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 .
Applicant’s remarks, filed 7/20/2026, are acknowledged and entered into the record. Applicants amended claims 1, 4, 7, 9-10, 15, 18 25 and 27; canceled claims 2, 5-6, 8, 11-14, 16, 19-24 and 26; and added new claims 28-34, in the remarks of 7/20/2026.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The present application is drawn from PCT/US2022/012801, filed 1/18/2022; and claims benefit under 35 U.S.C. 119(e) to U.S. Provisional application 63/138163, filed 1/15/2021.
Status of Claims
Claims 1, 3-4, 7, 9-10, 15, 17-18, 25, 27 and 28-34 are pending and are being examined on the merits.
Claim Rejections – Withdrawn
Claim Rejections - 35 USC § 112(b)
The rejection of claims 7, 9-11, 15, 18-19, 21-22 and 26-27 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn.
Regarding claims 7, 9 and 15; applicants removed the indefinite language, thus obviating the indefiniteness issues.
Regarding claims 11, 19, 21-22 and 26; applicants canceled the claims rendering the rejection moot.
Regarding claim 10, applicants amended the claims to remove the reference to “encapsulating” the adjuvant, thus obviating the indefiniteness.
Regarding claim 18, applicants amended the claim to remove reference to “suitable” intervals, thus obviating the indefiniteness issues.
Regarding claim 27, applicants added the proper conjugate to the list of alternatives, thus obviating the indefiniteness issue.
Claim Rejections - 35 USC § 112(d)
The rejection of claim 13 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the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends, is withdrawn. Claim 13 has been canceled.
Claim Rejections - 35 USC § 112(a)
The rejection of claim 11 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, is withdrawn. Claim 11 has been canceled.
The rejection of claim 10 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, is withdrawn. Claim 10 has been canceled.
Claim Rejections - 35 USC § 102
The rejection of claims 1-7, 11, 15 and 17-18 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Rothman et al., (from IDS of 7/5/2023; US 9,463,227; issued 10/11/2016), is withdrawn. Applicants amended independent claim 1 to include new limitations, whereby the teachings of Rothman does not anticipate all the claim limitations.
The rejection of claims 1-7, 9-10, 15 and 17-18 under 35 U.S.C. 102(a)(1) as being anticipated by Forsbach et al., (EP 1957647; published 4/3/2015). Applicants amended independent claim 1 to include new limitations, whereby the teachings of Forsbach does not anticipate all the claim limitations.
Claim Rejections - New
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.
The factual inquiries 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 1, 3-4, 7, 9, 15, 17-18, 25, 27 and 28-34 are rejected under 35 U.S.C. 103 as being unpatentable over Rothman et al., (from IDS of 7/5/2023; US 9,463,227; issued 10/11/2016) and De Mot et al., (Science Translational Medicine, 2020) and Klemm et al., (Nature Reviews Genetics, 2019).
Rothman et al. teaches methods of providing an adjuvant for enhancing immune responses in a subject (abstract). Rothman teaches listeria monocytogenes and a protein named listeriolysin O (LLO) have strong adjuvant properties (col. 1, lines 33-35). Rothman teaches that administering Listeria vaccine strain can reconstitute the immune response or facilitate the recovery of an immune response in subjects that have undergone cytotoxic treatment as a result of cancer (col. 1, lines 47-50); can improve the immunogenicity of a vaccine when co-administered (col. 2, lines 11-12); or can enhance an immune response against a disease in an antigen-independent manner (col. 2, lines 18-20). Rothman teaches the Listeria vaccine strain is devoid of exogenous antigen (col. 5, lines 4-5). Rothman teaches the invention is for preventing disease, treating disease or vaccinating a human subject, or to enhance the immune response of a human (col. 6, lines 28-32). Rothman teaches the immune response elicited comprises an innate immune response wherein M1 macrophages and dendritic cells (DC) are activated (col. 25, lines 18-21). Rothman teaches “a poorly described property of LLO is its ability to induce epigenetic modifications affecting control of DNA expression; extracellular LLO induces a dephosphorylation of the histone protein H3 and a similar deacetylation of the histone H4.” This epigenetic effect provides a mechanism by which LLO may regulate the expression of gene products required for immune responses (col. 26, lines 44-60). Rothman teaches the present invention provides a method of eliciting an enhanced immune response to an infectious disease in a subject; in an embodiment, the immune response is not antigen specific (col. 30, lines 19-25).
