genus, the description of the genus is achieved by the recitation of a representative number of species falling within the scope of the claimed genus. A "representative number of species" means that the species that are adequately described are representative of the entire 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. MPEP §2163 II.A.3a.ii. Further, even in cases were multiple species with in a claimed genus have been disclosed, such does not necessarily demonstrate possession of the genus. See, In re Smyth, 178 U.S.P.Q. 279 at 284-85 (CCPA 1973) (stating "where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus or combination claimed at a later date in the prosecution of a patent application."); and University of California v. Eli Lilly and Co., 43 USPQ2d 1398, at 1405 (Fed Cir 1997)(citing Smyth for support). Where there is uncertainty in the operability of undisclosed embodiments, an application may be found not to have provided adequate descriptive support for a claimed genus.
The specification discloses the reduction to practice of SEQ ID NOs: 1-8 for the SARS CoV-2 S protein fragments and nucleic acids encoding said fragments. SEQ ID NOs: 11-20 are the multimerization domain (rubrethyrin, ferritin, C4bp, and Lumazine synthase) nucleic acid and protein sequences. SEQ ID NOs: 22-68 are those fusion protein combinations of the SARS CoV-2 S protein fragments and oligomerization domains (nucleic acids and proteins encoded therefrom). These polypeptides, however, do not reflect the breadth of structures of receptor binding domains, oligomerization domains, or self-assembling nanoparticles within each polypeptide sequence as claimed, especially in light of the percent identity claimed. From the limited disclosure, it is unclear which two SARS CoV-2 protein sequences were fused to each other, then which oligomerization domain was joined to the N-terminus of this fusion protein as noted in Fig. 1. Additionally, the SARS CoV-2 RBD sequences are not representative of those within the figures (see 35 USC 112a SOE and 35 USC 112b rejections infra and supra.) Consequently, there is no information about which and how many amino acids are required for generating the RBD, functioning as an oligomerization domain, functioning as a self-assembling nanoparticle, or which sequences or variants thereof would be useful in raising any therapeutic and/or prophylactic immune response against any SARS CoV-2 isolate, mutant, or variant.
There is no disclosure relating similarity of any partial or mutant structure of any of the claimed RBD proteins, oligomerization domains, and/or self-assembling polypeptides to conservation of the associated claimed function, nor is there any association of the breadth of sequences claimed to their ability to be used in therapeutic methods to treat or inhibit SARS CoV-2 infections. It is known for proteins, albeit not in all cases, that amino acid addition(s), substitution(s) or deletion(s) can destroy the function of a peptide epitope or abolish the ability of said protein to perform its wild-type function. For instance, this lack of predictability of the relationship between the protein sequence and the immunogenic epitope function is well documented by Mateu et al. (Mateu MG, et. al. Eur J Immunol. 1992 Jun;22(6):1385-9.) and Greenspan et al. (Greenspan NS, et. al. Nat Biotechnol. 1999 Oct;17(10):936-7.). The effects of these changes are largely unpredictable as to which sequence alterations will have a significant effect versus not. Thus, the specification fails to adequately describe at least a substantial number of members of the RBD sequences, oligomerization domains, and/or self-assembling nanoparticle sequence genera to which the claims are based.
In summary, the art and the specification fail to provide adequate description for the breath of protein sequences claimed which perform the functions as claimed. Furthermore, there was no known or disclosed correlation between these claimed sequences and their immunogenic activity, especially in the treatment or inhibition of SARS CoV-2 infection or disease therefrom. Accordingly, one of skill in the art would not accept the disclosure of the RBD polypeptides, oligomerization domains, and/or self-assembling nanoparticle sequences as representative of the breath of fragments, homologs, or variants thereof that would perform the normal function of said protein, nor is it clear which claimed proteins would have the desired immunogenic activity to be useful in the functions and compositions claimed. Based on the lack of knowledge and predictability in the art, those of ordinary skill in the art would not conclude that the applicant was in possession of the claimed genera of SARS CoV-2 RBDs, oligomerization domains, and/or self-assembling nanoparticles based on the disclosure of the instant application.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (page 1115).
