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 1-7, 9-25, 35, 37, 42, 72, 73, 75, 76, 78, and 84-87 are pending and currently under consideration.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 3-5, 9, 13, 15, 16, 18, 20-23, 25, 35, 37, 42, 72, 75, 76, 78, 85, and 87 are rejected under 35 U.S.C. 103(a) as being unpatentable over Valiante et al (WO 2017/070618 A1; 4/27/17; 12/9/24 IDS) in view of Besin et al (US 2019/0117798 A1; 4/25/19).
Valiante et al teaches RNA vaccines are sued to induce both cellular and humoral immunity and have superior properties to traditional cancer vaccines in that they produce much larger antibody titers and produce responses earlier (lines 1-8 on page 2, in particular). Valiante et al teaches the RNA vaccines include an immune response specific to antigenic polypeptide or immunogenic fragment thereof, wherein titer of anti-antigenic polypeptide antibody that binds specifically to antigenic polypeptide in a subject administered the RNA vaccines increases along with increases in measurable immunogenicity following vaccination (lines 6-14 on page 8 and Example 5, in particular). Valiante et al further teaches personalized cancer vaccines comprising mRNA having an open reading frame encoding at least 2 patient specific cancer antigens and a lipid nanoparticle carrier (paragraph spanning pages 2-3, in particular). Valiante et al further teaches said vaccines wherein the mRNA may encode 5-10 cancer antigens (lines 9-10 on page 3, in particular). Valiante et al teaches personalized cancer vaccines wherein the lipid nanoparticle comprises an immune potentiator, such as a TLR agonist (lines 4-5 on page 5, in particular) – which is known to activate an adaptive immune response (lines 25-26 on page 140, in particular). Valiante et al further teaches the mRNA of the vaccine can have chemical modifications (lines 8-11 on page 44, in particular). Valiante et al further teaches basic components of mRNA molecules include at least one coding region, a 5’ UTR, a 3’ UTR, a 5’ cap, and a poly-A tail (first paragraph on page 36, in particular). Valiante et al further teaches RNA vaccines are to treat subjects that are human (lines 12-13 on page 72, in particular). Valiante et al further teaches such RNA vaccines induce humoral immune responses and/or cellular immune responses (lines 1-5 on page 22, in particular) - such as CD8 T-cell immune responses (Figs 1-2, in particular). Valiante et al further teaches RNA cancer vaccines can be administered prophylactically or therapeutically as an active immunization scheme to healthy individuals or early cancer or during active cancer after onset of symptoms (first paragraph on page 74, in particular). Valiante et al further teaches a method of treating cancer in a subject comprising identifying at least two cancer antigens in a sample from the subject, producing such a personalized cancer vaccine encoding the cancer antigens and administering the personalized cancer vaccine to the subject (last paragraph on page 7, in particular). Valiante et al further teaches a method of treating cancer in a subject comprising identifying at least two cancer antigens in a sample from the subject, producing such a personalized cancer vaccine encoding the cancer antigens and administering the personalized cancer vaccine to the subject in combination with a cancer therapeutic agent, such as an anti-PD-1 antibody (such as nivolumab), to the subject (lines 18-27 on page 6, in particular). Valiante et al further teaches such a cancer includes melanoma (line 11 on page 76, in particular). Valiante et al further teaches administering cancer vaccines to subjects with resected tumors in combination with an anti-PD-1 antibody (Examples 9-10, in particular).
Valiante et al does not specifically teach cancer antigens encoded by the personalized mRNA vaccine include NY-ESO-1, MAGE-A3, tyrosinase, and/or TPTE. However, these deficiencies are made up in the teachings of Besin et al.
Besin et al teaches NY-ESO-1, MAGE-A3, and tyrosinase as cancer antigens to be targeted by cancer vaccines ([0114] and [0864], in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising performing a method of Valiante et al of treating a human subject comprising identifying any combination of cancer antigens (such as NY-ESO-1, MAGE-A3, and/or tyrosinase of Besin et al in either the full-length wild-type or mutated form found in the subject) in a sample from subject with any cancer of Valiante et al, producing such a personalized cancer vaccine with mRNA of Valiante et al encoding the cancer antigens (“polyeptopic”) and administering the personalized cancer vaccine to the subject before (where there is evidence of disease at time for administration) or after tumor resection (where there is no evidence of disease at time for administration) optionally in combination with a cancer therapeutic agent, such as an anti-PD-1 antibody immunotherapeutic (such as nivolumab of Valiante et al), and measuring an immune response of Valiante et al in the subject as an indication the subject is therapeutically responding to the treatment because Valiante et al teaches subjects prophylactically and therapeutically respond to such treatments and Besin et al teaches NY-ESO-1, MAGE-A3, and/or tyrosinase as cancer antigens. This is an example of (i) some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention and/or (ii) a simple substitution of one known element (mRNA encoding cancer antigen(s)) for another (mRNA encoding cancer antigen(s) of Besin et al) to obtain predictable results. See MPEP 2143.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA has chemical modifications of Valiante et al (lines 8-11 on page 44, in particular) and perform said combined method wherein the mRNA does not have chemical modifications of Valiante et al (“natural ribonucleotides”) to determine whether such chemical modifications enhance therapeutic immunogenicity.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 3-5, 7, 9, 12-16, 18, 20-25, 35, 37, 42, 72, 75, 76, 78, 54, 84, 85, and 87 is/are rejected under 35 U.S.C. 103 as being unpatentable over Valiante et al (WO 2017/070618 A1; 4/27/17) in view of Besin et al (US 2019/0117798 A1; 4/25/19) as applied to claims 1, 3-5, 9, 13, 15, 16, 18, 20-23, 25, 35, 37, 42, 72, 75, 76, 78, 85, and 87 above, and further in view of Kranz et al (Nature, 2016, (534): 396-401; 12/9/24 IDS).
