DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on January 16, 2026 is acknowledged.
Applicant's election with traverse of species E in the reply filed on January 16, 2026 is also acknowledged. The traversal is on the grounds that species B, C, and D have the same inventive concept as E since species B, C, and D are encompassed within E.
Applicant’s traversal for the species listed for Group I is found persuasive and the species requirement for Group I is withdrawn.
Claims 1-27 are pending; claims 7 and 9-27 are withdrawn due to non-elected subject matter; and claims 1-6 and 8 are under consideration.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/6/2023 has been considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in paragraphs [0296, 0301, and 0316] of the instant published disclosure, USPgPub 2024/0139306. 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.
The use of at least term: “GenBank” in paragraph [0302] in the instant published disclosure are trade names or marks used in commerce. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Applicant is required to properly annotate all trade names and/or marks present in the instant specification, if any additional trade names and/or marks are discovered. Applicant' s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claim 1 is objected to because of the following informalities: the article, “a” is missing prior to “porcine” in lines 3 and 8. The “a” recited in line 7 prior to “SEQ ID NO: 44” is extraneous. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-6 and 8 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 1 is drawn to an isolated nucleic acid “comprising” a nucleotide sequence “selected from the group of”, followed by a list of four groupings of nucleic acid sequences separated by “and” in line 7. MPEP § 2173.05(h) requires a Markush grouping to be a closed group of alternatives, i.e., the selection is made from a group “consisting of” (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. In contrast, the list of nucleotide sequences recited in claim 1 is openly comprising. It is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022) (each independent claim recites "a selection from the group comprising a person, an animal, an animated character, a creature, an alien, a toy, a structure, a vegetable, and a fruit." … (emphasis added). "Given the breadth of variation among the specified alternatives and the use of the open-ended word ’comprising’ to define the scope of the list, we affirm the Board's conclusion that the pending claims recite improper Markush language and are indefinite under § 112(b)."). If a claim is intended to encompass combinations or mixtures of the alternatives set forth in the Markush grouping, the claim may include qualifying language preceding the recited alternatives (such as "at least one member" selected from the group), or within the list of alternatives (such as "or mixtures thereof"). Id. at 1281. See also MPEP § 2111.03. In the instant case, the nucleic acid molecules claimed “encompasses a massive number of distinct alternative members”… “since one skilled in the art cannot determine its metes and bounds due to an inability to envision all of the compounds defined by the Markush groups”. All quoted passages are from MPEP § 2173.05(h).
Lines 3-4 of claim 1 is drawn to, “a nucleotide sequence comprising a genome sequence of porcine morbillivirus of SE[[ ]]Q ID NO: 44”. It is unclear whether the nucleotide sequence is intended to encompass the entire length of SEQ ID NO: 44 or any sequence fragment of indeterminable length within “a genome sequence of SEQ ID NO: 44. This rejection could be ameliorated if the claim is amended to language such as, “a nucleotide sequence comprising the genome sequence of porcine morbillivirus of SEQ ID NO: 44”.
The nucleic acids encompassed by: a nucleotide sequence which encodes at least 5 contiguous nucleotides amino acids of SEQ ID NO: 45, 48, or 49; and a nucleotide sequence encoding the amino acid sequence of porcine morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein, encompass an exponential quantity of nucleotide sequences. Amino acids SEQ ID NOs: 45, 48, and 49 comprise 523, 557, and 607 amino acid residues respectively, corresponding to 3,058,212,690, 3,942,747,415, and 5,490,526,251 nucleic acid sequences encoding at least 5 contiguous amino acids of each sequence (using combinatorial and binomial coefficient calculations). Calculations to determine the quantity of nucleotide sequences requiring at least 6, 7, or 8, contiguous amino acids of SEQ ID NOs: 45, 48, and 49, etc., also encompassed by claim 1, and the possible number of epitopes of claim 8 encoded by any of the nucleic acid molecules of claim 1, was not attempted.
Also not attempted was a calculation to determine the quantity of nucleotide sequences encoding (emphasis underlined), “the amino acid sequence of porcine morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein”. Is the amino acid sequence “of” encompassing partial sequences of “at least 5 contiguous amino acids”, due to context previously recited? Or does the instant amino acid sequence mean the entirety of a porcine morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein? In either case, the metes and bounds of the amino acids claimed cannot be determined because the hallmarks establishing an amino acid sequence and the corresponding nucleic acids encoding a morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein as “porcine” has not been established (discussed below). The skilled artisan would be unable to determine the metes and bounds of boundless nucleotide sequences encompassed by claim 1. This rejection affects all dependent claims.
