DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-15 are pending in the application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/102023 has been considered by the examiner.
Specification
The use of the term “Lipofectamine LTX” and “OPTI-MEM,” which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears 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.
Claim Objections
The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
Since there are two claim 3, the second claim 3 is considered as misnumbered and has been renumbered to claim 4. Claims following newly renumbered claim 4 has been renumbered as 5-16 accordingly.
Claim 11-16 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend on another multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims 11-16 have not been further treated on the merits.
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 2 is 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.
Regarding claim 2, the term “merely contain” renders the claim indefinite because it is unclear whether it means “consists” or “comprising” for the exogenous genes.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5 and 10 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 5 and 10 depend on itself, thus fails to further limit the subject matter of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Note: the dependency of both claims have been changed to claim 5 and 10 because the originally numbered claims 4 and 9 depends on itself.
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, 8-10 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.
The written description requirement is set forth by 35 U.S.C. 112, first paragraph which states that the: “specification shall contain a written description of the invention. . .[emphasis added].” The written description requirement has been well established and characterized in the case law. A specification must convey to one of skill in the art that “as of the filing date sought, [the inventor] was in possession of the invention.” See Vas Cath v. Mahurkar 935 F.2d 1555, 1560 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). Applicant may show that he is in “possession” of the invention claimed by describing the invention with all of its claimed limitations “by such descriptive means as words, structures, figures, diagrams, formulas, etc., that fully set forth the claimed invention.” See Lockwood v. American Airlines Inc. 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997).
In analyzing whether the written description requirement is met, it is first determined whether a representative number of species have been described by their complete structure. Next, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics.
Claim 1 recites A) African swine fever virus derived p72 variants formed by substitution, deletion or addition of one or more amino acid residues in the amino acid sequence of the capsid protein p72 and have the function of the capsid protein p72; B) African swine fever virus derived B602L variants formed by substitution, deletion or addition of one or more amino acid residues in the amino acid sequence of the accessory protein B602L and have the function of prompting the accurate expression and folding of the capsid protein p72 or variants thereof; and C) African swine fever derived CD2V variants formed by substitution, deletion or addition of one or more amino acid residues in the amino acid sequence of the exterior envelope protein CD2V and have the function of the exterior envelope protein CD2V. Claim 6 recites an African swine fever derived p49 variants formed by substitution, deletion or addition of one or more amino acid residues in the amino acid sequence of the capsid protein p49 and have the function of the capsid protein p49. Claim 3 recites sequences having 90% identity with SEQ ID NO: 1, 2 and 3. The claimed p72, B602L, CD2V and p49 encompasses a large genus of polypeptides that comprises a large amount of mutations or combination of mutations thereof, including not only substitution, but also addition and deletion in or more amino acid residues encoding said protein, which result in polypeptide of varying lengths and structure. The specification teaches codon optimized p72, B602L and CD2V isolated from Georgia 2007/1 strain African swine fever virus encoded by SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3 were expressed by a recombinant pseudorabies virus and administered to Balb/c mice. The specification teaches the serum of mice produces antibodies that can bind to p72 and CD2V. However, the specification does not teach any “variants” of said p72, p49, B602L and CD2V with substitution, addition and/or deletion of one or more amino acids that retains the function of the wild type p72, p49, B602L and CD2V as claimed. The specification does not teach any sequence with 90% homology with SEQ ID NO: 1, 2 and 3 that has the same function.
The knowledge in prior art does not make up such deficiency. In a review article, Chen et al (Viruses 2024, Vol. 16, no. 913, pages 1-18) teach ASFV is a complex double stranded DNA virus with genome sizes varying from 170 to 195 kilobase pairs, and comprises three distinct regions. Chen et al. teach the left and right variable region (LVR and RVR) contribute to genetic diversity with B646L (encodes p72) and EP402R (encodes CD2v) being used to make classification (page 2nd paragraph, and Figure 1 and legend). Chen et al. teach the changes in viral genome caused by insertions and deletions may severely affect the protein’s function, leading to loss of the entire functional protein, with major implications for viral adaptation and evolution (page 3, 4-6). Based on such teaching, whether “variants” formed by substitution, insertion and/or deletion of one or more amino acid residue within the amino acid sequence encoding p72, p49, B602L and CD2V may still retain the function of wild type amino acid sequence would be unpredictable.
In view of the large genus of “variant” claimed in claim 1, claim 6 and dependent claims thereof (2-7, and 8-10), the specification does not describe a representative number of species by their complete structure, nor other identifying characteristics for the claimed function. A skilled in the art thus cannot immediately envision the structure of the variants based on the function of said proteins. Therefore, the specification fails to describe the claimed genus of variants sufficiently to reasonably convey a skilled in the art that the inventor had possession of the invention at the time the application was filed.
Claims 9 and 10 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (a) the nature of the invention; (b) the breadth of the claims; (c) the state of the prior art; (d) the amount of direction provided by the inventor; (e) the existence of working examples; (f) the relative skill of those in the art; (g) whether the quantity of experimentation needed to make or use the invention based on the content of the disclosure is "undue"; and (h) the level of predictability in the art (MPEP 2164.01 (a)).
Nature of the invention
Claims 9 and 10 are drawn to an African swine fever vaccine comprises the recombinant PRV that comprises nucleotide A, B and C, which encodes p72, B602L, and CD2V, and variants thereof.