Teachings of Valiante et al and Bensin et al are discussed above.
Valiante et al and Bensin et al do not specifically teach the cancer antigen TPTE, that the mRNA of the vaccine encodes a signal peptide, that the vaccine expresses the cancer antigens in dendritic cells in lymphoid tissue of the subject, or that the vaccine induces an “adaptive” immune response. However, these deficiencies are made up in the teachings of Kranz et al.
Kranz et al teaches targeting dendritic cells (DCs) with mRNA-lipid particle vaccines because DCs are antigen presenting cells in lymphoid organs that are in close proximity to T cells and that such targeting results in an adaptive and innate immune response (Abstract, in particular). Kranz et al further teaches cancer antigens encoded by such RNA vaccines include TPTE, as well as NY-ESO-1, MAGE-A3, and/or tyrosinase of Bensin et al (right column on page 399, Extended Data Figures 2 and 5, in particular). Kranz et al further teaches adding a signal sequence to the mRNA of the vaccine in order to route to the ER and MHC class I transmembrane and cytoplasmic domains for improved presentation of MHC class I and II epitopes (left column on page 402, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method using lipid particles of Kranz et al or Valiante et al wherein the mRNA vaccine further comprise mRNA encoding TPTE, signal sequence, and MHC class I transmembrane and cytoplasmic domains of Kranz et al and results in an adaptive immune response because Kranz et al teaches TPTE, as well as NY-ESO-1, MAGE-A3, and/or tyrosinase of Bensin et al, as a cancer antigen for an mRNA vaccine, Kranz et al further teaches adding a signal sequence to the mRNA of the vaccine in order to route to the ER and MHC class I transmembrane and cytoplasmic domains for improved presentation of MHC class I and II epitopes, and Kranz et al teaches targeting dendritic cells (DCs) with mRNA-lipid particle vaccines results in an adaptive and innate immune response. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA vaccines target and express the mRNA in dendritic cells (DCs), as taught by Kranz et al, because DCs are antigen presenting cells in lymphoid organs that are in close proximity to T cells that are involved in the immune response of the mRNA vaccines of the combined method. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 3-5, 9, 13, 15, 16, 18, 20-23, 25, 35, 37, 42, 72, 73, 75, 76, 78, 85, and 87 is/are rejected under 35 U.S.C. 103 as being unpatentable over Valiante et al (WO 2017/070618 A1; 4/27/17) in view of Besin et al (US 2019/0117798 A1; 4/25/19) as applied to claims 1, 3-5, 9, 13, 15, 16, 18, 20-23, 25, 35, 37, 42, 72, 75, 76, 78, 85, and 87 above, and further in view of Burova et al (Mol Cancer Ther, 2017, 16(5): 861-870).
Teachings of Valiante et al and Bensin et al are discussed above.
Valiante et al and Bensin et al do not specifically teach the anti-PD-1 antibody as cemiplima. However, these deficiencies are made up in the teachings of Burova et al.
Burova et al teaches the anti-PD-1 antibody cemiplima (same as “REGN2810”) as a cancer immunotherapeutic (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating a subject with cancer comprising administering an anti-PD-1 antibody immunotherapeutic wherein the anti-PD-1 antibody immunotherapeutic is cemiplima (same as “REGN2810”) of Burova because Burova et al teaches the anti-PD-1 antibody cemiplima (same as “REGN2810”) as a cancer immunotherapeutic (Abstract, in particular). This is an example of a simple substation of one known element for another to obtain predictable results. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1-6, 9, 13, 15, 16, 18, 20-23, 25, 35, 37, 42, 72, 75, 76, 78, 85, and 87 is/are rejected under 35 U.S.C. 103 as being unpatentable over Valiante et al (WO 2017/070618 A1; 4/27/17) in view of Besin et al (US 2019/0117798 A1; 4/25/19) as applied to claims 1, 3-5, 9, 13, 15, 16, 18, 20-23, 25, 35, 37, 42, 72, 75, 76, 78, 85, and 87 above, and further in view of Eisenhauer et al (European Journal of Cancer, 2009, 45: 228-247; 12/9/24 IDS).
Teachings of Valiante et al and Bensin et al are discussed above.
Valiante et al and Bensin et al do not specifically teach RECIST. However, these deficiencies are made up in the teachings of Eisenhauer et al.
Eisenhauer et al teaches RECIST 1.1 to classify tumor burden in subjects (Abstract, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of prophylactically or therapeutically treating a subject with cancer wherein the subject is classified according to RECIST 1.1 before and after treatment in order to provide the subject with an evaluation of the success of the treatment as compared to baseline because Eisenhauer et al teaches RECIST 1.1 to classify tumor burden in subjects (Abstract, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 3-5, 9, 13, 15-18, 20-23, 25, 35, 37, 42, 72, 75, 76, 78, 85, and 87 is/are rejected under 35 U.S.C. 103 as being unpatentable over Valiante et al (WO 2017/070618 A1; 4/27/17) in view of Besin et al (US 2019/0117798 A1; 4/25/19) as applied to claims 1, 3-5, 9, 13, 15, 16, 18, 20-23, 25, 35, 37, 42, 72, 75, 76, 78, 85, and 87 above, and further in view of Islam et al (Biomater Sci, 2015, 3: 1519-1533).
Teachings of Valiante et al and Bensin et al are discussed above.
Valiante et al and Bensin et al do not describe a poly-A tail as comprising a “modified adenine sequence”. However, these deficiencies are made up in the teachings of Islam et al.