Claim 5 recites the limitation "recombinant" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 5 encompasses the limitations of claims 3 and 4, reciting a vector. The vector, further characterized as recombinant in claim 5, blurs the claim scope because requisite components requiring expression are inherently present in a virus that is not recombinant, encompassed by “vector” in paragraph [0063] of the instant published disclosure, USPgPub 2024/0139306.
Claim 8 recites the limitation "immunotherapeutic" in line 1. There is insufficient antecedent basis for this limitation in the claim. There is no previous recitation for the intended use characterizing the composition as immunotherapeutic. The intended use is not clear.
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 1-4 and 8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature, without significantly more. Instant claim 1 recites an isolated nucleic acid molecule comprising a nucleotide sequence selected from the group of:
a nucleotide sequence comprising a genome sequence of porcine morbillivirus of SEQ ID NO: 44;
a nucleotide sequence which encodes at least 5 contiguous nucleotides amino acids of SEQ ID NO: 45, 48, or 49;
a nucleotide sequence having at least 90% sequence identity to a SEQ ID NO:44; and
a nucleotide sequence encoding the amino acid sequence of porcine morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein.
Claim 2 recites a nucleotide construct comprising the nucleic acid molecule of claim 1 operably linked to a promoter. Claim 3 recites a vector comprising the construct and claim 4 recites a cell comprising the vector. Claim 8 recites an immunotherapeutic comprising a porcine morbillivirus epitope encoded by the nucleic acid molecule.
Paragraphs [0021, 0291-0305] and Figure 3, teach isolating and characterizing a previously unidentified virus, referred to by the inventors as porcine morbillivirus, from twenty-two porcine fetuses associated with a variable degree of fetal mortality in Mexico from a commercial breeding herd. The reference sequence for the isolated full-length porcine morbillivirus genome is instant SEQ ID NO: 44, recited in instant claim 1. However, there is no evidence in the instant disclosure that the genomic nucleotide sequence comprising SEQ ID NO: 44 or the nucleoprotein corresponding to SEQ ID NO: 45 or the fusion corresponding to SEQ ID NO: 48 or the hemagglutinin protein corresponding to SEQ ID NO: 49, or any 5 contiguous amino acids, and epitopes thereof, claimed, have been recombinantly modified. Therefore, nucleic acids encoding SEQ ID NOs: 44, 45, 47, and 48, any 5 contiguous amino acids and epitopes thereof, are naturally occurring.
Similar to the fact pattern described in Myriad, the genetic information or genetic structure of the instant porcine morbillivirus, possessing genomic SEQ ID NO: 44, comprising SEQ ID NOs: 45, 48, 49, any 5 contiguous amino acids, and epitopes thereof, are not created or altered upon isolation from their native environment. Finding or discovering an important structure does not satisfy the §101 inquiry. Isolation by severing chemical bonds naturally the genome from the remainder of the naturally-occurring virus components does not in itself provide a markedly different characteristic from any porcine morbillivirus, possessing genomic SEQ ID NO: 44, comprising SEQ ID NOs: 45, 48, and 49, or encoding at least 5 contiguous amino acids, or epitope sequences of any of the preceding, found in nature since there are no chemical changes resulting from the isolation.
Since an assumption cannot be made that the nucleic acid molecules, the promoter, the vector, and the cell, recited in claims 2-4, comprise heterologous sequences, the nucleic acid sequences, vector, and cell comprise naturally-occurring porcine morbillivirus sequences, possessing genomic SEQ ID NO: 44 comprising SEQ ID NOs: 45, 48, 49, any 5 contiguous amino acids, and epitopes thereof, are not distinguished as they exist in nature. Therefore, the instant claims recite natural phenomenon according to Step 2A in MPEP § 2106.04(II). The comparison between the material claimed and a porcine morbillivirus, does not indicate a difference in structure, function, or other characteristics, as evidenced by instant paragraphs [0021, 0291-0305] and Figure 3. Therefore, the claimed porcine morbillivirus possessing genomic SEQ ID NO: 44 comprising SEQ ID NOs: 45, 48, 49, any 5 contiguous amino acids, and epitopes thereof, the vector, and cell, are nature exception products. See Association for Molecular Pathology v. Myriad Genetics Inc., 569 U.S. 576, 589-90 (2013) (naturally occurring things are "products of nature" which cannot be patented). Accordingly, analysis must therefore proceed to Step 2A Prong Two.
