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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the abstract includes the legal phraseology “comprises”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim 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 8-13 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 8 recites the limitation "the hydrophilic or hydrophobic molecule" in lines 1-2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claims 9-13 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 since they depend directly on rejected dependent claim 8 and therefore, contain the same deficiencies.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-4, 8-9, 14, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tiwari et al. U.S. Publication No. (2015/0017202 A1).
With respect to claim 1, Tiwari et al. discloses a method for identification of an adjuvant and adjuvant combination, comprising: using an adjuvant or adjuvant combinations to treat at least one type of antigen-presenting cells and measuring amount of at least one cytokine produced by the at least one type of antigen presenting cells (Abstract "The invention provides novel immunological adjuvants and methods for identification of such adjuvants. The invention further provides methods and compositions for eliciting an immune response to an immunogen using the novel adjuvants The immunogen can be derived from a virus, a cancer, or a diseased cell. The elicited immune response can be cellular, humoral, or both."; para [0007]-[0008] "a method of identifying an immunological adjuvant. testing the compound for activation of NF-KB, wherein activation of NF-kB indicates that the compound is an immunological adjuvant. The immunological adjuvants of the invention activate NF-kB activation of NF-kB is indicated by secretion of one or more inflammatory cytokines from an antigen presenting cell (APC), such as, but not limited to, a macrophage or a dendritic cell. In an embodiment of the invention, activation of NF-kB is indicated by expression of a reporter gene under NF-kB control").
With respect to claim 2, Tiwari et al. discloses the adjuvant comprises a hydrophobic molecule (Abstract "The adjuvants can be employed with any suitable immunogen, including proteins, peptides, lipids, and carbohydrates."; para [0044] "Immunogenic compositions of the invention may further comprise coadjuvants, which generally promote nonspecific immune responses liposomes").
With respect to claim 3, Tiwari et al. discloses at least one cytokine has the property to stimulate at least one type of antigen-presenting cells (para [0008] "The immunological adjuvants of the invention activate NF-kB. In an embodiment of the invention, activation of NF-kB is indicated by nuclear localization. In another embodiment of the invention, activation of NF-kB is indicated by secretion of one or more inflammatory cytokines from an antigen presenting cell (APC), such as, but not limited to, a macrophage or a dendritic cell. In an embodiment of the invention, activation of NF-KB is indicated by expression of a reporter gene under NF-kB control").
With respect to claim 4, Tiwari et al. discloses the antigen- presenting cell is a dendritic cell (para [0008]).
With respect to claim 8, Tiwari et al. discloses the hydrophilic or hydrophobic molecule is capable of stimulating expression of a type I interferon or an inflammatory cytokine (para [0008] "NF-kB"; para [0031]).
With respect to claim 9, Tiwari et al. discloses the hydrophilic or hydrophobic molecule is a Toll-like receptor ligand or agonist (para [0005] "Another class of adjuvants which is gaining interest is toll-like receptor (TLR) agonists."; para [0007] "In an embodiment of the invention, the toll-like receptor is TLR-4, whose function involves the adaptor molecule MD-2 and CD 14").
With respect to claim 14, Tiwari et al. discloses the cytokine can stimulate maturation of the antigen-presenting cells (para [0031] "According to the invention, adjuvant peptides induce secretion of proinflammatory cytokines and related proteins. Thus, adjuvant peptides of the invention are identified by induction of secretion of tumor necrosis factor (TNF; TNF-a, cachexin)"; note, TNF-a can stimulate maturation of the antigen-presenting cells as evidenced by instant application claim 16).
With respect to claim 16, Tiwari et al. discloses the cytokine is tumor necrosis factor-alpha (para [0031]).
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.
Claim(s) 5-7 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Tiwari et al. as applied to claims 4 and 14 above and further in view of Spencer et al. U.S. Publication No. (2018/0305667 A1).
With respect to claim 5, Tiwari et al. substantially discloses the invention as claimed except the dendritic cell is derived from bone marrow cells. Note: Tiwari et al. discloses the use of dendritic cell in composition, see para [0008].
Spencer et al. however, teaches dendritic cells derived from bone marrow cells can be used in conjunction with adjuvants to stimulate an immune response (para [0103] "Secreted or soluble molecules, such as for example, cytokines and adjuvants, may also aid or enhance the immune response against an antigen. Such molecules are well known to one of skill in the art, and various examples are described herein."; para [0108] "The term "dendritic cell" (DC) is an antigen-presenting cell existing in vivo, in vitro, ex vivo, or in a host or subject, or which can be derived from a hematopoietic stem cell or a monocyte. Dendritic cells and their precursors can be isolated from a variety of lymphoid organs, e.g., spleen, lymph nodes, as well as from bone marrow and peripheral blood.").
Given that Tiwari et al. discloses wherein the composition works with dendritic cells, in view of the teachings of Spencer et al., it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to incorporate dendritic cell is derived from bone marrow cells since dendritic cell is an antigen-presenting cell existing in vivo, in vitro, ex vivo, or in a host or subject.