Islam et al teaches additional adenine residues confer stability to in vitro transcribed and capped mRNA and may increase its translational efficiency and, where direct comparisons have been made, longer poly(A) tails ˃adenine have generally been found to preferable to smaller ones (left column on page 1521, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the poly(A) tails are modified to comprise sequences that have been modified to comprise more adenines because Islam et al teaches additional adenine residues confer stability to in vitro transcribed and capped mRNA and may increase its translational efficiency and, where direct comparisons have been made, longer poly(A) tails ˃adenine have generally been found to preferable to smaller ones (left column on page 1521, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 3-5, 9-11, 13, 15, 16, 18, 20-23, 25, 35, 37, 42, 72, 75, 76, 78, and 84-87 is/are rejected under 35 U.S.C. 103 as being unpatentable over Valiante et al (WO 2017/070618 A1; 4/27/17) in view of Besin et al (US 2019/0117798 A1; 4/25/19) as applied to claims 1, 3-5, 9, 13, 15, 16, 18, 20-23, 25, 35, 37, 42, 72, 75, 76, 78, 85, and 87 above, and further in view of Wen et al (Vaccine, 2014, 32(35): 4420-4427) and Williams et al (Cancer Immunol Immunother, 2008, 57: 1635-1645).
Teachings of Valiante et al and Bensin et al are discussed above.
Valiante et al and Bensin et al do not describe personalized mRNA vaccine as encoding a CD4+ epitope, such as a tetanus toxoid CD4+ epitope, and inducing a CD4+ T-cell response. However, these deficiencies are made up in the teachings of Wen et al and Williams et al.
Wen et al teaches tetanus toxoid universal CD4+ T cell epitope P2 expression improves cancer vaccine potential, resulting in higher neutralizing antibody titers (Abstract, in particular).
Williams et al teaches tetanus toxin P2 epitope as a highly immunogenic peptide that enhances tumor antigen specific immune response and provides T cell help to humoral immune responses targeting cell-surface antigens and enhance both CD8+ CTL and CD4+ th response, providing capacity for CD8+ T cell memory (left column on page 1636, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA of the vaccine further encodes a tetanus toxoid CD4+ T cell epitope P2 peptide in an effort to improve the vaccine potential, enhance a CD8+ T cell and CD4+ T cell immune response, and result in adaptive immunity because Wen et al teaches tetanus toxoid universal CD4+ T cell epitope P2 expression improves cancer vaccine potential, resulting in higher neutralizing antibody titers (Abstract, in particular) and Williams et al teaches tetanus toxin P2 epitope as a highly immunogenic peptide that enhances tumor antigen specific immune response and provides T cell help to humoral immune responses targeting cell-surface antigens and enhance both CD8+ CTL and CD4+ th response, providing capacity for CD8+ T cell memory (left column on page 1636, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 3-5, 7, 9-16, 18-25, 35, 37, 42, 72, 75, 76, 78, 54, and 84-87 is/are rejected under 35 U.S.C. 103 as being unpatentable over Valiante et al (WO 2017/070618 A1; 4/27/17) in view of Besin et al (US 2019/0117798 A1; 4/25/19) and Kranz et al (Nature, 2016, (534): 396-401), as applied to claims 1, 3-5, 7, 9, 12-16, 18, 20-25, 35, 37, 42, 72, 75, 76, 78, 54, 84, 85, and 87 above, and further in view of Kreiter et al (The Journal of Immunology, 2008, 180: 309-318; 12/9/24 IDS), Wen et al (Vaccine, 2014, 32(35): 4420-4427), and Williams et al (Cancer Immunol Immunother, 2008, 57: 1635-1645).
Teachings of Valiante et al, Bensin et al, and Kranz et al are discussed above.
Valiante et al, Bensin et al, and Kranz et al do not describe personalized mRNA vaccine as encoding a CD4+ epitope, such as a tetanus toxoid CD4+ epitope, and inducing a CD4+ T-cell response. However, these deficiencies are made up in the teachings of Kreiter et al, Wen et al, and Williams et al.
Kreiter et al teaches increasing antigen presentation in antigen produced by dendritic cells by generating in the dendritic cells antigens with N-terminal leader peptides (signal sequence) and C-terminal MITD MHC class I trafficking signal of Kranz et al (Abstract, in particular).
Wen et al teaches tetanus toxoid universal CD4+ T cell epitope P2 expression improves cancer vaccine potential, resulting in higher neutralizing antibody titers (Abstract, in particular).
Williams et al teaches tetanus toxin P2 epitope as a highly immunogenic peptide that enhances tumor antigen specific immune response and provides T cell help to humoral immune responses targeting cell-surface antigens and enhance both CD8+ CTL and CD4+ th response, providing capacity for CD8+ T cell memory (left column on page 1636, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA of the vaccine further encodes a tetanus toxoid CD4+ T cell epitope P2 peptide in an effort to improve the vaccine potential, enhance a CD8+ T cell and CD4+ T cell immune response, and result in adaptive immunity because Wen et al teaches tetanus toxoid universal CD4+ T cell epitope P2 expression improves cancer vaccine potential, resulting in higher neutralizing antibody titers (Abstract, in particular) and Williams et al teaches tetanus toxin P2 epitope as a highly immunogenic peptide that enhances tumor antigen specific immune response and provides T cell help to humoral immune responses targeting cell-surface antigens and enhance both CD8+ CTL and CD4+ th response, providing capacity for CD8+ T cell memory (left column on page 1636, in particular). This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143.
Further, of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA vaccine comprises, 5’ to 3’:
a 5’ cap of Valiante et al (known basic component of a typical mRNA molecule);
a 5’ UTR of Valiante et al (known basic component of a typical mRNA molecule);
an N-terminal signal peptide of Kreiter et al (increase antigen presentation);
a coding region encoding cancer antigen(s) of the mRNA vaccine of Besin et al;
tetanus toxoid P2 of Wen et al and Williams et al (increase immune response);
a MITD domain of Kranz et al and Kreiter et al (increase antigen presentation);
a 3’ UTR of Valiante et al (known basic component of a typical mRNA molecule); and
a poly-adenine tail of Valiante et al (known basic component of a typical mRNA molecule).