However, Rothman does not teach monitoring the individual for epigenetic changes in myeloid cells.
De Mot et al. teaches the transcriptional profiles of adjuvanted hepatitis B vaccines share a core signature (title). De Mot teaches that adjuvants in human vaccines can potentiate the immunogenicity of vaccine antigens through activation of a complex network of innate immune responses (pg. 1, col. 1, para. 1). De Mot evaluates the gene expression profiles in cells in whole blood elicited in naïve subjects receiving two doses of vaccines containing the prototypic hepatitis B virus surface antigen (i.e. HBsAg; which is non-pathogenic), formulated with AS01B, AS01E, AS03 or AS04 (pg. 1, col. 1, para. 2). De Mot teaches the adjuvants AS01B and AS01E comprise MPL (which is a TLR4 ligand) and saponin; while AS03 contains α-tocopherol in an oil-in-water emulsion, which is squalene-based (see instant specs., pg. 59, para. 00194). De Mot teaches the baseline-correlated gene expression changes in cells from whole blood which are induced by adjuvanted vaccines (pg. 2, Fig. 1). De Mot teaches the analyzed cells from whole blood include myeloid cells, dendritic cells and NK cells (pg. 8, col. 2, para. 2). De Mot analyses the changes in gene expression using fragmented cDNA hybridized using a GeneChip (pg. 10, col. 2, para. 4).
Thus, De Mot teaches that adjuvants stimulate a core innate gene signature characterized by altered expression of genes in innate immune cells such as myeloid cells, dendritic cells and NK cells.
It would have been obvious to one of skill in the art to modify the method of administering an adjuvant which stimulates innate immunity in myeloid cells, of Rothman, to further comprise a step of monitoring the gene expression changes in the myeloid cells. One would have been motivated to do so in order to characterize the changes in gene expression which promote the enhanced innate immunity, as described by De Mot. There would have been a reasonable expectation for success given that De Mot uses a GeneChip microarray to characterize the changes in gene expression resulting from administration of vaccines with various different adjuvants as a comparison study of the core changes in gene regulation that are shared across different vaccine adjuvants.
However, neither Rothman nor De Mot teach measuring chromatin accessibility (i.e. epigenetic changes) associated with the altered gene expression related to enhanced innate immunity in response to different vaccine adjuvants.
Klemm teaches chromatin accessibility and the regulatory genome (title). Klemm teaches physical access to DNA is a highly dynamic property of chromatin that plays an essential role in establishing and maintaining cellular identity; and that the organization of accessible chromatin across the genome reflects a network of permissible physical interactions through which enhancers, promoters, insulators and chromatin-binding factors cooperatively regulate gene expression. Klemm teaches the chromatin accessibility and regulatory elements withing the genome are epigenetic features which are dynamically established to control gene expression (abstract). Klemm teaches methods of measuring chromatin accessibility (pg. 208, col. 1, para. 2), including using DNase-seq or ATAC-seq. Klemm teaches ATAC-seq has been widely adopted in part because it robustly identifies accessible chromatin, is straightforward and rapidly implemented and is amendable to materially limited clinical and primary tissue samples (pg. 208, col. 2, para. 2). Thus, Klemm teaches the art of utilizing ATAC-seq to measure epigenetic changes in chromatin accessibility as underlying mechanisms which regulate changes in gene expression.
It would have been obvious to one of skill in the art to modify the methods of administering an adjuvant which stimulates innate immunity in myeloid cells and further comprises monitoring the resulting changes in gene expression, to further comprise a step of monitoring epigenetic changes in the myeloid cells. One would have been motivated to do so in order to characterize the changes in gene expression which promote the enhanced innate immunity, as taught by De Mot. There would have been a reasonable expectation for success given that epigenetic changes in chromatin accessibility are one mechanism that underlies changes in gene expression, and that changes in chromatin accessibility are measured by ATAC-seq assays, as taught by Klemm et al. Thus, the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Regarding claims 1 and 15; the combination method of Rothman, De Mot, and Klemm comprises administering Listeria-based LLO, which acts as an adjuvant which epigenetically enhances the innate immune response, and which is not antigen-specific, and further comprises monitoring the gene expression changes resulting from the adjuvant, as taught by De Mot, and includes ATAC-seq analysis of underlying changes in chromatin accessibility as correlates of the altered gene expression, as taught by Klemm. Further, Rothman teaches the immune response of the methods of the invention are a prophylactic immune response (col. 8, line 40) and may be used to treat, or protect people at risk of, any infectious disease, including viral infections and influenza (col. 8, lines 47-49; see also col. 31, lines 46-49). Thus, the combination methods of Rothman, De Mot and Klemm make obvious the methods of instant claims 1 and 15.