Claims 11-21, 23, 25, and 27-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for SARS CoV-2 S protein fragments as claimed and for fusion proteins comprising said fragments, does not reasonably provide enablement for those SARS CoV-2 S protein fragments with the % sequence identity claimed which comprised receptor binding domains, or fusion protein variants of said proteins which could multimerize and/or form nanoparticles, or nucleic acids which encoded said variants, or the use of any of the claimed nucleic acids or proteins in immunogenic compositions to therapeutically or prophylactically raise a useful immune response against any SARS CoV-2 strain or variant. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). See also MPEP § 2164.01(a) and § 2164.04. Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965). The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
Nature of the invention/Breadth of the claims. The claims are drawn to nucleic acids encoding proteins, the proteins encoded thereof, immunogenic compositions comprising said nucleic acids and proteins, and methods of delivering said compositions to elicit therapeutic and/or prophylactic immune responses in a host against SARS CoV-2, wherein the a nucleic acid molecule comprising a nucleotide sequence encoding a SARS-CoV-2 spike protein receptor binding domain (RBD) of sequences at least 90% identical to any one of SEQ ID NOs:2, 4, 6, or 8. The nucleic acid may also encode one or more of these peptides. The “RBD” of SARS CoV-2 is not clearly defined by the specification in that a representative example is not clearly provided, as outlined in the 35 USC 112b rejection supra. Dependent claims 13-14 and 19 provide that the sequence further comprises an oligomerization domain which is at least 90% identical to any one of SEQ ID NOs: 12, 14, 16, 18, and 20. Dependent claims 15-16 and 20 provide that the sequence encodes a self-assembling nanoparticle comprising sequences having about 90% identity to those as in claim 15. With respect to the method claims, the ability to confer resistance/be resistant to SARS CoV-2 infection or strains refers to the ability of the subject to not be adversely affected by that virus.
State of the prior art/Predictability of the art. With respect to SARS CoV-2 and the spike (S) protein, the glycosylated S proteins cover the surface of SARS-CoV-2 virions and bind to the host cell receptor angiotensin-converting enzyme 2 (ACE2), mediating viral cell entry. When the S protein binds to the receptor, TM protease serine 2 (TMPRSS2), a type 2 TM serine protease located on the host cell membrane, promotes virus entry into the cell by activating the S protein (Huang Y, et. al. Acta Pharmacol Sin. 2020 Sep;41(9):1141-1149. Epub 2020 Aug 3.; p. 1141, ¶ bridging cols.) With a size of 180–200 kDa, the S protein consists of an extracellular N-terminus, a transmembrane (TM) domain anchored in the viral membrane, and a short intracellular C-terminal segment (Huang, Figs. 1-2). S normally exists in a metastable, prefusion conformation; once the virus interacts with the host cell, extensive structural rearrangement of the S protein occurs, allowing the virus to fuse with the host cell membrane. The total length of SARS-CoV-2 S is 1273 aa and consists of a signal peptide (amino acids 1–13) located at the N-terminus, the S1 subunit (14–685 residues), and the S2 subunit (686–1273 residues); the last two regions are responsible for receptor binding and membrane fusion, respectively. In the S1 subunit, there is an N-terminal domain (14–305 residues) and a receptor-binding domain (RBD, 319–541 residues); the fusion peptide (FP) (788–806 residues), heptapeptide repeat sequence 1 (HR1) (912–984 residues), HR2 (1163–1213 residues), TM domain (1213–1237 residues), and cytoplasm domain (1237–1273) residues) comprise the S2 subunit (Huang; Fig. 2a). S protein trimers visually form a characteristic bulbous, crown-like halo surrounding the viral particle (Fig. 1a). Based on the structure of coronavirus S protein monomers, the S1 and S2 subunits form the bulbous head and stalk region. The structure of the SARS-CoV-2 trimeric S protein has been determined by cryo-electron microscopy at the atomic level, revealing different conformations of the S RBD domain in opened and closed states and its corresponding functions (Huang; Fig. 2b, c).
With respect to oligomerization domains fused to viral surface proteins, numerous oligomerization domains are well-documented in the art, and the art is apprised as to the use of these fusion protein constructs to more accurately present viral surface protein antigens to the host immune system in the forms of multimers or nanoparticles (see e.g. Ogun SA, et. al. Infect Immun. 2008 Aug;76(8):3817-23. Epub 2008 May 12.; US20160324958A1; US20180326044A1; US20150174237A1; US20170182151A1.) Display of SARS CoV-2 protein antigens on the surface of self-assembling protein nanoparticles (SAPNs) was suggested in the art (Graham et. al. US20230113170A1), and included the use of ferritin, encapsulin, sulfur oxygenase reductase (SOR), lumazine synthase, and pyruvate dehydrogenase nanoparticles (¶[0065] of Graham.) Graham teaches the testing of Aquifex aeolicus lumazine synthase (LuS) and Helicobacter pylori ferritin as nanoparticle scaffolds, along with the isopeptide bond conjugation system referred to as the SpyTag:SpyCatcher system (¶[0186]). Graham teaches that said proteins were glycosylated to improve protein expression and solubility (¶[0187]), and that various constructs with various glycosylation patterns were studied to determine the most optimal expression system. Conjugation of a prefusion form of the S protein was performed to the various constructs and tested for immunogenicity, structural integrity, and dosage effect (¶[0188-0191]).