Step 2A Prong Two requires eligibility analysis to evaluate whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. The instant claims recite no additional element that distinguishes the instantly claimed porcine morbillivirus possessing genomic SEQ ID NO: 44 comprising SEQ ID NOs: 45, 48, and 49, any 5 contiguous amine acid sequences, and epitopes thereof. Instant claim 8 further states that a porcine morbillivirus epitope is encompassed in an "immunotherapeutic composition". However, recitation of "immunotherapeutic composition", fails to meaningfully limit the claim because it is at best the equivalent of merely adding the words "apply it" to the judicial exception. The presence of a possible pharmaceutical carrier, vehicle, and/or excipient does not change the nature or properties of the naturally-occurring the naturally-occurring porcine morbillivirus materials. Accordingly, recitation of an "immunotherapeutic composition" does not integrate the recited judicial exception into a practical application that is patent eligible pursuant to the Supreme Court decision in Association for Molecular Pathology V. Myriad Genetics, Inc. -U.S.-(June 13, 2013).
(Examiner note: recitation of heterologous elements to the nucleic acids claimed, such as signaling, termination or promoter sequences, discussed in paragraph [0078] of the instant published disclosure, for example, would distinguish the instant nucleic acid sequences from those that are naturally occurring.)
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 1-6 and 8 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. This is a written description rejection.
Instant claim 1 recites an isolated nucleic acid molecule comprising a nucleotide sequence selected from the group of (recitations of claim 1 that fail to meet the written description requirements of claim 1 are underlined):
a nucleotide sequence comprising a genome sequence of porcine morbillivirus of SEQ ID NO: 44;
a nucleotide sequence which encodes at least 5 contiguous nucleotides amino acids of SEQ ID NO: 45, 48, or 49;
a nucleotide sequence having at least 90% sequence identity to a SEQ ID NO:44; and
a nucleotide sequence encoding the amino acid sequence of porcine morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein.
Claim 2 recites a nucleotide construct comprising the nucleic acid molecule of claim 1 operably linked to a promoter. Claim 3 recites a vector comprising the construct and claim 4 recites a cell comprising the vector. Claim 5 identifies the expression vector as a baculovirus. Claim 6 is drawn to a method of producing a porcine morbillivirus by transfecting a host cell with a nucleic acid of claim 1 or a vector comprising the nucleic acid of claim 1, allowing replication of the polynucleotide or vector in the host cell, and harvesting the produced porcine morbillivirus from the medium and/or cells. Claim 8 recites an immunotherapeutic comprising a porcine morbillivirus epitope encoded by the nucleic acid molecule. The instant disclosure fails to adequately describe the genus of nucleotide sequences which encode at least 5 contiguous nucleotides amino acids of SEQ ID NO: 45, 48, or 49, or a nucleotide sequence encoding the amino acid sequence of porcine morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein, recited in claim 1 or a porcine morbillivirus epitope encoded by any of the nucleic acid molecules of claim 1, recited in instant claim 8.
Paragraphs [0078-0081] discuss polynucleotide sequences encompassed by the instant claims representing contiguous or non-contiguous nucleotides of the porcine morbillivirus (PoMV). However, the disclosure fails to adequately describe the scope of nucleic acids claimed.
The nucleic acids encompassed by: a nucleotide sequence which encodes at least 5 contiguous nucleotides amino acids of SEQ ID NO: 45, 48, or 49; and a nucleotide sequence encoding the amino acid sequence of porcine morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein, recited in claim 1, encompass an exponential quantity of nucleotide sequences. Amino acids SEQ ID NOs: 45, 48, and 49 comprise 523, 557, and 607 amino acid residues respectively, corresponding to 3,058,212,690, 3,942,747,415, and 5,490,526,251 nucleic acid sequences encoding at least 5 contiguous amino acids of each sequence (using combinatorial and binomial coefficient calculations). Calculations to determine the quantity of nucleotide sequences requiring at least 6, 7, or 8, contiguous amino acids of SEQ ID NOs: 45, 48, and 49, etc., also encompassed by claim 1, and the possible number of epitopes of claim 8 encoded by any of the nucleic acid molecules of claim 1, was not attempted. The scope of nucleic acids claimed, encoding at least 5 consecutive amino acids of SEQ ID NOs: 45, 48 or 49 of claims 1-6 and any epitope encoded by any of the nucleic acids of claim 8, have not been adequately described in the instant disclosure.
