Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
Priority
This application is a continuation of U.S. Patent Application No. 17/474,732, filed September 14, 2021, which is a continuation of U.S. Patent Application No. 16/416,663, filed May 20, 2019, which is a continuation of U.S. Patent Application No. 14/816,120, filed August 3, 2015, which is a continuation of U.S. Patent Application No. 13/503,828, filed July 9, 2012, which is the U.S. National Phase Application filed under 35 U.S.C. § 371 claiming benefit to International Patent Application No. PCT/US2010/55187, filed November 2, 2010, which is entitled to priority under 35 U.S.C § 119(e) to U.S. Provisional Patent Application Nos. 61/257,450 and 61/257,461, both filed November 2, 2009, that is hereby acknowledged by the Examiner.
Status of the Claims
The amendment dated 09/24/2024 is acknowledged. Claims 1-20 are pending and under examination.
Information Disclosure Statement
There was no information disclosure statement (IDS) submitted at the time of this Office action.
Specification
The specification is objected to because of the following informalities: The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (pg 11). 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. Appropriate correction is required.
Claim Objections
Claim 11 is objected to for the following informalities:
Claim 11 recites “A compositions”. The claim should be recited “A composition comprising”.
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.
Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
The claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claims 1-20 are determined to be directed to laws of nature and natural products. The rationale for this determination is explained below:
The claims are directed to:
Claim 1. An isolated nucleic acid comprising a sequence encoding a protein having one or more sequences selected from the group consisting of: one or more of SEQ ID NOs: 46, 47, 48 and 49 with or without a leader sequence, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, variants with 80% or more homology to SEQ ID NOs: 46, 47, 48 and 49, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, and complements thereof;
Claim 2. The nucleic acid of claim 1, wherein the sequence is selected from the group consisting of: SEQ ID NOS: 31, 33, 35 and 37 with or without coding sequence for a leader sequence, complements thereof, fragments thereof encoding at least 20 amino acids, complements thereof, nucleic acid molecules 80% or more homologous to SEQ ID NOS: 31, 33, 35 and 37, complements thereof, fragments thereof encoding at least 20 amino acids, and complements thereof;
Claim 8. A vaccine comprising a nucleic acid of claim 1 and/or one or more proteins selected from the group consisting of SEQ ID NOs: 46, 47, 48 and 49 with or without a leader sequence, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, variants with 80% or more homology to SEQ ID NOs: 46, 47, 48 and 49, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, and complements thereof.
Claim 11. A compositions comprising one or more proteins selected from the group consisting of SEQ ID NOs: 46, 47, 48, and 49 with or without a leader sequence, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, variants with 80% or more homology to SEQ ID NOs; 46, 47, 48 and 49, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, and complements thereof.
The specification discloses that the nucleic acid sequences of the invention are “consensus” sequences based on naturally occurring FMDV sequences. However, the claims are broad enough to encompass nucleic acid sequences that have the same nucleotide sequences as in naturally occurring FMDV genes.
[page 1] …FMDV is a single-stranded, positive-sense RNA genome of approximately 8500 bases surrounded by an icosahedral capsid with 60 copies each of four structural proteins VP1-4 and is antigenically highly variable with several subtypes including A, Asia 1, O, C, SAT1, SAT2, and SAT3. Recent outbreaks of foot-and-mouth disease in a number of previously disease free countries including Taiwan in 1997, United Kingdom and Netherlands in 2001, and the emergence in several South American countries has risen the awareness of the economically destructive virus.
[page 2] Provided herein is an isolated nucleic acid comprising a sequence encoding the consensus amino acid sequence of VP1-4 of foot-and-mouth disease virus subtypes A, Asia 1, C, O, SAT1, SAT2, SAT3, SAT4, or a complement thereof….
Here, the claimed isolated nucleic acid can be compared to its naturally occurring counterpart in its natural state, namely to the corresponding nucleic acid sequences found in naturally occurring FDMV sequences (including naturally occurring variants). The claimed nucleic acid molecule is “isolated,” which could be interpreted to mean that the nucleic acid has a different structural characteristic than the naturally occurring FDMV genes, because the chemical bonds at each end have been severed in order to isolate it from the chromosome on which it occurs in nature.
Nevertheless, the claims broadly encompass nucleic acid sequences that have the same nucleotide sequence as in naturally occurring FDMV viral sequences, notwithstanding this isolation.