Working examples. While data is provided in the figures and figure legends, these working examples disclosed in the specification have little guidance as to the exact constructs which were tested, the dosage and timing of the immunogenic compositions, the comparison to wild-type S protein immunogenicity, and further details of the in vitro/in vivo experimentation performed. For instance, it states that BALB/c mice were inoculated with 2ng DNA in a single vaccination; it is unclear what exact composition was injected into the mice, how the mice were vaccinated (e.g. intramuscular, subcutaneous, intravenous, etc.), if the BALB/c mice expressed humanized ACE2 receptors, what sequence of DNA was used along with whether or not it was presented within an expression vector, etc. While different S protein sequences fused to different oligomerization domains were provided for in the specification, it does not appear as though any mutants of any of these sequences were generated and tested for their ability to 1) bind to the cognate receptor of the S protein, 2) stimulate a SARS CoV-2 immune response that would be therapeutic and/or prophylactic, and/or 3) formulate oligomers and/or nanoparticles. No mutants or variants with at least 90% identity were generated and/or tested, including mutants that encompassed mutations, deletions, and/or insertions that were still 90% identical to the proteins as claimed.
Those “RBD dimers” tested appeared to be attached at the N-terminus to an unidentified scaffold protein (“sc”) and then duplicate RBD domains of SARS CoV-2 S protein (aaR319-K537) were fused end-to-end (Fig. 1). This “RBD” does not appear to coincide with the RBD of any of the claimed sequences of SEQ ID NOs: 2, 4, 6, or 8, as at least SEQ ID NO: 2 only encompasses N331-P527 of the wild-type S protein, while the RBD of Fig. 1 is a much longer amnio acid fragment of said protein. With respect to the claimed oligomerization domains, SEQ ID NO: 12 appears to be rubrerythrin, which is a non-heme iron protein commonly acting as a hydrogen peroxide scavenger in bacteria and archaea, that typically functions as a homodimer. Its oligomerization is structurally defined by a "head-to-tail" arrangement. SEQ ID NO: 14 appears to be ferritin. SEQ ID NOs: 16 and 18 appear to be C4bp domain (IMX313) variants, while SEQ ID NO: 20 appears to be the oligomerization domain for lumazine synthase. It is unclear from the guidance in the specification which one was tested in Fig. 1.
The conditions which induced the “rapid neutralizing antibody response 7 days post infection” as noted in Fig. 3 are unclear. It is unclear if such an immune response is cross-neutralizing to SARS CoV-2 mutants or variants, it is unclear as to the vaccine regimen of Fig. 3, it is unclear as to whether said response was tested in an animal model or clinical setting for actual viral challenge against homologous or heterologous viral strains.
Guidance in the specification. The specification provides guidance towards the generation of SARS CoV-2 S protein fragment fusion proteins, namely SEQ ID NOs: 2, 4, 6, and 8 encoded by SEQ ID NOs: 1, 3, 5, and 7, respectively. The specification provides for said sequences to be fused to the oligomerization domains set forth in SEQ ID NOs: 12, 14, 16, 18, and 20, wherein said sequences are encoded by SEQ ID NOs: 11, 13, 15, 17, and 19, respectively. The specification provides for the full-length sequences of the resulting proteins, where the oligomerization domain appears to be N-terminal to the S protein fragment. It is unclear if mutants of these proteins would perform the claimed functions of acting as a receptor binding domain, an oligomerization domain, have the ability to form nanoparticles, and/or have the ability to elicit therapeutic and/or prophylactic immune responses in any host against any SARS CoV-2 challenge.
Amount of experimentation necessary. Additional research is required in order to determine whether or not the claimed breadth of sequences have the ability to form and perform in the claimed manner, especially in their ability to bind to the cognate SARS CoV-2 receptor, multimerize, form nanoparticles, and/or be useful in immunogenic compositions in a manner to elicit therapeutic and/or prophylactic immune responses against any SARS CoV-2 challenge.