The instant specification does not teach one epitope. As taught in Greenspan et al (Nature Biotechnology.1999; 7: 936-937), defining epitopes is not as easy as it seems (page 937). Epitopes have been defined in terms of the spacial organization of residues that make contact with a ligand and the structural characterization of the molecular interface for the binding of the molecules to define the epitope boundaries (page 937 middle of page). The epitope defined in this manner will likely include residues that contact the ligand but are energetically neutral or even destabilizing to binding. “In addition, a priori it will not include any residue that makes no contact with a ligand but whose substitution may profoundly effect ligand recognition through influence on the stability of the free form of the macromolecule, or participation in long-range allosteric effects”. “Even when the residues making contacts with ligands are known with certainty, say from the crystal structure of the complex, the question remains with regard to the energetic involvement of each residue (page 936 right column, first paragraph). Therefore, “amino acids should be recognized to have multiple ways of contributing to a noncovalent interaction” (page 937, middle of page). As evidenced by Greenspan et al a number of factors not primarily related to the contours of the contacts of the molecules contribute to the free energy change, sometimes profoundly. The skilled artisan would be unable to predict or recognize requisite amino acid residues encoded by the exponential quantity of nucleotide sequences encompassed by claim 1 and identify the amino acids as an epitope.
The quantity of nucleotide sequences encoding (emphasis underlined), “the amino acid sequence of porcine morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein” is undeterminable. It cannot be determined whether the amino acid sequence “of” encompasses partial sequences of “at least 5 contiguous amino acids”, due to context previously recited, or whether the amino acid sequence “of” means the entirety of a porcine morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein. In either case, the metes and bounds of the amino acids claimed cannot be determined because the hallmarks establishing an amino acid sequence and the corresponding nucleic acids encoding a morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein as “porcine” has not been established. The skilled artisan would be unable to determine the metes and bounds of boundless nucleotide sequences encompassed by claim 1.
The scope of nucleic acids claimed are not particular to a morbillivirus specific to porcine, as claimed and required. Nucleic acid sequence, GenEmbl database accession no: KC802221 by Verburgh et al Jul-2013, shares 83.1% identity with a nucleic acid sequence encoding SEQ ID NO: 45. GenEmbl database accession no: PP850119 by Jo et al. May 2024, shares 88% identity with a nucleic acid sequence encoding SEQ ID NO: 45. GenEmbl database accession no: AY964108 by Pardo et al Mar-2005, shares 85.3% identity with a nucleic acid sequence encoding SEQ ID NO: 48. GenEmbl database accession no: MZ312422 by Wells et al. Jul-2022, shares 90.5% identity with a nucleic acid sequence encoding SEQ ID NO: 48.GenEmbl database accession no: KF835416 by Espinal et al 2014 shares 62.5% identity with a nucleic acid sequence encoding SEQ ID NO: 49, and GenEmbl database accession no: PP850120 by Jo et al May-2024 shares 81.4% identity with a nucleic acid sequence encoding SEQ ID NO: 49. Each sequence alignment shows several stretches of amino acids of at least 5 contiguous residues. See the sequence alignments provided. The scope of nucleic acids claimed bear no resemblance to a porcine morbillivirus, as asserted. GenEmbl KC802221 is sourced from phocine subjects. GenEmbl AY964108 and KF835416 are identified from canine distemper viruses. GenEmbl PP850119 and PP850120 are derived from a marmoset morbillivirus and GenEmbl MZ312422 is obtained from Phyllostomus bat morbillivirus. Given that the GenEmbl database sequence alignments share between 62.5% and 90.5% sequence identity with nucleic acids encoding the full-length sequences of SEQ ID NOs: 45, 48, and 49, and possess multiple stretches of amino acid sequences having 100% identity to at least 5 contiguous amino acids of SEQ ID NOs: 45, 48, and 49, the claims encompass nucleic acids unrelated to porcine morbillivirus and the specification does not reasonably convey possession of these nucleic acids.