Specifically, the claim terminology “without a leader sequence” and “variants with 80% or more homology…” and “nucleic acid molecules 80% or more homologous…” cause the claims to read on naturally occurring viral sequences found in nature, and the recitation of an “isolated” nucleic acid molecule fails to add significantly more. For example, Cao et al. (CN101270155, May 6, 2008) discloses a FMDV virus P12A protein (SEQ ID NO: 2 and claim 2 of Cao) used in the invention that has 90.7% sequence identity to SEQ ID NO: 46 of the present invention. Accordingly, naturally occurring FMDV gene sequences would read on the claimed nucleic acids encoding protein “variants with 80% or more homology to” at least SEQ ID NO: 46 and to “nucleic acid molecules 80% or more homologous to” at least SEQ ID No: 46.
The claims are directed to an ineligible ‘production of nature’ exception.
There are no apparent differences in structure, biological or pharmacological functions or activities, or other properties relative to the naturally occurring counterpart.
Eligibility Step 1: Is the claim directed to a process, machine, manufacture or composition of matter?
Answer to Step 1: Yes, claims 1 and 2 are directed to a nucleic acid, which is a composition of matter.
Eligibility Step 2A: Is the claim directed to a law of nature, a natural phenomenon (product of nature) or an abstract idea?
Answer to Step 2A Prong 1: Yes, claim 1 is directed to a nature-based product falling under the "product of nature” exception (i.e., a law of nature or natural phenomenon claimed as a physical product).1
Note that the specification defines “variant” with respect to a polypeptide to include “a protein with an amino acid sequence that is substantially identical to a referenced protein with an amino acid sequence that retains at least one biological activity” (page 16). The specification also defines “variant” with respect to a nucleic acid as follows:
“Variant” used herein with respect to a nucleic acid may mean (i) a portion or fragment of a referenced nucleotide sequence; (ii) the complement of a referenced nucleotide sequence or portion thereof; (iii) a nucleic acid that is substantially identical to a referenced nucleic acid or the complement thereof; or (iv) a nucleic acid that hybridizes under stringent conditions to the referenced nucleic acid, complement thereof, or a sequences substantially identical thereto.
Thus, the specification defines “variants” as distinguished from a reference sequence (in this case from the even-numbered protein SEQ ID Nos in claim 1, and from the odd-numbered nucleic acid sequences in claim 2). However, this terminology does not require, for example, that the variant is not naturally occurring.
The claim term “homology” is also indicated to refer to alignment or comparison of sequences to each other. See specification on page 11: “Homology of multiple sequence alignments may generated using ClustalW (http://wwww.ebi.ac.uk/Tools/clustalw2/index.html).” Alignments of this sort can be made between the claimed SEQ ID Nos and naturally occurring counterpart sequences, thus reading on 'homologous.'4 The term “homology” is understood to encompass the narrower, more specific term “identity,” in which amino acids are identical to each other.
Accordingly, naturally occurring variant sequences having 80% or more identity to those claimed would read on the claimed “variants with 80% or more homology…” and on the claimed “nucleic acid molecules 80% or more homologous to…” in claims 1 and 2, respectively.
The claimed nucleic acid sequences are different, but not markedly different, than naturally occurring counterparts in their natural state. The claimed nucleic acid has no different functional characteristics, in that it encodes the same protein(s) as the natural gene.
The specification also suggests that the nucleic acid molecules of the invention, or their encoded proteins, may be effective in eliciting a broad immune response against multiple FDMV species. However, claims 1 and 2 broadly encompass nucleic acids having the same nucleotide sequences as naturally occurring FMDV sequences, and thus are not necessarily special “consensus” sequences that differ in any way from their naturally occurring counterparts.
There are no apparent differences in structure, biological or pharmacological functions or activities, or other properties relative to the naturally occurring counterpart.
See MPEP 2106.04(c)(II)(C)(2):
In Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. The patentee in Myriad had discovered the location of the BRCA1 and BRCA2 genes in the human genome, and isolated them, i.e., separated those specific genes from the rest of the chromosome on which they exist in nature. As a result of their isolation, the isolated genes had a different structural characteristic than the natural genes, i.e., the natural genes had covalent bonds on their ends that connected them to the rest of the chromosome, but the isolated genes lacked these bonds. However, the claimed genes were otherwise structurally identical to the natural genes, e.g., they had the same genetic structure and nucleotide sequence as the BRCA genes in nature. The Supreme Court concluded that these isolated but otherwise unchanged genes were not eligible, because they were not different enough from what exists in nature to avoid improperly tying up the future use and study of the naturally occurring BRCA genes. See, e.g., Myriad, 569 U.S. at 585, 106 USPQ2d at 1977 ("Myriad's patents would, if valid, give it the exclusive right to isolate an individual’s BRCA1 and BRCA2 genes … But isolation is necessary to conduct genetic testing") and 569 U.S. at 593, 106 USPQ2d at 1980 (describing how would-be infringers could not avoid the scope of Myriad’s claims). In sum, the claimed genes were different, but not markedly different, from their naturally occurring counterparts (the BRCA genes), and thus were product of nature exceptions.