Regarding claim 3, Rothman teaches a live attenuated Listeria vaccine strain devoid of antigen that enables the Listeria to secrete only the non-hemolytic form of LLO as an adjuvant; the invention provided herein addresses the first live adjuvant (col. 5, lines 7-12). Rothman teaches a method of enhancing an immune response against a disease in an antigen-independent manner (col. 9, lines 15-16); and that the Listeria-based adjuvant is used alone or is combined with another adjuvant (col. 9, lines 44-45). Thus, Rothman teaches Listeria-based adjuvant compositions that lack additional antigens, or wherein the composition consists of only an adjuvant (re. claim 3). Thus, the methods of Rothman anticipate instant claim 3.
Regarding claims 4, 7, 9 and 34; Rothman teaches that, in one embodiment, the invention relates to a method of improving the immunogenicity of a vaccine, said method comprising the step of co-administering the vaccine and a Listeria-based LLO adjuvant to a subject (col. 2, lines 11-14). Rothman teaches the Lysteria-based adjuvant may be used alone or is combined with an additional adjuvant, which may be monophosphoryl lipid A (i.e. MPL; a known TLR4 agonist; col. 9, lines 44-45 and 57-58). Thus, Rothman teaches wherein the immunostimulatory composition may consist of an adjuvant and a non-pathogen antigen; in this case the LLO is the non-pathogen antigen and MPL is the adjuvant. Alternatively, De Mot teaches administering the prototypic hepatitis B virus surface antigen (i.e., HBsAg) formulated in AS01B (pg. 1, col. 1, para. 2). HBsAg is a non-pathogenic antigen and the AS01B adjuvant comprises MPL. Thus, each of Rothman and De Mot teach compositions consisting of an adjuvant and a non-pathogen antigen. Thus, the combination methods of Rothman, De Mot and Klemm make obvious instant claim 4. Further, as Rothman teaches the LLO may be administered with an alternative adjuvant, which may be any adjuvant known in the art (col. 10, lines 8-9), or wherein the adjuvant is MPL, and De Mot teaches AS01B is an art-recognized adjuvant comprising MPL, the combination of Rothman, De Mot and Klemm make obvious wherein the adjuvant is AS01B, and make obvious instant claims 7 and 34. As MPL, of the AS01B adjuvant, is a known TLR4 agonist, the combination of Rothman, De Mot and Klemm make obvious instant claim 9.
Regarding claim 17; Rothman teaches the method is provided to reconstitute the immune response or facilitate the recovery of an immune response to normal levels in subjects that have undergone cytotoxic treatment as a result of cancer (col. 1, lines 47-50). Rothman teaches the adjuvant enhances an immune response in an antigen-unspecified manner in order to enable a heightened state of an immune response as it applies to neonates, or older children and adults following cytotoxic treatment (col. 33, lines 1-5). Thus, Rothman teaches the methods are applied to subjects with reduced adaptive immune responses, and therefore the combination of Rothman, De Mot and Klemm make obvious instant claim 17.
Regarding claim 18, Rothman teaches experiments in which the vaccine was administered in mice which were implanted with tumors. Rothman teaches 7 days after tumor implantation the mice were vaccinated; the mice were then administered a booster vaccine one week after the vaccine was given (col. 47, lines 27-32). Thus, Rothman teaches that administration may be repeated at suitable intervals, and therefore the combination of Rothman, De Mot and Klemm make obvious instant claim 18.