There is no structural motifs or patterns provided in the instant disclosure that would identify the instant morbillivirus nucleic acids claimed as porcine. Yadav et al. (Canadian journal of microbiology. 2019; 65 (11):783-94) describe morbillivirus host expansion in previously unsusceptible hosts based on major morbillivirus receptor structures and evolving hemagglutinin protein receptor binding domains on the virus. Yadav et al. review canine distemper infections among canids, including the Giant panda, Amur tiger and Brown hyena and nonhuman primates; measles infectious in humans and nonhuman primates; and peste-des-petits ruminants’ virus infecting cattle and small ruminants. See the abstract, Introduction, Table 2, and Discussion. While no porcine morbillivirus receptor analysis is provided in the instant specification, paragraph [0316] of USPgPub 2024/0139306 concludes that “PoMV may also utilize CD46 as a cell receptor similar to some strains of MeV”. Provided the high sequence identity ranging between 62.5% and 90.5% of the instant nucleic acids with phocine morbillivirus, canine distemper virus, marmoset morbillivirus, and Phyllostomus bat morbillivirus, according to the sequence alignments provided, the skilled artisan would not predict that the instant nucleic acids are species specific to porcine subjects.
The applicable standard for the written description requirement can be found in MPEP 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. V. Gen-Probe Inc., 63 USPQ2d 1609; Vas- Cath Inc. V. Mahurkar, 19 USPQ2d 1111; and University of Rochester V. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004). 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. In this case, the only factor present in the specification are nucleic acid sequences comprising at least 90% identity to SEQ ID NO: 44.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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). Conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
There is no disclosure of sufficient characteristics of the nucleic acids claimed to allow persons of ordinary skill in the art to recognize that applicants were in possession of the exponential quantity of nucleotide sequences encompassed by claims. The specification does not provide adequate written description of the nucleic acid morbillivirus sequences attributed as porcine. The specification does not clearly allow persons of ordinary skill in the art to recognize that the inventors invented what is claimed. The claims do not meet the written description provision of 35 U.S.C. 112, first paragraph.
Claims 1-6 and 8 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 enablement requirement. The claim(s) contains 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.
While the nucleic acid of instant claim 1 is an isolated molecule, the nucleic acid, vector, and cell in claims 2-6 and 8 encompass 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. Support for transgenes integrated into the host chromosome within a host is supported in the instant published disclosure, USPgPub 2024/0139306, in at least paragraphs [0064, 0120], referring to transgenic organisms; [0074], i.e., “The nucleic acid can be introduced, for example, on an expression vector having signals capable of expressing the protein encoded by the introduced nucleic acid or the nucleic acid can be integrated into the host cell chromosome,”; paragraphs [0122]: “In addition, when genes critical to the viral life cycle are deleted (e.g., the E2b genes), a further crippling of Ad to replicate or express other viral gene proteins occurs. This will decrease immune recognition of virally infected cells, and allows for extended durations of foreign transgene expression,”; and paragraphs [0148-0150], regarding expression level peaks attributed to materials required for extended replication in the cell cycle.
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 et Al., 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 et al., Journal of Biotechnology, Vol. 34, Pg. 269- 287, 1994, abstract only). Furthermore, transgenic animals are regarded to have within their cells, cellular mechanisms that prevent expression of the transgene, such as methylation or deletion from the genome (Kappell et al., Current Opinions in Biotechnology, Vol. 3, Pg. 548-553, 1992). Houdebine (Comparative Immunology, Microbiology, and Infectious Diseases, Vol. 32, Pg. 107-121, 2009) 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 (Pg. 116, Paragraph, second). Therefore, undue experimentation is required to make and use a transgene and transgenic animal to produce the porcine morbillivirus and fragments of the instant claims.
There is no discussion, data, or working example provided in the instant disclosure for transgenic expression of the scope of nucleic acids and fragments thereof, encompassed by the instant claims. The skilled artisan would not predict success expressing the instant nucleic acids, or fragments thereof, as transgenes. Abdullah et al. (Journal of Virology. 2018; 92 (23): 10.1128/jvi.01248-18) describe single amino acid changes and immune cell receptors of morbilliviruses that contribute to disease resistance and conversely, increased virulence in zoonotic hosts, including humans. Abdullah et al. teach mice expressing human SLAM (a key entry receptor that immune cells in the upper respiratory tract are the first to become infected), do not manifest natural human-specific measles infection when challenged, see the paragraph above Figure 10. There is no indication in the instant disclosure that any cell encompassed by the instant claims would be susceptible or adequately express the porcine morbillivirus genome or any nucleic acid fragments thereof.