The teaching from the specification and the presence of working examples
The specification teaches the recombinant PRV vaccine is used for treating and preventing ASF (paragraph 0071]). The specification teaches treating or preventing involves the administration of animals in need with effective dosage to treat animals already infected with AFSV and show clinical syndromes caused by ASFV, or before infection by ASFV to decrease the severe degree of clinic syndrome or morbidity of ASFV (paragraph [0072]-[0073]). The specification teach codon optimized p72, B602L and CD2V isolated from Georgia 2007/1 strain African swine fever virus encoded by SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3 were expressed by a recombinant pseudorabies virus, wherein the genes encoding p72, B602L and CD2V are inserted into non-essential replication region of PRV TK coding region and gG coding region. The specification teaches the recombinant PRV were administered into Balbc mice, and the serum of mice produces antibodies that can bind to p72 and CD2V. However, the specification does not teach whether administering the recombinant PRV encoding p72, B602L and CD2V can protect an animal such as a pig from infection from ASFV and develop African swine fever or whether it can ameliorate symptoms of ASF in an animal already infected. As such, whether the claimed recombinant PRV can be a ASF vaccine is unpredictable based on the teaching from the specification.
The teaching from prior art and the level of unpredictability in the art
In a review article, Chen et al (Viruses 2024, Vol. 16, no. 913, pages 1-18) teach ASFV is a complex double stranded DNA virus with genome sizes varying from 170 to 195 kilobase pairs, and comprises three distinct regions. Chen et al. teach the left and right variable region (LVR and RVR) contribute to genetic diversity with B646L (encodes p72) and EP402R (encodes CD2v) being used to make classification (page 2nd paragraph, and Figure 1 and legend). Chen et al. teach the strain specificity of the virulence-associated genes in ASFV, resulting from its complex genomic structure, is a major impediment to vaccine research and development and a formidable obstacle to effective ASF control (page 2, 2nd paragraph, bottom lines). Chen et al. teach low fidelity DNA repair pathway and the frequency of viral recombination enhances virus’ genetic diversity and its ability to resist host immune responses and therapeutic interventions (page 3, 1st and 2nd paragraph). Based on such teaching, whether a recombinant PRV encoding p72, B602L and CD2V may be used as a vaccine for treating and/or preventing ASF is unpredictable.
The amount of experimentation required
Due to lack of teaching from instant specification, and the complexity of ASFV genome that contributes to significant obstacle for develop an effective vaccine as discussed in the current state of art, a skilled artisan would need to engage in undue experimentation to use the claimed recombinant PRV as vaccine for protecting and/or treating ASF in an animal. Therefore, the claimed invention of claims 9 and 10 is not enabled by the instant specification.
Claim Rejections - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 2, 4-10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ren et al (CN110269932A), in view of Chowdhury (WO2017/10636).
Ren et al. teach an immunogenic composition which comprises a first construct, a second construct and a third construct, wherein the first construct encodes ASFV genes including B602L and CD2V, the second construct including p72 (summary of the invention, 1st paragraph). Ren et al. teach the constructs are based on viral vectors including retrovirus, adenovirus, poxvirus, herpes virus, measle virus, foam virus, vesicular stomatitis virus and adeno-associated virus (virus section).
However, although pseudorabies virus is a herpes virus, Ren does not specifically teach the viral vector is from pseudorabies virus (PRV).
Chowdhury teaches PRV vector expressing heterologous polypeptides (title). Chowdhury teaches a viral vector comprising a pseudorabies virus with at least two genomic deletions that eliminate glycoprotein E (gE) and thymidine kinase (TK), and glycoprotein G (gG) expression (abstract). Chowdhury teaches the viral vector can include one or more heterologous nucleic acid segments, and gives example of classical swine fever viral (CSFV) or porcine circovirus 2 (PCV2) polypeptides (abstract). Chowdhury teaches said PRV vector is used to immunizing an animal, particularly a swine, against one or more disease caused by a virus (page 12, 3rd paragraph).
It would have been obvious to an ordinary skilled in the art that recombinant PRV would be a suitable vector for encoding ASFV antigenic protein p72, B602L and CD2V based on combined teaching from Chowdhury and Ren et al. The ordinary skilled in the art would be motivated to use rPRV when trying to developing an ASFV vaccine because Chowdhury teaches rPRV is a suitable vector for immunizing an animal, particularly a swine, and give example of expressing CSFV and PCV2 polypeptides to develop a vaccine. The ordinary skilled in the art would have reasonable expectation of success to isolate nucleotide encoding p72, B602L and CD2V from ASFV strain and insert it into viral genome of PRV’s nonessential genes following combined teaching from Ren and Chowdhury. Therefore, the claimed invention of claims 1 and 2 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claim 4-5, Chowdhury teaches the virus is suitable for replicating in swine kidney cells, SK-RST, which meets the limitation of a mammalian cell (page 26, 1st paragraph).
Regarding claim 6, Ren further teaches expressing p49 derived from ASFV (abstract).
Regarding claim 7, Chowdhury teaches rPRV with deletion in TK, gE and gG (abstract).
Regarding claim 8, the claimed method comprises deleting coding region of TK gene with codon optimized p72, inserting a codon optimized B602L into the capsid protein p72, and substituting gG from rPRV coding region with codon optimized Cd2V, and transfecting the rPRV into hamster kidney cells for expressing said heterologous proteins. Chowdhury already taught deletion strains of rPRV at TK and gG and inserting heterologous PCV cap chimeric gene (page 26, 1st and 3rd paragraph). It would have been obvious to an ordinary skilled in the art insert codon optimized p72, B02L and CD2V into the already deleted locus in rPRV taught by Chowdhury and expressing them in kidney cells. Substituting one antigenic polypeptide with another antigenic polypeptide for same purpose would have been obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claims 9 and 10, the combined teaching from Ren and Chowdhury renders obvious of the rPRV components of the claimed vaccine.
SEQ ID NO:1, 2 and 3 are free from prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/ Primary Examiner, Art Unit 1637
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