In light of the Supreme Court decision in Amgen Inc. et al. v. Sanofi et al., 143 S. Ct. 1243 (2023) (hereafter Amgen), updated guidelines were provided regarding the assessment of enablement (Federal Register, pp. 1563-1566; Pub. Jan. 10, 2024.) In Amgen, the Supreme Court unanimously affirmed that a genus of monoclonal antibodies were not enabled because when a range within a genus is claimed, there must be reasonable enablement of the scope of the range. The Court found in Amgen that due to the large number of possible candidates within the scope of the claims and the specification's corresponding lack of structural guidance, it would have required undue experimentation to synthesize and screen each candidate to determine which compounds in the claimed class exhibited the claimed functionality. In the instantly claimed invention, the breadth of any of the claimed proteins or nucleic acids encoding said proteins with 90% identity to the numerous claimed sequences is extraordinarily large, and experimentation to determine which mutations would be tolerated, especially to generate stable nucleic acids and/or proteins that would be useful in immunogenic compositions, would be undue. It would be further undue experimentation to determine which sequences still resulted in binding to the cognate receptor, formation of multimers and/or nanoparticles, and/or possessed the ability to elicit therapeutically relevant immune responses in any host. Due to the limited guidance provided for in the specification, it was unclear which sequences delivered in which format (e.g. protein subunit vaccines, nucleic acid vaccines, etc.), using which vaccine regimen (e.g. dosage, delivery route, timing, volume, carriers, excipients, adjuvants, host, etc.) would result in the claimed functions.
For the reasons discussed above, it would require undue experimentation for one skilled in the art to make and/or use the claimed products and methods.
Claims 11-17 are rejected under 35 U.S.C. 112, first paragraph, as containing subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant broadly claims a host cell or vector or nucleic acid containing the nucleic acids of claims 11-17. The claims read on a cell within a transgenic animal or a transgene therein given that the term "isolated" is not denoted in describing the host cell, nucleic acid, or vector.
With respect to the un-isolated host cells and transgenes as “nucleic acids” or “vectors “of the instant claims discussed above, the state of the art at the time of filing was such that one of skill could not predict the phenotype of transgenics. The art of transgenic animals has for many years stated that the unpredictability lies, in part, with the site or sites of transgene integration into the target genome and that "the position effect" as well as unidentified control elements are recognized to cause aberrant expression of a transgene (Wall RJ. Theriogenology, Vol. 45, Pg. 57-68, 1996.)
The elements of the particular construct used to make transgenic animals are also held to be critical, and they must be designed case by case without general rules to obtain good expression of a transgene; e.g., specific promoters, presence or absence of introns, etc. (Houdebine LM. J Biotechnol. 1994 May 31;34(3):269-87.) Furthermore, transgenic animals are regarded to have within their cells certain cellular mechanisms that prevent expression of the transgene, such as methylation or deletion from the genome (Kappel CA, et. al. Curr Opin Biotechnol. 1992 Oct;3(5):548-53.) Houdebine (Houdebine LM. Comp Immunol Microbiol Infect Dis. 2009 Mar;32(2):107-21.) teaches progress has been made in the field of transgenic animals for production of foreign proteins (Abstract); however, constructing an efficient expression vector to produce a therapeutic protein is not a standard operation (p. 116, ¶2). Therefore, undue experimentation is required to make and use a transgene and transgenic animal to produce the therapeutic proteins of the instant claims.
Examples in the literature aptly demonstrate that even closely related species carrying the same transgene construct can exhibit widely varying phenotypes. Mullins et. al. (Mullins JJ, et. al. Hypertension. 1993 Oct;22(4):630-3.) states that not all animals express a transgene sufficiently to provide a model for a disease as the integration of a transgene into different species of animal has been reported to give divergent phenotypes. For example, several animal models of human diseases have relied on transgenic rats when the development of mouse models was not feasible. Mullins et. al. (Mullins JJ, et. al. Nature. 1990 Apr 5;344(6266):541-4.) produced outbred Sprague-Dawley x WKY rats with hypertension caused by expression of a mouse Ren-2 renin transgene. Hammer (Hammer RE, et. al. Cell. 1990 Nov 30;63(5):1099-112.) describes spontaneous inflammatory disease in inbred Fischer and Lewis rats expressing human class I major histocompatibility allele HLA-B27 and human 02- microglobulin transgenes. Both investigations were preceded by the failure to develop human disease-like symptoms in transgenic mice expressing the same transgenes that successfully caused the desired symptoms in transgenic rats (Mullins JJ, et. al. EMBO J. 1989 Dec 20;8(13):4065-72. Erratum in: EMBO J 1990 Mar;9(3):972.) Thus, the use of nonmurine species for transgenesis will continue to reflect the suitability of a particular species for the specific questions being addressed, bearing in mind that a given construct may react very differently from one species to another.
The examiner notes here, in addition to these issues, even assuming in arguendo that a person of ordinary skill in the art could make a host organism with functional transgene that encodes the instantly recited therapeutic protein, there is no predictability that the host will survive its expression. The transgene depends on the host for function and harm to the host, including death, renders the transgene nonfunctional and thus not enabled.
