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 .
The response and amendment to the claims filed 10-3-2024 has been entered into the record.
Status of Claims
Claims 1, 5, 7, 11, 13, 14, 18, 19, 21-29, 31-38, 44, 45, 54, 58-61, 66, 81 and 88 are pending.
Election/Restrictions
Applicant’s election of Group I and species of: SIV gage protein, RhCMVIL-10, internal ribosome entry site (IRES) comprising an avian encephalomyelitis virus IRES without traverse in the reply filed on 10-3-2024 is acknowledged.
Claims 1, 7, 11, 13, 14, 18, 19, 20, 22, 23, 24, 25, 31-35, 44, 45, 54, 60 and 88 are under examination.
Claims 58, 59, 61, 66 and 81 are withdrawn as drawn to non-elected inventions. Claims 26-29 and 36-38 are withdrawn from consideration as drawn to non-elected species.
Information Disclosure Statement
The information disclosure statements have been considered. Initialed copies are enclosed.
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.
Claim 31, claims dependent thereon (32-35) and 88 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
As to claim 31, the claims states that the protein having IL-10-like activity is a heterologous protein, but does not state what it is heterologous to ? While the specification teaches at paragraph [0055] an apparent definition of “heterologous protein having IL-10 activity, the regulatory sequences for the sequence for which it is heterologous to are not present in claim 1 from which claim 31 depends. Dependent claims 32-35 do not resolve this issue and as such are likewise indefinite. As such, the meaning of heterologous in context cannot be ascertained by the skilled artisan.
As to claim 88, the phrase “the cell” lacks antecedent basis in the claims it depends on and as such is per se indefinite.
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, 5, 7, 13, 21-24, 31-33, 44, 45 and 60 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim et al (WO 98/17799).
As to claims 1, 31, 32 and 33, Kim et al discloses a system for expressing an antigen and a protein having interleukin-10 activity for delivering foreign antigens and live attenuated vaccines. Pharmaceutical compositions comprising nucleic acid molecules that encode IL-10 and IL-10-like proteins are disclosed (see abstract; page 2, lines 21-32). Kim et al teach polynucleotides encoding (IL-10)-like activity in a cell, the system comprising a recombinant polynucleotide comprising a nucleic acid sequence encoding the antigen and a recombinant polynucleotide comprising a nucleic acid sequence encoding the protein having IL-10-like activity. Kim et al teach that the present invention relates to a plasmid which comprises nucleotide sequence(s) that encode one or more of human IL-10 operably linked to regulatory elements necessary for expression in eukaryotic cells and a nucleotide sequence that encodes an immunogenic target antigen operably linked to regulatory elements necessary for expression in eukaryotic cells at page. 6, lines. 17-24. Kim et al teach genetic constructs operably lined to regulatory elements including promoters, initiation codons, stop codons and a polyadenylation signal. Enhancer elements may also be included. Exemplified regulatory elements such promoters, polyadenylation signals, enhancers etc. are exemplified at pages 33-36. Kim et al teach that the nucleic acids can be administered together with facilitating agents. Kim et al teach that the invention provides for improved methods and compositions for vaccination, particular DNA vaccination in which DNA encodes a target immunogen is administer to the individual which is co-delivered with DAN that encodes immunomodulating proteins such that the expression provides for the direction of the immune response (see page 26, last paragraph). The methods of DNA administration can be as either a single nucleic acid molecule that comprises a sequence that encodes a target protein and a sequence that encodes the immunomodulating proteins or a composition having two nucleic acid molecules one having the target protein and the other the immunomodulating protein. As to claim 13, the nucleic acid may be provided as plasmid DNA , recombinant vectors or as part of the genetic material provided in an attenuated vaccine (see page 30, lines 8-23). As to claim 5, Kim et al discloses the system of claim 1, wherein the antigen and the protein having IL-10-like activity are expressed in the same cell. Kim et al teaches that the present invention relates to a plasmid which comprises nucleotide sequence(s) that encode one or more of human proteins with IL-10 like activity and including IL-10 per se operably linked to regulatory elements necessary for expression in eukaryotic cells and a nucleotide sequence that encodes an immunogenic target antigen operably linked to regulatory elements necessary for expression in eukaryotic cells, page 6, lines. 17-24.