This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claims 1-7, 9-25, 35, 37, 42, 72, 73, 75, 76, 78, and 84-87 are rejected under 35 U.S.C. 103(a) as being unpatentable over Sahin et al (WO 2013/143683 A1; 10/3/13; 12/9/24 IDS) in view of Valiante et al (WO 2017/070618 A1; 4/27/17; 12/9/24 IDS), Besin et al (US 2019/0117798 A1; 4/25/19), Kranz et al (Nature, 2016, (534): 396-401; 12/9/24 IDS), Burova et al (Mol Cancer Ther, 2017, 16(5): 861-870), Eisenhauer et al (European Journal of Cancer, 2009, 45: 228-247; 12/9/24 IDS), Islam et al (Biomater Sci, 2015, 3: 1519-1533), Kreiter et al (The Journal of Immunology, 2008, 180: 309-318; 12/9/24 IDS), Wen et al (Vaccine, 2014, 32(35): 4420-4427), and Williams et al (Cancer Immunol Immunother, 2008, 57: 1635-1645).
Sahin et al teaches methods of treating subjects with cancer comprising administering mRNA vaccines encoding tumor antigen(s) and lipid to the subject.
Sahin et al does not specifically demonstrate administering the mRNA vaccines encoding target antigens, wherein the vaccines comprise additional recited mRNA components, a recited step of administering an anti-PD-1 therapeutic, or other characteristics of recited subjects. However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising performing a method of Sahin et al comprising that of Valiante et al of treating a human subject comprising identifying any combination of cancer antigens (such as NY-ESO-1, MAGE-A3, and/or tyrosinase of Besin et al in either the full-length wild-type or mutated form found in the subject) in a sample from subject with any cancer of Valiante et al, producing such a personalized cancer vaccine with mRNA of Valiante et al encoding the cancer antigens (“polyeptopic”) and administering the personalized cancer vaccine to the subject before (where there is evidence of disease at time for administration) or after tumor resection (where there is no evidence of disease at time for administration) optionally in combination with a cancer therapeutic agent, such as an anti-PD-1 antibody immunotherapeutic (such as nivolumab of Valiante et al), and measuring an immune response of Valiante et al in the subject as an indication the subject is therapeutically responding to the treatment because Valiante et al teaches subjects prophylactically and therapeutically respond to such treatments and Besin et al teaches NY-ESO-1, MAGE-A3, and/or tyrosinase as cancer antigens.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA has chemical modifications of Valiante et al (lines 8-11 on page 44, in particular) and perform said combined method wherein the mRNA does not have chemical modifications of Valiante et al (“natural ribonucleotides”) to determine whether such chemical modifications enhance therapeutic immunogenicity.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method using lipid particles of Kranz et al or Valiante et al wherein the mRNA vaccine further comprise mRNA encoding TPTE, signal sequence, and MHC class I transmembrane and cytoplasmic domains of Kranz et al and results in an adaptive immune response because Kranz et al teaches TPTE, as well as NY-ESO-1, MAGE-A3, and/or tyrosinase of Bensin et al, as a cancer antigen for an mRNA vaccine, Kranz et al further teaches adding a signal sequence to the mRNA of the vaccine in order to route to the ER and MHC class I transmembrane and cytoplasmic domains for improved presentation of MHC class I and II epitopes, and Kranz et al teaches targeting dendritic cells (DCs) with mRNA-lipid particle vaccines results in an adaptive and innate immune response.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA vaccines target and express the mRNA in dendritic cells (DCs), as taught by Kranz et al, because DCs are antigen presenting cells in lymphoid organs that are in close proximity to T cells that are involved in the immune response of the mRNA vaccines of the combined method.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating a subject with cancer comprising administering an anti-PD-1 antibody immunotherapeutic wherein the anti-PD-1 antibody immunotherapeutic is cemiplima (same as “REGN2810”) of Burova because Burova et al teaches the anti-PD-1 antibody cemiplima (same as “REGN2810”) as a cancer immunotherapeutic (Abstract, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of prophylactically or therapeutically treating a subject with cancer wherein the subject is classified according to RECIST 1.1 before and after treatment in order to provide the subject with an evaluation of the success of the treatment as compared to baseline because Eisenhauer et al teaches RECIST 1.1 to classify tumor burden in subjects (Abstract, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the poly(A) tails are modified to comprise sequences that have been modified to comprise more adenines because Islam et al teaches additional adenine residues confer stability to in vitro transcribed and capped mRNA and may increase its translational efficiency and, where direct comparisons have been made, longer poly(A) tails ˃adenine have generally been found to preferable to smaller ones (left column on page 1521, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA of the vaccine further encodes a tetanus toxoid CD4+ T cell epitope P2 peptide in an effort to improve the vaccine potential, enhance a CD8+ T cell and CD4+ T cell immune response, and result in adaptive immunity because Wen et al teaches tetanus toxoid universal CD4+ T cell epitope P2 expression improves cancer vaccine potential, resulting in higher neutralizing antibody titers (Abstract, in particular) and Williams et al teaches tetanus toxin P2 epitope as a highly immunogenic peptide that enhances tumor antigen specific immune response and provides T cell help to humoral immune responses targeting cell-surface antigens and enhance both CD8+ CTL and CD4+ th response, providing capacity for CD8+ T cell memory (left column on page 1636, in particular).
Further, of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA vaccine comprises, 5’ to 3’:
a 5’ cap of Valiante et al (known basic component of a typical mRNA molecule);
a 5’ UTR of Valiante et al (known basic component of a typical mRNA molecule);
an N-terminal signal peptide of Kreiter et al (increase antigen presentation);
a coding region encoding cancer antigen(s) of the mRNA vaccine of Besin et al;
tetanus toxoid P2 of Wen et al and Williams et al (increase immune response);
a MITD domain of Kranz et al and Kreiter et al (increase antigen presentation);
a 3’ UTR of Valiante et al (known basic component of a typical mRNA molecule); and
a poly-adenine tail of Valiante et al (known basic component of a typical mRNA molecule).