Eligibility Step 2A, Prong 2: Does the claim recite additional elements that integrate the judicial exception (natural product) into a practical application?
Answer to Step 2A Prong 2: No, claims 1 and 2 do not recite any additional elements beyond the judicial exception.
The claims are directed only to the isolated nucleic acid. Thus, the claim encompasses a ‘product of nature’ exception which is not integrated into any practical application, because there is no practical application recited or required by the claim.
Eligibility STEP 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
Answer to Step B: No, claims 1 and 2 recite only a product of nature, without any additional elements/features, as discussed in the Step 2A Prong 2 analysis above.
Claims 1-20 are directed to an ineligible “product of nature” judicial exception without significantly more because the claimed "isolated" nucleic acids encompass embodiments that are otherwise identical in nucleotide sequence to naturally occurring counterparts, namely to naturally occurring foot-and-mouth disease virus genes.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-2, 8 and 11 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 contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed to (claim 1) an isolated nucleic acid comprising a sequence encoding a protein having one or more sequences selected from the group consisting of: one or more of SEQ ID NOs: 46, 47, 48 and 49 with or without a leader sequence, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, variants with 80% or more homology to SEQ ID NOs: 46, 47, 48 and 49, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, and complements thereof; (claim 2) the nucleic acid of claim 1, wherein the sequence is selected from the group consisting of: SEQ ID NOS: 31, 33, 35 and 37 with or without coding sequence for a leader sequence, complements thereof, fragments thereof encoding at least 20 amino acids, complements thereof, nucleic acid molecules 80% or more homologous to SEQ ID NOS: 31, 33, 35 and 37, complements thereof, fragments thereof encoding at least 20 amino acids, and complements thereof; (claim 8) a vaccine comprising a nucleic acid of claim 1 and/or one or more proteins selected from the group consisting of SEQ ID NOs: 46, 47, 48 and 49 with or without a leader sequence, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, variants with 80% or more homology to SEQ ID NOs: 46, 47, 48 and 49, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, and complements thereof; and (claim 11) a compositions comprising one or more proteins selected from the group consisting of SEQ ID NOs: 46, 47, 48, and 49 with or without a leader sequence, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, variants with 80% or more homology to SEQ ID NOs; 46, 47, 48 and 49, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, and complements thereof.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
The ground for the written description rejection is as follows: In this case, the claims are directed to a genus of nucleic acid molecules that encode a protein with 80% or more homology to SEQ ID NOs: 46-49 and dependent claims with an 80% homology to SEQ ID NOs: 31, 33, 35 and 37; however, the specification does not provide support for what amino acid changes qualify as "homologous". Thus, the claims encompass a broad genus of polypeptides, as the degree of homology is nebulous in the absence of a definition of exactly what changes are envisioned by those terms.
According to the claims, homologous changes can be made to the sequence (note the difference between sequence homology and sequence identity) provided that the altered sequence remains 80% homologous to the base sequences of SEQ ID NOs: 46-49, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, and complements thereof. The specification does not provide a defined list of which amino acid mutations qualify as "homologous". A nucleic acid sequence having 80% sequence homology to SEQ ID NOs: 46-49, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, and complements thereof can have any type of mutation (e.g., deletion, insertion, substitution), anywhere along the nucleic acid sequence. It does not appear applicants were in possession of the claimed nucleic acid sequences having 80% homology to SEQ ID NOs: 31, 33, 35, 37 and 46-49, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, and complements thereof at the time of filing.
Given that there is no identification of any particular portion of the structure that must be conserved, the specification does not provide adequate written description of the claimed genus. While it is possible to make proteins, as well as protein fragments of FMDV, the specification must provide an adequate description of the genus. The provision of a partial structure and a function without a nexus between the two does not put one in possession of the large genus of variants encompassed by the claims.
Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 1111, clearly states that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117). The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116). Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC 112 is severable from its enablement provision (see page 115). Adequate written description requires more than a mere statement that it is part of the invention and a reference to a potential method of isolating it. The polypeptide itself is required. See Fiers v. Revel, 25 USPQ 2d 1601 at 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Lts., 18 USPQ2d 1016. Furthermore, In The Reagents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412), the court held that a generic statement which defines a genus of nucleic acids by only their functional activity does not provide an adequate written description of the genus. The court indicated that while Applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a representative number of DNA molecules, usually defined by a nucleotide sequence, falling within the scope of the claimed genus. At section B(1), the court states that "An adequate written description of a DNA...'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".
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus. In view of the lack of disclosure of how to make the construct having 80% homology to claimed sequences, the claims are rejected as lacking adequate descriptive support for the claimed invention.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1, 3, 8 and 11 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Cao et al. “Cao” (CN101270155, May 6, 2008).
The claims are directed to an isolated nucleic acid comprising a sequence encoding a protein having one or more sequences selected from the group consisting of: one or more of SEQ ID NOs: 46, 47, 48 and 49 with or without a leader sequence, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, variants with 80% or more homology to SEQ ID NOs: 46, 47, 48 and 49, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, and complements thereof. Note: It is understood by the Office that limitation of said SEQ ID NOs. do not require a leader sequence. Thus, the limitation of sequence identity and/or homology can be met by prior art sequences not containing a leader sequence as well as immunogenic fragments comprising at least 20 contiguous amino acids; and variants with 80% homology would anticipate said claims.
Regarding claims 1, 3, 8 and 11, Cao discloses “a method for assembling foot-and-mouth disease virus empty capsids in insect cells via the alteration of acid-resistance. The method for assembling foot-and-mouth disease virus empty capsids in insect cells includes the following steps: (1) the altered P12A gene and the non-structural protein gene 3C of foot-and-mouth disease virus are introduced into bacteria via baculovirus vectors for recombination to produce recombinant rhabdovirus A; (2) the DNA of the recombinant rhabdovirus A is used to transfect the insect cells, so that the foot-and-mouth disease virus empty capsids are obtained. The method assembles the integral foot-and-mouth disease virus empty capsids in the insect cells for the first time, lays a foundation for the research and the development of gene-engineered subunit vaccines and novel diagnostic reagents” (Abstract). Cao discloses a FMDV virus P12A protein (SEQ ID NO: 2 and claim 2 of Cao) used in the invention that has 90.7% sequence identity to SEQ ID NO: 46 of the present invention (see below). Further, 20 contiguous amino acids from SEQ ID NO: 2 of Cao has 100% identity to 20 contiguous amino acids in SEQ ID NO: 46, thereby reads on an immunogenic fragment comprising at least 20 amino acids of the present invention.
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Therefore, the cited prior art anticipates the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 5-7 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Cao et al. “Cao” (CN101270155, May 6, 2008) as applied to claim 1 above, in view of Fange et al. “Fang” (US PGPUB 2004/0265955). The teachings of Cao are outlined above and incorporated herein.
The claims are directed to an isolated nucleic acid comprising a sequence encoding a protein having one or more sequences selected from the group consisting of: one or more of SEQ ID NOs: 46, 47, 48 and 49 with or without a leader sequence, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, variants with 80% or more homology to SEQ ID NOs: 46, 47, 48 and 49, complements thereof, immunogenic fragments thereof comprising at least 20 amino acids, and complements thereof.
Although Cao discloses SEQ ID NO: 46 comprising immunogenic fragments thereof comprising at least 20 amino acids; variants with 80% or more homology to SEQ ID NO: 46, Cao does not explicitly teach a leader sequence wherein the leader sequence is an Ige leader sequence in a plasmid expression vector.
Fang, however, teaches that an FMDV plasmid may code for an immunoglobulin heavy or light chain, or a fragment thereof, and that such a plasmid may include an IgE heavy or light chain (or fragment thereof) to ensure protein secretion following synthesis (para. [0149] and [0072]; para. [0039] and [0040]; page 81).
Accordingly, it would have been obvious to one of ordinary skill in the art to generate an isolated nucleic acid comprising a sequence encoding a protein having SEQ ID NO: 46 as disclosed by Cao, whereby an IgE leader sequence is combined with the nucleic acid as taught by Fang. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success for the benefit of ensuring “protein secretion following synthesis” (para. [0149] and [0072]; para. [0039] and [0040]; page 81) of the desired immunogenic peptide. Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Barry Chestnut whose telephone number is (571) 270-3546. The examiner can normally be reached on M-Th 7:00 am – 5:00 pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Janet Andres can be reached on 571-272-0867. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BARRY A CHESTNUT/Primary Examiner, Art Unit 1672