With respect to claim 6, the combination of Tiwari et al./Spencer et al. substantially discloses the invention as claimed. Spencer et al. further teaches the dendritic cell is isolated from peripheral blood or a tissue. Spencer et al. teaches dendritic cells isolated from peripheral blood can be used in conjunction with adjuvants to stimulate an immune response (para [0103]; para [0108]). Since Tiwari et al. discloses the composition works with dendritic cells, it would have been obvious to an artisan of ordinary skill in the art to consider using dendritic cells isolated from peripheral blood as APCs.
Regarding claim 7 the combination of Tiwari et al./Spencer et al. substantially discloses the invention as claimed. Spencer et al. further teaches the dendritic cell is an immortalized cell line. Spencer et al. teaches immortalized dendritic cells can be used in conjunction with adjuvants to stimulate an immune response (para [0103]; para [0108]; para [0392] "2DSC/1 cells represent a rare subset of immortalized DC lines that retain both the immature DC phenotype and the ability to mature following activation signals").
With respect to claim 15, Tiwari et al. substantially discloses the invention as claimed except the cytokine is interferon- beta.
Spencer et al. however teaches inducing an immune response with an adjuvant for use in vaccines, wherein a helpful immune response includes an interferon-beta response (para [0026] "Provided also is a method for inducing a cytotoxic T lymphocyte (CTL) immune response against an antigen, which comprises: contacting a human antigen-presenting cell sensitized with an antigen with: (a) a multimeric molecule having two or more regions that bind to and multimerize native CD40, and (b) an inducible PRR adapter, for example, MyD88, truncated MyD88, or TRIF; whereby a CTL immune response is induced against the antigen. By TRIF is meant the TIR-domain-containing adapter-inducing interferon-beta."; para [0128] "the vaccine is able to provoke an immune response including, but not limited to, the production of antibodies, cytokines and/or other cellular responses").
In view of the teachings of Spencer et al., it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the method of Tiwari et al. by incorporating cytokine is interferon- beta in order to identify adjuvants capable of inducing an interferon-beta response.
Claim(s) 10 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Tiwari et al. as applied to claim 8 above, and further in view of Stephan U.S. Publication No. (2020/0123219 A1).
With respect to 10, Tiwari et al. substantially discloses the invention as claimed except the hydrophilic or hydrophobic molecule is a STING agonist.
Stephan however teaches systems and methods to increase the efficacy of vaccines (Abstract) and [0156] comprising one or more STING agonists are used as a vaccine adjuvant. “STING” is an abbreviation of “stimulator of interferon genes”, which is also known as “endoplasmic reticulum interferon stimulator (ERIS)”, “mediator of IRF3 activation (MITA)”, “MPYS” or “transmembrane protein 173 (TM173)”. STING is a transmembrane receptor protein and is encoded by the gene TMEM173 in human. Activation of STING leads to production of Type I interferons (e.g. IFN-α and IFN-β), via the IRF3 (interferon regulatory factor 3) pathway; and to production of pro-inflammatory cytokines (e.g. TNF-α and IL-Iβ), via the NF-κB pathway and/or the NLRP3 inflammasome [0160] and [0170, DMXAA].
In view of the teachings of Stephan, it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the method of Tiwari et al. by incorporating a hydrophilic or hydrophobic molecule that is a STING agonist as activation of STING leads to production of Type I interferons [0160] of Stephan
With respect to 12, the combination of Tiwari et al./Stephan substantially discloses the invention as claimed. Stephan further teaches the hydrophilic or hydrophobic molecule is selected from a compound library based on its cytokine-stimulating property [0082] and [0160].
With respect to 13, the combination of Tiwari et al./Stephan substantially discloses the invention as claimed. Stephan further teaches the hydrophilic or hydrophobic molecule is an mRNA molecule [0080]-[0083].
Claim(s) 11 is rejected under 35 U.S.C. 103 as being unpatentable over Tiwari et al. as applied to claim 8 above, and further in view of Tor et al. U.S. Publication No. (2021/0101924 A1).
With respect to 11, the combination of Tiwari et al. substantially discloses the invention as claimed except the hydrophilic or hydrophobic molecule is a nucleotide analogue.