As to claims 21, 22, 23 and 24, Kim et al discloses the system of claim 1, where compositions and methods are provided which prophylactically and/or therapeutically immunize an individual against a pathogen (i.e. the instant infectious disease antigen) or abnormal, disease-related cell. The genetic material that encodes a target protein, i.e. a peptide or protein that shares at least an epitope with an immunogenic protein found on the pathogen or cells to be targeted, and genetic material that encodes an immunomodulating protein. The genetic material is expressed by the individual's cells and serves as an immunogenic target against which an immune response is elicited see page 30, lines 23-35. Kim et al teach pathogens such as viruses, prokaroyte and pathogenic eukaroytic organisms can be targeted. In preferred embodiments the methods o immunizing an individual against a pathogen are directed against HIV, HTLV or HBV. See page 40 line 25- page 41, line 35 and targets are exemplified in Tables 1 and 2. As to Claim 24, Kim et al discloses the system of claim 23, wherein the infectious disease antigen comprises an HIV or SIV group-specific antigen (gag) protein (In some preferred embodiments, the methods of immunizing an individual against a pathogen are directed against HIV using a gag protein where DNA vaccine constructs expressing HIV-1 envelope protein (pCEnv) and gag/pol protein (pCGag/Pol) were prepared using standard techniques and readily available starting materials. The genes for human cytokines including IL-10,were cloned into the pCDNA3 expression vector using standard techniques and readily available starting materials, see page 82, lines 24-31.
As to claims 5 and 7, Kim et al discloses the system of claim 1, wherein the recombinant polynucleotide comprising the nucleic acid sequence encoding the antigen and/or the recombinant polynucleotide comprising the nucleic acid sequence encoding the protein having IL-10-like activity further comprise one or more nucleic acid sequences that encode a regulatory sequence. Kim et al teach that the DNA or RNA sequences encoding the target protein and an immunomodulating protein are linked to regulatory elements necessary for expression in the cells of the individual. Regulatory elements for DNA expression include a promoter, a polyadenylation signal and other regions such as Kozak regions or enhancers (see page 32, lines 4-9 and pages 33-34). Kim et al discloses the system of claim 5, wherein the regulatory sequence controls expression of the antigen and/or the protein having IL-10-like activity (The DNA or RNA sequences encoding the target protein and an immunomodulating protein are linked to regulatory elements necessary for expression in the cells of the individual. Regulatory elements for DNA expression include at least a promoter and a polyadenylation signal. Kim et al a composition which comprises a plurality of plasmids which includes two plasmids: a first plasmid which comprises nucleotide sequence(s) that encode one or more of human... IL-10 protein operably linked to regulatory elements necessary for expression in eukaryotic cells and a second plasmid which comprises a nucleotide sequence that encodes an immunogenic target antigen operably linked to regulatory elements necessary for expression in eukaryotic cells (see page 7, lines 11-20).
As to claim 13, Kim et al discloses the system of claim 1, wherein the recombinant polynucleotide comprising the nucleic acid sequence encoding the antigen and the recombinant polynucleotide comprising the nucleic acid sequence encoding the • protein having IL-10-like activity are the same recombinant polynucleotide (see page 6, lines 17-24). Kim et al teach that the antigen and the protein having IL-10-like - activity are expressed under the control of two different promoters at page 6, lines 17-24.
As to claims 44 and 45, Kim et al discloses the system of claim 1, wherein the recombinant polynucleotide comprising the nucleic acid sequence encoding the antigen and/or the recombinant polynucleotide comprising the nucleic acid sequence encoding the protein having IL-10-like activity are present within a viral vector and specifically teach contemplated are other nucleic acid based vectors such as recombinant viruses and exemplify recombinant vaccina virus vectors, adenovirus virus vectors and retroviral vectors at page 47, lines 6-20.