Regarding claims 25 and 27; the combination methods of Rothman, De Mot and Klemm are described above, wherein the methods comprise administering an immunostimulatory composition comprising an adjuvant to stimulate innate immunity and further performing ATAC-seq to determine the epigenetic state of the innate cells. Thus the combination methods of Rothman, De Mot and Klemm make obvious the methods of instant claims 25 and 27. It is noted that claim 25 recites “where an epigenetic signature in the innate immune cells of enhanced chromatin accessibility of the IRF1, IRF2, STAT1, STAT2, IRF7, IRF8, STAT5b and USF1 loci is a biomarker to predict susceptibility or resistance to viral infection.” This is not considered an active step to the method, rather it is interpreted as inherent properties of the immune cells, which may, or may not, inform alternative methods, which are distinct from methods for “modulating the epigenome of innate immune cells.” Further, interpreting data and predicting susceptibility or resistance, are abstract ideas relying on mental processes, and not patentable method steps. See MPEP 2106.04(a) and 2106.04(a)(2)(III). Similarly, claim 27 recites “where an epigenetic signature in the innate immune cells of reduced chromatin accessibility of the AP-1, Jun and Fos loci is a biomarker to predict susceptibility to enhanced inflammation or sepsis in viral or bacterial infections.” This is interpreted as an inherent property of the immune cells and informs alternative methods which are distinct from methods for “modulating the epigenome of innate immune cells.”
Regarding claims 28-33; the combination of Rothman and De Mot make obvious wherein the composition consists of an adjuvant (which may be LLO, of Rothman) or wherein the composition comprises adjuvant and non-pathogen antigen (which may be HBsAg and AS01B, of De Mot), as described above. Further, De Mot teaches the adjuvant AS03, which is a water-in-oil emulsion vaccine which comprises squalene. Thus, as the combination of Rothman, De Mot and Klemm make obvious instant claims 25 and 27, which are independent claims, the combination of Rothman, De Mot and Klemm also make obvious instant claims 28-30, which depend from claim 25, as well as instant claims 31-33, which depend from claim 27.
Claims 1, 3-4, 7, 9-10, 15, 17-18, 25, 27 and 28-34 are rejected under 35 U.S.C. 103 as being unpatentable over Forsbach et al., (EP 1957647; published 4/3/2015) and De Mot et al., (Science Translational Medicine, 2020) and Klemm et al., (Nature Reviews Genetics, 2019).
Forsbach et al. teach oligoribonucleotides with immunostimulatory activity (title). Forsbach teaches Toll-like receptors (TLRs) play a critical role in innate immunity, as pattern recognition receptor polypeptides that recognize pathogen-associated molecular patterns (pg. 2, para. 0002). Specifically, Forsbach teaches the immunostimulatory oligoribonucleotides (ORN) of the invention are agonists for TLR8 (pg. 2, para. 0007 – pg. 3, top). Forsbach teaches the ORN of the invention is used to activate an immune cell, including dendritic cells, NK cells, monocytes and macrophages (pg. 20, para. 0127). Forsbach teaches that a subject can be prepared for a future encounter with an unknown antigen by administering to the subject a composition of an ORN of the invention, wherein the composition does not include an antigen; and whereby the immune system of the subject is prepared to mount a more vigorous response to an antigen that is later encountered by the subject (pg. 21, para. 0140). Thus, Forsbach teaches the ORN of the invention, as well as compositions comprising the ORN and methods of using the ORN, are useful for stimulating or augmenting an immune response (pg. 2, para. 0005); including the step of administering to a subject an effective amount of a composition of an ORN of the invention (pg. 5, para. 0033).
However, Forsbach does not teach monitoring the individual for epigenetic changes in myeloid cells.
De Mot et al. teaches the transcriptional profiles of adjuvanted hepatitis B vaccines share a core signature (title). De Mot teaches that adjuvants in human vaccines can potentiate the immunogenicity of vaccine antigens through activation of a complex network of innate immune responses (pg. 1, col. 1, para. 1). De Mot evaluates the gene expression profiles in cells in whole blood elicited in naïve subjects receiving two doses of vaccines containing the prototypic hepatitis B virus surface antigen (i.e. HBsAg; which is non-pathogenic), formulated with AS01B, AS01E, AS03 or AS04 (pg. 1, col. 1, para. 2). De Mot teaches the adjuvants AS01B and AS01E comprise MPL (which is a TLR4 ligand) and saponin; while AS03 contains α-tocopherol in an oil-in-water emulsion, which is squalene-based (see instant specs., pg. 59, para. 00194). De Mot teaches the baseline-correlated gene expression changes in cells from whole blood which are induced by adjuvanted vaccines (pg. 2, Fig. 1). De Mot teaches the analyzed cells from whole blood include myeloid cells, dendritic cells and NK cells (pg. 8, col. 2, para. 2). De Mot analyses the changes in gene expression using fragmented cDNA hybridized using a GeneChip (pg. 10, col. 2, para. 4).