Tor et al. however, teaches dinucleotides that are useful as STING agonists, pharmaceutical compositions and vaccines comprising the cyclic dinucleotides, and methods of treating diseases and disorders using the cyclic dinucleotides, pharmaceutical compositions, and vaccines (abstract) comprising nucleic acids containing known nucleotide analogs or modified backbone residues or linkages, which are synthetic, naturally occurring, and non-naturally occurring, which have similar binding properties as the reference nucleic acid, and which are metabolized in a manner similar to the reference nucleotides. Examples of such analogs include, without limitation, phosphodiester derivatives including, e.g., phosphoramidate, phosphorodiamidate, phosphorothioate (also known as phosphothioate having double bonded sulfur replacing oxygen in the phosphate), phosphorodithioate, phosphonocarboxylic acids, phosphonocarboxylates, phosphonoacetic acid, phosphonoformic acid, methyl phosphonate, boron phosphonate, or O-methylphosphoroamidite linkages as well as modifications to the nucleotide bases such as in 5-methyl cytidine or pseudouridine; and peptide nucleic acid backbones and linkages. Other analog nucleic acids include those with positive backbones; non-ionic backbones, modified sugars, and non-ribose backbones (e.g. phosphorodiamidate morpholino oligos or locked nucleic acids (LNA) as known in the art), including those described in U.S. Pat. Nos. 5,235,033 and 5,034,506, and Chapters 6 and 7, ASC Symposium Series 580, Carbohydrate Modifications in Antisense Research, Sanghui & Cook, eds. Nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids. Modifications of the ribose-phosphate backbone may be done for a variety of reasons, e.g., to increase the stability and half-life of such molecules in physiological environments. Mixtures of naturally occurring nucleic acids and analogs can be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made. In embodiments, the internucleotide linkages in DNA are phosphodiester, phosphodiester derivatives, or a combination of both [0032].
In view of the teachings of Tor et al., it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the method of Tiwari et al. by incorporating a hydrophilic or hydrophobic molecule that is a nucleotide analogue which mimics natural nucleotides.
Claim(s) 17-22 are rejected under 35 U.S.C. 103 as being unpatentable over Tiwari et al. as applied to claim 1 above, and further in view of Hoeprich Jr. et al. (WO 2009/143280A2).
With respect to claim 17, Tiwari et al. substantially discloses the invention as claimed except the hydrophilic or hydrophobic molecule can be packaged into a nanometer-size or micrometer-size particle.
Hoeprich Jr. et al. however, teaches wherein vaccines with nanosized lipid components increase potency and therefore reduce costs and increases safety (para [0013]-[0014]; para [0035] "The diameter of the NLPs can be between about 5 and about 50 nanometers, typically ranging between about 10 and about 25 nanometers"; para [00115] "In certain embodiments, an adjuvant and an NLP can also be comprised in a system to immunize an individual. In those embodiments, the system comprises: the immunogenic particle herein described and an adjuvant, the immunogenic particle and the adjuvant to be administered to the individual to immunize such individual."; para [00119] "With respect to commercial vaccine preparation, the binding of immunogens to immunogenic NLPs is expected to both increase the potency of a vaccine antigen (reducing the need to produce so much immunogen, hence reducing costs), and would be expected to reduce the need for addition of a non-specific adjuvant making the vaccine safer since some adjuvants can produce pathogenic immune stimulation and making vaccines less expensive to produce by removing the need for additional adjuvants."). Given that nanosized lipid components are advantageous to adjuvant stimulation in a vaccine, it would have been obvious to an artisan of ordinary skill in the art to consider the nanometer sized particular compositions of LLNS applied to adjuvants tested using Tiwari et al. methods.
With respect to claim 18, the combination of Tiwari et al./ Hoeprich Jr. et al. substantially discloses the invention as claimed. Hoeprich Jr. et al. further teaches the particle is a lipid nanoparticle (para [0011] "The nanolipoprotein particle comprises a scaffold protein, the hydrophilic target molecule attaching an anchor compound, and a functionalized membrane forming lipid attaching an anchor compound substrate and, optionally, a membrane forming lipid.").
With respect to claim 19, the combination of Tiwari et al./ Hoeprich Jr. et al. substantially discloses the invention as claimed. Hoeprich Jr. et al. further teaches the hydrophobic molecule packaged in a particle can stimulate cytokine expression in antigen-presenting cells (para [00114] "In some embodiments, the formation of immunogenic NLPs herein described is amenable to the incorporation of secondary additives such as compounds directed to enhance immune response e.g. non-human lipoproteins, bacterial peptides, DNA (e.g. CpG motifs), chemokines, cytokines").
With respect to claim 20, the combination of Tiwari et al./ Hoeprich Jr. et al. substantially discloses the invention as claimed. Hoeprich Jr. et al. further teaches wherein the hydrophobic molecule packaged in a particle has an equal or greater activity in stimulating cytokine expression in antigen-presenting cells compared to its free form (para [00114]; para [00119]).
With respect to claim 21, the combination of Tiwari et al./ Hoeprich Jr. et al. substantially discloses the invention as claimed. Hoeprich Jr. et al. further teaches wherein the hydrophobic molecule synergizes with a particulate component in stimulating cytokine expression in antigen presenting cells (para [00114]; para [00119]).
With respect to claim 22, the combination of Tiwari et al./ Hoeprich Jr. et al. substantially discloses the invention as claimed. Hoeprich Jr. et al. further teaches wherein the hydrophilic or hydrophobic molecule in the particle has the capacity to promote antigen processing and presentation in antigen presenting cells (para [00115]; para [00125] "Additionally, in several embodiments, the immunogenic particle, methods and systems herein described can be used as particulate delivery systems, similar in size to certain pathogens while also enabling clustered, oriented and concentrated antigen presentation").
Conclusion
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/OPHELIA A HAWTHORNE/Primary Examiner, Art Unit 3786