As to claim 60, Kim et al discloses that their present invention relates to a pharmaceutical composition which comprises a recombinant vector which comprises nucleotide sequence (s) that encode one or more of human IL-10 operably linked to regulatory elements necessary for expression in eukaryotic cells and a pharmaceutically acceptable carrier or diluent, at page 10, lines 25-31.
For the foregoing reasons Kim et al anticipate the instantly claimed invention.
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 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.
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 7, 14, 18 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (WO 98/17799; of record) in view of Chaplin et al (WO 2018/083111; of record).
The teachings of Kim et al are set forth supra. As to claims 7 and 14, Kim et al discloses the system of claim 5 wherein the recombinant polynucleotide comprises (a) the nucleic acid sequence encoding the antigen; and (c) the nucleic acid sequence encoding the protein having IL-10-like activity, but Kim et al fails to explicitly disclose (b) a nucleic acid sequence encoding an IRES. As to Claim 18, Kim et al discloses the system of claim 13. Kim et al fails to explicitly disclose wherein the antigen and the protein having IL-10-like activity are expressed as a single protein.
Chaplin et al teaches an IRES situated 3' to an antigen encoding sequence and 5' to an IL-10 encoding sequence (The chronology/sequence of expressed proteins and IRES/2A elements herein may therefore be as follows: (i) Antigen, (ii) FMDV 2A, (iii) TGF beta 1, (iv) IRES, (v) IL-10, (vi) P 2A, and (vii) IL-2, at page 10, lines. 1-3). Chaplin et al teaches an antigen and IL-10 expressed as a single protein separated by self-cleaving peptides such as 2A (The chronology/sequence of expressed proteins and IRES/2A elements herein may therefore be as follows: (i) Antigen, (ii) FMDV 2A, (iii) TGF beta 1, (iv) IRES, (v) IL-10, (vi) P 2A, and (vii) IL-2, at page 10, lines. 1-3.
As to claims 7 and14, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to modify the single polynucleotide of Kim et al with the teaching of Novo Nordisk for the purpose of using a sequence element to express two polypeptides in a single reading frame.
As to claim 18, it would have been obvious to one of ordinary skill in the art at the time of the invention to modify Kim et al with the teaching of Chaplin et al for the purpose of using a single reading frame to express a plurality of proteins that can be separated by self-cleaving peptides to optimize expression in mammalian cells.
As to Claim 19, it would have been prima facie obvious to have modified Kim et al as set forth for the system of claim 18. Kim et al fails to explicitly disclose wherein the single protein is a self-cleaving protein, and wherein self-cleavage of the single protein yields the antigen and the protein having IL-10-like activity as separate proteins. It would have been further prima facie obvious to one of ordinary skill in the art at the time of the invention to modify the single nucleotide embodiment of Kim et al as modified for claim 18 supra with the teaching of the use of self cleaving peptides of Chaplin et al for the purpose of using a single reading frame to express a plurality of proteins that can be separated by self-cleaving peptides to optimize expression in mammalian cells.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (WO 98/17799) and Chaplin et al (WO 2018/083111; of record) as applied to claims 7, 14, 18 and 19 above and further in view of Barnett et al (WO 2005/037840) and Pei et al (WO 2017/008154) .
The combination of Kim et al and Chaplin et al is set forth supra but does not teach that the IRES is an avian encephalomyelitis virus IRES.
As to Claim 11, Kim et al discloses the system of claim 7. Kim et al fails to explicitly disclose wherein the IRES is an avian encephalomyelitis virus IRES.
Barnett et al teach that expression cassette delivery vectors can be generated such that more than one gene of interest is expressed. This may be accomplished by the use of di-or oligo-cistronic cassettes or thorough the use of Internal ribosome entry sites (IRES) (page 64, lines 3-7).
Pei et al teach and IRES from a Canadian isolate of avian encephalomyelitis (AEV-IRES; SEQ ID NO:41) at paragraph [00129].