Thus, De Mot teaches that adjuvants stimulate a core innate gene signature characterized by altered expression of genes in innate immune cells such as myeloid cells, dendritic cells and NK cells.
It would have been obvious to one of skill in the art to modify the method of administering an adjuvant which stimulates innate immunity in myeloid cells, of Forsbach, to further comprise a step of monitoring the gene expression changes in the myeloid cells. One would have been motivated to do so in order to characterize the changes in gene expression which promote the enhanced innate immunity, as described by De Mot. There would have been a reasonable expectation for success given that De Mot uses a GeneChip microarray to characterize the changes in gene expression resulting from administration of vaccines with various different adjuvants as a comparison study of the core changes in gene regulation that are shared across different vaccine adjuvants.
However, neither Forsbach nor De Mot teach measuring chromatin accessibility (i.e. epigenetic changes) associated with the altered gene expression related to enhanced innate immunity in response to different vaccine adjuvants.
Klemm teaches chromatin accessibility and the regulatory genome (title). Klemm teaches physical access to DNA is a highly dynamic property of chromatin that plays an essential role in establishing and maintaining cellular identity; and that the organization of accessible chromatin across the genome reflects a network of permissible physical interactions through which enhancers, promoters, insulators and chromatin-binding factors cooperatively regulate gene expression. Klemm teaches the chromatin accessibility and regulatory elements withing the genome are epigenetic features which are dynamically established to control gene expression (abstract). Klemm teaches methods of measuring chromatin accessibility (pg. 208, col. 1, para. 2), including using DNase-seq or ATAC-seq. Klemm teaches ATAC-seq has been widely adopted in part because it robustly identifies accessible chromatin, is straightforward and rapidly implemented and is amendable to materially limited clinical and primary tissue samples (pg. 208, col. 2, para. 2). Thus, Klemm teaches the art of utilizing ATAC-seq to measure epigenetic changes in chromatin accessibility as underlying mechanisms which regulate changes in gene expression.
It would have been obvious to one of skill in the art to modify the methods of administering an adjuvant which stimulates innate immunity in myeloid cells and further comprises monitoring the resulting changes in gene expression, to further comprise a step of monitoring epigenetic changes in the myeloid cells. One would have been motivated to do so in order to characterize the changes in gene expression which promote the enhanced innate immunity, as taught by De Mot. There would have been a reasonable expectation for success given that epigenetic changes in chromatin accessibility are one mechanism that underlies changes in gene expression, and that changes in chromatin accessibility are measured by ATAC-seq assays, as taught by Klemm et al. Thus, the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Regarding claims 1 and 3; the combination method of Forsbach, De Mot, and Klemm comprises administering an TLR8 ORN, which acts as an adjuvant which activates the innate immune response, and which is not antigen-specific, and further comprises monitoring the gene expression changes resulting from the adjuvant, as taught by De Mot, and includes ATAC-seq analysis of underlying changes in chromatin accessibility as correlates of the altered gene expression, as taught by Klemm. Forsbach teaches an immunostimulatory composition including the immunostimulatory TLR8 ORN of the invention and an adjuvant (pg. 4, para. 0021). Forsbach teaches the ORN composition may be administered with or without an antigen (pg. 5, para. 0033). Forsbach teaches and immune-stimulating adjuvant is an adjuvant that causes activation of a cell of the immune system. Thus, in one aspect the invention provides an adjuvant that includes an immunostimulatory ORN of the invention, by itself. Or, in an alternative embodiment, the invention provides the ORN of the invention and at least one other adjuvant, a combination adjuvant (pg. 15, para. 0097). Thus the invention of Forsbach, comprises administering an immunostimulatory composition comprising the ORN as an adjuvant, to stimulate innate immunity against pathogens, without any additional antigens. The combination of Forsbach, De Mot and Klemm make obvious instant claims 1 and 3.
Regarding claims 4; Forsbach teaches the ORN of the invention may be used as a vaccine, wherein the vaccine consists of the ORN and an antigen (pg. 17, paras. 0106-0107); and whereby the antigen may be an allergen, such as pollen (paras. 0123-0124). Thus the combination of Forsbach, De Mot and Klemm make obvious instant claim 4.