Examples in the literature aptly demonstrate that even closely related species carrying the same transgene construct can exhibit widely varying phenotypes. Mullins et al. (1993, Hypertension, Vol. 22, No. 4, pp. 630-633) state 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 (1990, Nature, Vol. 344, 541-544) produced outbred Sprague-Dawley x WKY rats with hypertension caused by expression of a mouse Ren-2 renin transgene. Hammer (1990, Cell, Vol. 63, 1099- 1112) 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, 1989, EMBO J., Vol. 8, pages 4065-4072). 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. For all these reasons, transgenes and hosts comprising 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, encompassing a transgene and cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation by the public to generate and use the invention. Applicants can obviate the instant rejection by amending the claim to recite the term "isolated" before the recitation, "nucleic construct” in claim 2, “vector” in claim 3, “cell" in claim 4, and “porcine morbillivirus epitope” in claim 8, and by amending claim 6 to specify that the method is not conducted in a transgenic animal. Applicant may consider using purified in such claims if 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 instant disclosure, and the absence of working examples, it is determined that an undue quantity of experimentation would be required to make and use the nucleic acids claimed as transgenes and expression in a transgenic animal.
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)(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.
Claims 1 and 8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by:
nucleic acid alignment encoding amino acid SEQ ID NO: 45 with GenEmbl database accession no: KC802221 by Verburgh et al Jul-2013; or
nucleic acid alignment encoding amino acid SEQ ID NO: 48 with GenEmbl database accession no: AY964108 by Pardo et al Mar-2005; or,
nucleic acid alignment encoding amino acid SEQ ID NO: 49 with GenEmbl database accession no: KF835416 by Espinal et al 2014.
GenEmbl database accession no: KC802221 by Verburgh et al Jul-2013, shares 83.1% identity with a nucleic acid sequence encoding SEQ ID NO: 45;
Or
GenEmbl database accession no: AY964108 by Pardo et al Mar-2005, shares 85.3% identity with a nucleic acid sequence encoding SEQ ID NO: 48;
Or
GenEmbl database accession no: KF835416 by Espinal et al 2014 shares 62.5% identity with a nucleic acid sequence encoding SEQ ID NO: 49.
Each sequence alignment, in the alternative, possess multiple stretches of nucleic acids encoding amino acid sequences having 100% identity to at least 5 and more contiguous amino acids of SEQ ID NOs: 45, 48, or 49, anticipating claim 1 and an epitope encoded by any one of the nucleic acid sequences of claim 8. The intended use recited in claim 8 as an immunotherapeutic is not afforded patentable weight since the structure required does not require the preamble for completeness.
Paragraph [0086] of the instant published disclosure (USPgPub 2024/0139306) states that “a nucleotide sequence encoding the amino acid sequence of porcine morbillivirus nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, hemagglutinin protein, and/or large protein”, recited in claim 1, encompasses partial sequences of PoMV polypeptides. Therefore, the sequence alignments provided anticipate this portion of claim 1 as well.
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.
Claims 2-6 are rejected under 35 U.S.C. 103 as being unpatentable over each of the nucleic acid sequence alignments in the alternative listed supra and Hummel et al. (Journal of Clinical Microbiology. Nov. 1992; 30 (11): 2874-2880).
See each of the nucleic acid sequence alignments in the alternative listed supra. None of the alignments discuss the nucleotide sequence linked to a promoter comprised by a baculovirus vector expressed in a host cell, as required in claims 2-5 or a method of producing a morbillivirus by transfecting a cell with the vector, allowing replication in the host cell, and harvesting the morbillivirus from the medium or culture, as required in claim 6.
Hummel et al. teach expressing a measles virus nucleoprotein nucleic acid from a polyhedrin promoter in a baculovirus vector, which is transfected and cultured in Sf9 cells prior purification of the virus. See the abstract and “Recombinant virus construction and purification” under the Materials and Methods and Discussion sections.
One of ordinary skill in the art prior art would have been motivated to have expressed any one of the alternative morbillivirus nucleic acids in the alignments provided in the method of Hummel et al. to produce high titers of virus, see the Introduction. One of ordinary skill in the art prior art would have had a reasonable expectation of success to have expressed any one of the alternative morbillivirus nucleic acids in the alignments provided in the method of Hummel et al. because expressing morbillivirus proteins in a baculovirus system has been accomplished for over three decades, i.e., 1992, as evidenced by Hummel et al.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Arruda et al. (Emerging Infectious Diseases. July 2021; 27 (7): 1858-1866, the inventor’s work), describes a novel morbillivirus attributing to fetal death of porcine subjects.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHANON A FOLEY whose telephone number is (571)272-0898. The examiner can normally be reached M-F, generally 5:30 AM-5 PM, flexible.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at 571-270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Shanon A. Foley/Primary Examiner, Art Unit 1671