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-7, 9-25, 35, 37, 42, 72, 73, 75, 76, 78, and 84-87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of U.S. Patent No. 10485884 in view of Valiante et al (WO 2017/070618 A1; 4/27/17; 12/9/24 IDS), Besin et al (US 2019/0117798 A1; 4/25/19), Kranz et al (Nature, 2016, (534): 396-401; 12/9/24 IDS), Burova et al (Mol Cancer Ther, 2017, 16(5): 861-870), Eisenhauer et al (European Journal of Cancer, 2009, 45: 228-247; 12/9/24 IDS), Islam et al (Biomater Sci, 2015, 3: 1519-1533), Kreiter et al (The Journal of Immunology, 2008, 180: 309-318; 12/9/24 IDS), Wen et al (Vaccine, 2014, 32(35): 4420-4427), and Williams et al (Cancer Immunol Immunother, 2008, 57: 1635-1645).
The instant claims and the patent claims are both drawn to treating subjects with comprising administering mRNA vaccines and lipid wherein the mRNA encodes target antigens. The instant claims differ from the copending claims due to recited target antigens, additional recited mRNA components, a recited step of administering an anti-PD-1 therapeutic, and other characteristics of recited subjects.
However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising performing a method of the patent claims comprising that of Valiante et al of treating a human subject comprising identifying any combination of cancer antigens (such as NY-ESO-1, MAGE-A3, and/or tyrosinase of Besin et al in either the full-length wild-type or mutated form found in the subject) in a sample from subject with any cancer of Valiante et al, producing such a personalized cancer vaccine with mRNA of Valiante et al encoding the cancer antigens (“polyeptopic”) and administering the personalized cancer vaccine to the subject before (where there is evidence of disease at time for administration) or after tumor resection (where there is no evidence of disease at time for administration) optionally in combination with a cancer therapeutic agent, such as an anti-PD-1 antibody immunotherapeutic (such as nivolumab of Valiante et al), and measuring an immune response of Valiante et al in the subject as an indication the subject is therapeutically responding to the treatment because Valiante et al teaches subjects prophylactically and therapeutically respond to such treatments and Besin et al teaches NY-ESO-1, MAGE-A3, and/or tyrosinase as cancer antigens.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA has chemical modifications of Valiante et al (lines 8-11 on page 44, in particular) and perform said combined method wherein the mRNA does not have chemical modifications of Valiante et al (“natural ribonucleotides”) to determine whether such chemical modifications enhance therapeutic immunogenicity.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method using lipid particles of Kranz et al or Valiante et al wherein the mRNA vaccine further comprise mRNA encoding TPTE, signal sequence, and MHC class I transmembrane and cytoplasmic domains of Kranz et al and results in an adaptive immune response because Kranz et al teaches TPTE, as well as NY-ESO-1, MAGE-A3, and/or tyrosinase of Bensin et al, as a cancer antigen for an mRNA vaccine, Kranz et al further teaches adding a signal sequence to the mRNA of the vaccine in order to route to the ER and MHC class I transmembrane and cytoplasmic domains for improved presentation of MHC class I and II epitopes, and Kranz et al teaches targeting dendritic cells (DCs) with mRNA-lipid particle vaccines results in an adaptive and innate immune response.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA vaccines target and express the mRNA in dendritic cells (DCs), as taught by Kranz et al, because DCs are antigen presenting cells in lymphoid organs that are in close proximity to T cells that are involved in the immune response of the mRNA vaccines of the combined method.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating a subject with cancer comprising administering an anti-PD-1 antibody immunotherapeutic wherein the anti-PD-1 antibody immunotherapeutic is cemiplima (same as “REGN2810”) of Burova because Burova et al teaches the anti-PD-1 antibody cemiplima (same as “REGN2810”) as a cancer immunotherapeutic (Abstract, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of prophylactically or therapeutically treating a subject with cancer wherein the subject is classified according to RECIST 1.1 before and after treatment in order to provide the subject with an evaluation of the success of the treatment as compared to baseline because Eisenhauer et al teaches RECIST 1.1 to classify tumor burden in subjects (Abstract, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the poly(A) tails are modified to comprise sequences that have been modified to comprise more adenines because Islam et al teaches additional adenine residues confer stability to in vitro transcribed and capped mRNA and may increase its translational efficiency and, where direct comparisons have been made, longer poly(A) tails ˃adenine have generally been found to preferable to smaller ones (left column on page 1521, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA of the vaccine further encodes a tetanus toxoid CD4+ T cell epitope P2 peptide in an effort to improve the vaccine potential, enhance a CD8+ T cell and CD4+ T cell immune response, and result in adaptive immunity because Wen et al teaches tetanus toxoid universal CD4+ T cell epitope P2 expression improves cancer vaccine potential, resulting in higher neutralizing antibody titers (Abstract, in particular) and Williams et al teaches tetanus toxin P2 epitope as a highly immunogenic peptide that enhances tumor antigen specific immune response and provides T cell help to humoral immune responses targeting cell-surface antigens and enhance both CD8+ CTL and CD4+ th response, providing capacity for CD8+ T cell memory (left column on page 1636, in particular).
Further, of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA vaccine comprises, 5’ to 3’:
a 5’ cap of Valiante et al (known basic component of a typical mRNA molecule);
a 5’ UTR of Valiante et al (known basic component of a typical mRNA molecule);
an N-terminal signal peptide of Kreiter et al (increase antigen presentation);
a coding region encoding cancer antigen(s) of the mRNA vaccine of Besin et al;
tetanus toxoid P2 of Wen et al and Williams et al (increase immune response);
a MITD domain of Kranz et al and Kreiter et al (increase antigen presentation);
a 3’ UTR of Valiante et al (known basic component of a typical mRNA molecule); and
a poly-adenine tail of Valiante et al (known basic component of a typical mRNA molecule).