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention was filed to modify the combination of Kim et al and Chaplin et al by substituting the AEV-IRES of Pei et al for the IRES of Kim et al and Chalpin et al as combined because the use of IRES to drive expression of one or more genes of interest was known to the art and provide for in vaccine vectors of the art as taught by Barnett et al. The substitution of one IRES for another is prima facie obvious as they both have the same function as use of providing for expression of multiple proteins in a multi-cistronic vector.
Claims 34 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (WO 98/17799; of record) in view of Schall et al. (US 2002/0197234; of record).
The teachings of Kim et al are set forth supra. Kim et al discloses the system of claim 31. Kim et al fails to explicitly disclose wherein the viral protein having IL-10-like activity is a cytomegalovirus (CMV) protein having IL-10-like activity and rhesus macaque CMV IL-10.
Schall teaches human CMV IL-10. Schall teaches pharmaceutical compositions and prophylactic and therapeutic methods of treatment for immune disorders using rhesus or human CMV IL-10 interchangeably (see Abstract). Cytokines can be used to augment a patient's immune response by administering rhesus CMV IL-10 or human CMV IL-10 (see paragraph [0124]).
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing the invention to modify Kim et al with the teaching of Schall by substituting the rhesus CMV IL-10 for the human IL-10 disclosed by Kim et al for the purpose of eliciting an immune response in a subject according to Kim et al and Schall as both IL-10 molecules have the desired properties of boosting an immune response to an antigen.
Claim 54 is rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (WO 98/17799) in view of Kishimoto (US 2016/0067228; of record).
The teachings of Kim et al are set forth supra. As to claim 54, Kim et al discloses the system of claim 1. Kim et al fails to explicitly disclose wherein the protein having IL-10-like activity is one to which a host does not have pre-existing immunity.
Kishimoto teaches ensuring a subject does not have pre-existing immunity to viral vectors and IL-1O therapy. In one embodiment, the subject does not have pre-existing immunity against the viral transfer vector, Para. (0004); In one embodiment of any one of the methods provided, the level of pre-existing immunity is to an antigen of a protein transgene expression product of the viral transfer vector, Para. (0015); In one embodiment of any one of the methods provided herein, when the transgene is a gene therapy transgene, the gene therapy transgene encodes a therapeutic protein. In one embodiment of any one of the methods provided herein, the therapeutic protein is a/an... cytokine, Para. (0040); Examples of cytokines include... IL-10, Para. (0152)).
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing the invention to modify Kim et al with the teachings of Kishimoto for the purpose of ensuring a subject does not have existing immunity against IL-10 or the viral vector that will exacerbate an unwanted immune response in the subject and reduce the efficacy of therapy.
Claim 88 is rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (WO 98/17799; of record) in view of Jones et al. (US 2018/0187211; of record).
Kim et al is set forth supra. Kim et al fails to explicitly disclose wherein the CMV viral vector contains a mutation that increase tropism for “the” cell.
Jones teaches viral vectors such as CMVs having increased tropism by introduction of a CD154 coding sequence (To overcome these challenges, the present invention provides combination multi-targeted vaccines, immunotherapies and methods for enhanced therapeutic response to complex diseases such as infectious diseases and cancers, Para. (0011); Suitable viral vectors that can be used with the methods and compositions of the present disclosure include but are not limited to... adenoviruses, ... Cytomegalovirus, Para. (0148); In some applications the recombinant adenovirus vector is altered to increase tropism to a specific organ in a mammal, Para. [0160); Modification of capsid proteins can be used as a strategy to optimize infection of DC by Ad vectors, as well as enhancing functional maturation, for example using the CD40L receptor as a viral vector receptor, Para. (0203]).
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to modify the CMV viral vector contemplated by Kim et al with the teaching of Jones by mutating the CMV viral vector to increase tropism for a cell for the purpose of maximizing therapeutic efficacy of a vaccine by enhancing vector tropism to deliver antigen-encoding and IL-10-encoding constructs to target cells.
Free of Prior Art
Claim 25 is free of the prior art inasmuch as the art does not suggest or fairly teach the specific sequence claimed.
Conclusion
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/Patricia Duffy/Primary Examiner, Art Unit 1645