The art is well-aware of side effects caused by therapeutic proteins such as the one instantly recited. In a transgenic cell or animal that expresses the same, the therapeutic protein will exert uncontrolled side effects, as said protein is not administered but chronically present and so such side effects are potentially more deleterious than from an administered therapeutic protein. Hansel et. al. (Hansel TT, et. al. Nat Rev Drug Discov. 2010 Apr;9(4):325-38. Epub 2010 Mar 22.) teaches numerous exemplary side effects from licensed therapeutic proteins, namely monoclonal antibodies, to include: increased bleeding risk, infection, heart failure, cancer, thyroid disorder, autoimmune reactions, and cytokine release syndrome (CRS)(Table 1). One or more such effects may occur with the therapeutic protein instantly recited when administered, and the instantly encoded therapeutic protein may also target related or unrelated proteins in the transgenic host, leading to additional undesirable effects. For at least all these reasons, transgenes are not enabled.
At the time of filing, the phenotype of a transgene and transgenic cell contained within any animal was unpredictable. The claims as written, which encompass a transgene and/or a cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation in order to generate and use the invention. Applicants can obviate the instant rejection by amending the claim to recite the term "isolated" before the recitation of "host cell", “vector”, and/or “polynucleotide/nucleotide” in order to clarify that said features are not within a transgenic animal. Applicant may additionally consider using “purified” if said description is appropriate for such a term and it is not redefined away from standard meaning. Method claims using these products should also carry the appropriate adjectives above.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use functional polynucleotides that produce the instantly claimed therapeutic protein with a reasonable expectation of success in the context of transgenes and/or transgenic animals encompassed by the instant claims. For at least these reasons, the claims are rejected for failing to fully enable the instant claims.
Claim Rejections - 35 USC § 102
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.
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.
(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 11, 17, 18, 21, 23, 25, and 27-31 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Georges et. al. (US20210260180A1, (PGPub of US Pat. App. No. 17/342,769; See ABSS sequence alignments) priority 02/14/2020; hereafter “Georges”.)
The Prior Art
Georges teaches immunogenic compounds, pharmaceutical formulations thereof and their use for inducing a protective immune response against 2019 novel coronavirus (SARS-CoV-2) infection and variants in a mammal (entire document; see abstract.) Georges teaches the immunogenic compositions comprise a replication defective adenoviral (rdAd) vector comprising a nucleic acid sequence encoding SEQ ID NO: 446 or a variant comprising at least 90%, or at least 95% identity to SEQ ID NO: 446, wherein SEQ ID NO: 446 is 97.7% identical to instant SEQ ID NO:8; 95.3% identical to instant SEQ IDNO: 6; 95.8% identical to instant SEQ IDNO: 4; and 95.6% identical to instant SEQ ID NO: 2 (¶[0010]; instant claims 11, 17, 18, 30-31). Georges teaches methods of inducing an immune response against coronavirus (CoV), namely SARS CoV-2, comprising administering an effective amount of the immunogenic composition comprising said rdAd vector encoding the SARS CoV-2 spike (S) protein receptor binding domain (RBD) to a mammalian subject, wherein said rdAd vector delivery leads to transient expression of the encoded SARS CoV-2 antigen proteins or peptides thereof in the mammalian cells (¶[0120]; reference claims 1-3, 44-46; instant claims 21, 23, 25, 27-29). Georges teaches the nucleic acid sequences encoding the SARS CoV-2 RBD may be codon optimized for expression in the target host, such as humans (¶[0013][0123][0215][0457]).
For at least these reasons, Georges teaches the limitations of instant claims 11, 17, 18, 21, 23, 25, and 27-31, and anticipates the invention encompassed by said claims.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 11-21, 23, 25, and 27-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 17-22 of copending Application No. 18/556,414 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both are claiming nucleic acid molecules encoding SARS CoV-2 S protein RBD sequences which are identical (See ABSS sequence alignments), and both are claiming the same formations/structures of said sequences (e.g. tandem repeats of the immunogen). Both claim the sequences are within expression vectors, both claim the sequences are within self-assembling nanoparticles. Both claim the RBD are joined to oligomerization domains from the group IMX313P, ferritin, PcV, and lumazine synthase. Both claim immunogenic compositions comprising these sequences. Both claim methods of using these sequences in vaccination regimens to induce an immune response in a host.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL B GILL whose telephone number is (571)272-3129. The examiner can normally be reached on M to F 8:00 AM to 5:00 PM Eastern.
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/RACHEL B GILL/
Primary Examiner, Art Unit 1671