Claims 1-7, 9-25, 35, 37, 42, 72, 73, 75, 76, 78, and 84-87 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 43-44 of U.S. Patent No. 11559587 in view of Valiante et al (WO 2017/070618 A1; 4/27/17; 12/9/24 IDS), Besin et al (US 2019/0117798 A1; 4/25/19), Kranz et al (Nature, 2016, (534): 396-401; 12/9/24 IDS), Burova et al (Mol Cancer Ther, 2017, 16(5): 861-870), Eisenhauer et al (European Journal of Cancer, 2009, 45: 228-247; 12/9/24 IDS), Islam et al (Biomater Sci, 2015, 3: 1519-1533), Kreiter et al (The Journal of Immunology, 2008, 180: 309-318; 12/9/24 IDS), Wen et al (Vaccine, 2014, 32(35): 4420-4427), and Williams et al (Cancer Immunol Immunother, 2008, 57: 1635-1645).
The instant claims and the patent claims are both drawn to treating subjects with comprising administering mRNA vaccines and lipid wherein the mRNA encodes target antigens. The instant claims differ from the copending claims due to recited target antigens, additional recited mRNA components, a recited step of administering an anti-PD-1 therapeutic, and other characteristics of recited subjects.
However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising performing a method of the patent claims comprising that of Valiante et al of treating a human subject comprising identifying any combination of cancer antigens (such as NY-ESO-1, MAGE-A3, and/or tyrosinase of Besin et al in either the full-length wild-type or mutated form found in the subject) in a sample from subject with any cancer of Valiante et al, producing such a personalized cancer vaccine with mRNA of Valiante et al encoding the cancer antigens (“polyeptopic”) and administering the personalized cancer vaccine to the subject before (where there is evidence of disease at time for administration) or after tumor resection (where there is no evidence of disease at time for administration) optionally in combination with a cancer therapeutic agent, such as an anti-PD-1 antibody immunotherapeutic (such as nivolumab of Valiante et al), and measuring an immune response of Valiante et al in the subject as an indication the subject is therapeutically responding to the treatment because Valiante et al teaches subjects prophylactically and therapeutically respond to such treatments and Besin et al teaches NY-ESO-1, MAGE-A3, and/or tyrosinase as cancer antigens.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA has chemical modifications of Valiante et al (lines 8-11 on page 44, in particular) and perform said combined method wherein the mRNA does not have chemical modifications of Valiante et al (“natural ribonucleotides”) to determine whether such chemical modifications enhance therapeutic immunogenicity.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method using lipid particles of Kranz et al or Valiante et al wherein the mRNA vaccine further comprise mRNA encoding TPTE, signal sequence, and MHC class I transmembrane and cytoplasmic domains of Kranz et al and results in an adaptive immune response because Kranz et al teaches TPTE, as well as NY-ESO-1, MAGE-A3, and/or tyrosinase of Bensin et al, as a cancer antigen for an mRNA vaccine, Kranz et al further teaches adding a signal sequence to the mRNA of the vaccine in order to route to the ER and MHC class I transmembrane and cytoplasmic domains for improved presentation of MHC class I and II epitopes, and Kranz et al teaches targeting dendritic cells (DCs) with mRNA-lipid particle vaccines results in an adaptive and innate immune response.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA vaccines target and express the mRNA in dendritic cells (DCs), as taught by Kranz et al, because DCs are antigen presenting cells in lymphoid organs that are in close proximity to T cells that are involved in the immune response of the mRNA vaccines of the combined method.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating a subject with cancer comprising administering an anti-PD-1 antibody immunotherapeutic wherein the anti-PD-1 antibody immunotherapeutic is cemiplima (same as “REGN2810”) of Burova because Burova et al teaches the anti-PD-1 antibody cemiplima (same as “REGN2810”) as a cancer immunotherapeutic (Abstract, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of prophylactically or therapeutically treating a subject with cancer wherein the subject is classified according to RECIST 1.1 before and after treatment in order to provide the subject with an evaluation of the success of the treatment as compared to baseline because Eisenhauer et al teaches RECIST 1.1 to classify tumor burden in subjects (Abstract, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the poly(A) tails are modified to comprise sequences that have been modified to comprise more adenines because Islam et al teaches additional adenine residues confer stability to in vitro transcribed and capped mRNA and may increase its translational efficiency and, where direct comparisons have been made, longer poly(A) tails ˃adenine have generally been found to preferable to smaller ones (left column on page 1521, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA of the vaccine further encodes a tetanus toxoid CD4+ T cell epitope P2 peptide in an effort to improve the vaccine potential, enhance a CD8+ T cell and CD4+ T cell immune response, and result in adaptive immunity because Wen et al teaches tetanus toxoid universal CD4+ T cell epitope P2 expression improves cancer vaccine potential, resulting in higher neutralizing antibody titers (Abstract, in particular) and Williams et al teaches tetanus toxin P2 epitope as a highly immunogenic peptide that enhances tumor antigen specific immune response and provides T cell help to humoral immune responses targeting cell-surface antigens and enhance both CD8+ CTL and CD4+ th response, providing capacity for CD8+ T cell memory (left column on page 1636, in particular).
Further, of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA vaccine comprises, 5’ to 3’:
a 5’ cap of Valiante et al (known basic component of a typical mRNA molecule);
a 5’ UTR of Valiante et al (known basic component of a typical mRNA molecule);
an N-terminal signal peptide of Kreiter et al (increase antigen presentation);
a coding region encoding cancer antigen(s) of the mRNA vaccine of Besin et al;
tetanus toxoid P2 of Wen et al and Williams et al (increase immune response);
a MITD domain of Kranz et al and Kreiter et al (increase antigen presentation);
a 3’ UTR of Valiante et al (known basic component of a typical mRNA molecule); and
a poly-adenine tail of Valiante et al (known basic component of a typical mRNA molecule).