Regarding claims 7; Forsbach teaches the immunostimulatory ORN of the invention are useful alone or in combination with other agents, as adjuvants (pg. 15, para. 0093). Suitable adjuvants include alum; or water-in-oil emulsions, including those comprising squalene, including MF59 (pg. 15, para. 0094). Thus, the methods and compositions of the combination of Forsbach, De Mot and Klemm make obvious instant claim 7.
Regarding claim 9; Forsbach teaches the adjuvant ORN of the invention is a TLR8 agonist (pg. 2, para. 0007); thus the combination of Forsbach, De Mot and Klemm make obvious instant claim 9.
Regarding claim 10, Forsbach teaches a pharmaceutical composition which includes a composition of the ORN of the invention in association with a delivery vehicle. In various embodiment the delivery vehicle can be chosen from a liposome, a microparticle or a nanosphere (pg. 19, para. 0126). Thus, the combination of Forsbach, De Mot and Klemm make obvious instant claim 10.
Regarding claim 15; Forsbach teaches the use in therapy of the invention may be for the purpose of immunization, i.e. prophylactic (pg. 30, para. 0226); that the word “treat” shall mean to prevent or ameliorate (pg. 21, para. 0146); including a subject having an infection, which may be a viral infection (pg. 21, para. 0147). Forsbach teaches a method of vaccinating a subject may include the composition of an ORN and an antigen (pg. 21, para. 0139); and that the invention contemplates that a subject can be prepared for a future encounter with an unknown antigen by administering to the subject a composition of an ORN of the invention (pg. 21, para. 0140). Thus, the invention of Forsbach encompasses use of the ORN in compositions as prophylactic to a viral infection, or as a vaccine, and thus the combination of Forsbach, De Mot and Klemm make obvious instant claim 15.
Regarding claim 17-18; Forsbach teaches treating a subject having an immune system deficiency, such as suppressed CD4+ T-cell population; and thus the combination of Forsbach, De Mot and Klemm make obvious instant claim 17. Forsbach teaches the method also contemplates the administration of one or more booster doses of the composition following an initial administration (pg. 21, para. 0139). Thus, the combination of Forsbach, De Mot and Klemm make obvious instant claim 18.
Regarding claims 25 and 27; the combination methods of Forsbach, De Mot and Klemm are described above, wherein the methods comprise administering an immunostimulatory composition comprising an adjuvant (i.e. the TLR8 ORN of Forsbach) to stimulate innate immunity and further performing ATAC-seq to determine the epigenetic state of the innate cells as described by the combination of De Mot and Klemm. Thus the combination methods of Forsbach, De Mot and Klemm make obvious the methods of instant claims 25 and 27. The resulting “epigenetic signature” is considered an inherent property of the methods, and is described as a basis for an alternative method of predicting (i.e. diagnosing); and thus is not considered an active step limitation of the methods of claims 25 or 27.
Regarding claims 28-33; the Forsbach makes obvious wherein the composition consists of an adjuvant (which may be the TLR8 ORN, of Forsbach) or wherein the composition comprises adjuvant and non-pathogen antigen (which may be theTLR8 ORN and pollen), as described above. Further, Forsbach teaches the adjuvant MF59, which is a squalene-in-water emulsion vaccine (para. 0094). Thus, as the combination of Forsbach, De Mot and Klemm make obvious instant claims 25 and 27, which are independent claims, the combination of Forsbach, De Mot and Klemm also make obvious instant claims 28-30, which depend from claim 25, as well as instant claims 31-33, which depend from claim 27.
Regarding claim 34, the combination of Forsbach, De Mot and Flemm make obvious a method for modulating the epigenome comprising administering an immunostimulatory composition consisting of TLR8 ORN and MF59, as described above; whereby it is inherent that the composition which activates immune cells causes changes in gene expression and inherently encompasses the underlying epigenetic modifications in the chromatin accessibility which underlie the changes in gene expression. Thus the combination of Forsbach, De Mot and Flemm make obvious instant claim 34.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES R. MELCHIOR whose telephone number is (703)756-4761. The examiner can normally be reached M-F 8:00-5:00 CST.
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, Samira Jean-Louis can be reached at (571) 270-3503. 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.
/JAMES RYLAND MELCHIOR/Examiner, Art Unit 1644
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
Prosecution Insights