Claims 1-7, 9-25, 35, 37, 42, 72, 73, 75, 76, 78, and 84-87 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 54, 58-69, and 73-83 of copending Application No. 18/071705 in view of Valiante et al (WO 2017/070618 A1; 4/27/17; 12/9/24 IDS), Besin et al (US 2019/0117798 A1; 4/25/19), Kranz et al (Nature, 2016, (534): 396-401; 12/9/24 IDS), Burova et al (Mol Cancer Ther, 2017, 16(5): 861-870), Eisenhauer et al (European Journal of Cancer, 2009, 45: 228-247; 12/9/24 IDS), Islam et al (Biomater Sci, 2015, 3: 1519-1533), Kreiter et al (The Journal of Immunology, 2008, 180: 309-318; 12/9/24 IDS), Wen et al (Vaccine, 2014, 32(35): 4420-4427), and Williams et al (Cancer Immunol Immunother, 2008, 57: 1635-1645).
The instant claims and the copending claims are both drawn to treating subjects with cancer comprising administering mRNA vaccines and lipid wherein the mRNA encodes the same target antigens. The instant claims differ from the copending claims due to additional recited mRNA components, a recited step of administering an anti-PD-1 therapeutic, and other characteristics of recited subjects.
However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising performing a method of the copending claims comprising that of Valiante et al of treating a human subject comprising identifying any combination of cancer antigens (such as NY-ESO-1, MAGE-A3, and/or tyrosinase of Besin et al in either the full-length wild-type or mutated form found in the subject) in a sample from subject with any cancer of Valiante et al, producing such a personalized cancer vaccine with mRNA of Valiante et al encoding the cancer antigens (“polyeptopic”) and administering the personalized cancer vaccine to the subject before (where there is evidence of disease at time for administration) or after tumor resection (where there is no evidence of disease at time for administration) optionally in combination with a cancer therapeutic agent, such as an anti-PD-1 antibody immunotherapeutic (such as nivolumab of Valiante et al), and measuring an immune response of Valiante et al in the subject as an indication the subject is therapeutically responding to the treatment because Valiante et al teaches subjects prophylactically and therapeutically respond to such treatments and Besin et al teaches NY-ESO-1, MAGE-A3, and/or tyrosinase as cancer antigens.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA has chemical modifications of Valiante et al (lines 8-11 on page 44, in particular) and perform said combined method wherein the mRNA does not have chemical modifications of Valiante et al (“natural ribonucleotides”) to determine whether such chemical modifications enhance therapeutic immunogenicity.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method using lipid particles of Kranz et al or Valiante et al wherein the mRNA vaccine further comprise mRNA encoding TPTE, signal sequence, and MHC class I transmembrane and cytoplasmic domains of Kranz et al and results in an adaptive immune response because Kranz et al teaches TPTE, as well as NY-ESO-1, MAGE-A3, and/or tyrosinase of Bensin et al, as a cancer antigen for an mRNA vaccine, Kranz et al further teaches adding a signal sequence to the mRNA of the vaccine in order to route to the ER and MHC class I transmembrane and cytoplasmic domains for improved presentation of MHC class I and II epitopes, and Kranz et al teaches targeting dendritic cells (DCs) with mRNA-lipid particle vaccines results in an adaptive and innate immune response.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA vaccines target and express the mRNA in dendritic cells (DCs), as taught by Kranz et al, because DCs are antigen presenting cells in lymphoid organs that are in close proximity to T cells that are involved in the immune response of the mRNA vaccines of the combined method.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating a subject with cancer comprising administering an anti-PD-1 antibody immunotherapeutic wherein the anti-PD-1 antibody immunotherapeutic is cemiplima (same as “REGN2810”) of Burova because Burova et al teaches the anti-PD-1 antibody cemiplima (same as “REGN2810”) as a cancer immunotherapeutic (Abstract, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of prophylactically or therapeutically treating a subject with cancer wherein the subject is classified according to RECIST 1.1 before and after treatment in order to provide the subject with an evaluation of the success of the treatment as compared to baseline because Eisenhauer et al teaches RECIST 1.1 to classify tumor burden in subjects (Abstract, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the poly(A) tails are modified to comprise sequences that have been modified to comprise more adenines because Islam et al teaches additional adenine residues confer stability to in vitro transcribed and capped mRNA and may increase its translational efficiency and, where direct comparisons have been made, longer poly(A) tails ˃adenine have generally been found to preferable to smaller ones (left column on page 1521, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA of the vaccine further encodes a tetanus toxoid CD4+ T cell epitope P2 peptide in an effort to improve the vaccine potential, enhance a CD8+ T cell and CD4+ T cell immune response, and result in adaptive immunity because Wen et al teaches tetanus toxoid universal CD4+ T cell epitope P2 expression improves cancer vaccine potential, resulting in higher neutralizing antibody titers (Abstract, in particular) and Williams et al teaches tetanus toxin P2 epitope as a highly immunogenic peptide that enhances tumor antigen specific immune response and provides T cell help to humoral immune responses targeting cell-surface antigens and enhance both CD8+ CTL and CD4+ th response, providing capacity for CD8+ T cell memory (left column on page 1636, in particular).
Further, of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA vaccine comprises, 5’ to 3’:
a 5’ cap of Valiante et al (known basic component of a typical mRNA molecule);
a 5’ UTR of Valiante et al (known basic component of a typical mRNA molecule);
an N-terminal signal peptide of Kreiter et al (increase antigen presentation);
a coding region encoding cancer antigen(s) of the mRNA vaccine of Besin et al;
tetanus toxoid P2 of Wen et al and Williams et al (increase immune response);
a MITD domain of Kranz et al and Kreiter et al (increase antigen presentation);
a 3’ UTR of Valiante et al (known basic component of a typical mRNA molecule); and
a poly-adenine tail of Valiante et al (known basic component of a typical mRNA molecule).
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 10-25, 35, 42, 72, 73, 75, 76, 78, and 84-87 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 54, 58-69, and 177-194 of copending Application No. 19/242465 in view of Cogdill et al (Surgery, 2012, 152: S13-8), Valiante et al (WO 2017/070618 A1; 4/27/17; 12/9/24 IDS), Kranz et al (Nature, 2016, (534): 396-401; 12/9/24 IDS), Burova et al (Mol Cancer Ther, 2017, 16(5): 861-870), Eisenhauer et al (European Journal of Cancer, 2009, 45: 228-247; 12/9/24 IDS), Islam et al (Biomater Sci, 2015, 3: 1519-1533), Kreiter et al (The Journal of Immunology, 2008, 180: 309-318; 12/9/24 IDS), Wen et al (Vaccine, 2014, 32(35): 4420-4427), and Williams et al (Cancer Immunol Immunother, 2008, 57: 1635-1645).
The instant claims and the copending claims are both drawn to treating subjects with cancer comprising administering mRNA vaccines and lipid. The instant claims differ from the copending claims due to additional recited mRNA components, MAGE-A3 as a target antigen, a recited step of administering an anti-PD-1 therapeutic, and other characteristics of recited subjects.
However, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method comprising performing a method of the copending claims comprising that of Valiante et al of treating a human subject comprising identifying any combination of cancer antigens for pancreatic cancer (such as MAGE-A3 of the Abstract of Cogdill in either the full-length wild-type or mutated form found in the subject) in a sample from subject with any cancer of Valiante et al, producing such a personalized cancer vaccine with mRNA of Valiante et al encoding the cancer antigens (“polyeptopic”) and administering the personalized cancer vaccine to the subject before (where there is evidence of disease at time for administration) or after tumor resection (where there is no evidence of disease at time for administration) optionally in combination with a cancer therapeutic agent, such as an anti-PD-1 antibody immunotherapeutic (such as nivolumab of Valiante et al), and measuring an immune response of Valiante et al in the subject as an indication the subject is therapeutically responding to the treatment because Valiante et al teaches subjects prophylactically and therapeutically respond to such treatments.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA has chemical modifications of Valiante et al (lines 8-11 on page 44, in particular) and perform said combined method wherein the mRNA does not have chemical modifications of Valiante et al (“natural ribonucleotides”) to determine whether such chemical modifications enhance therapeutic immunogenicity.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method using lipid particles of Kranz et al or Valiante et al wherein the mRNA vaccine further comprise mRNA encoding TPTE, signal sequence, and MHC class I transmembrane and cytoplasmic domains of Kranz et al and results in an adaptive immune response because Cogdill et al teaches MAGE-A3 as a cancer antigen, Kranz et al further teaches adding a signal sequence to the mRNA of the vaccine in order to route to the ER and MHC class I transmembrane and cytoplasmic domains for improved presentation of MHC class I and II epitopes, and Kranz et al teaches targeting dendritic cells (DCs) with mRNA-lipid particle vaccines results in an adaptive and innate immune response.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA vaccines target and express the mRNA in dendritic cells (DCs), as taught by Kranz et al, because DCs are antigen presenting cells in lymphoid organs that are in close proximity to T cells that are involved in the immune response of the mRNA vaccines of the combined method.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of treating a subject with cancer comprising administering an anti-PD-1 antibody immunotherapeutic wherein the anti-PD-1 antibody immunotherapeutic is cemiplima (same as “REGN2810”) of Burova because Burova et al teaches the anti-PD-1 antibody cemiplima (same as “REGN2810”) as a cancer immunotherapeutic (Abstract, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of prophylactically or therapeutically treating a subject with cancer wherein the subject is classified according to RECIST 1.1 before and after treatment in order to provide the subject with an evaluation of the success of the treatment as compared to baseline because Eisenhauer et al teaches RECIST 1.1 to classify tumor burden in subjects (Abstract, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the poly(A) tails are modified to comprise sequences that have been modified to comprise more adenines because Islam et al teaches additional adenine residues confer stability to in vitro transcribed and capped mRNA and may increase its translational efficiency and, where direct comparisons have been made, longer poly(A) tails ˃adenine have generally been found to preferable to smaller ones (left column on page 1521, in particular).
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method wherein the mRNA of the vaccine further encodes a tetanus toxoid CD4+ T cell epitope P2 peptide in an effort to improve the vaccine potential, enhance a CD8+ T cell and CD4+ T cell immune response, and result in adaptive immunity because Wen et al teaches tetanus toxoid universal CD4+ T cell epitope P2 expression improves cancer vaccine potential, resulting in higher neutralizing antibody titers (Abstract, in particular) and Williams et al teaches tetanus toxin P2 epitope as a highly immunogenic peptide that enhances tumor antigen specific immune response and provides T cell help to humoral immune responses targeting cell-surface antigens and enhance both CD8+ CTL and CD4+ th response, providing capacity for CD8+ T cell memory (left column on page 1636, in particular).
Further, of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein the mRNA vaccine comprises, 5’ to 3’:
a 5’ cap of Valiante et al (known basic component of a typical mRNA molecule);
a 5’ UTR of Valiante et al (known basic component of a typical mRNA molecule);
an N-terminal signal peptide of Kreiter et al (increase antigen presentation);
a coding region encoding cancer antigen(s) of the mRNA vaccine of Cogdill et al;
tetanus toxoid P2 of Wen et al and Williams et al (increase immune response);
a MITD domain of Kranz et al and Kreiter et al (increase antigen presentation);
a 3’ UTR of Valiante et al (known basic component of a typical mRNA molecule); and
a poly-adenine tail of Valiante et al (known basic component of a typical mRNA molecule).
This is a provisional nonstatutory double patenting rejection.
Conclusion
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