DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed 12/12/25 in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/12/25 has been entered.
Claim 12 has been amended.
Claims 1-10, 12-13, 16, 23-30 are pending.
Claims 1-10 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Claims 23-25 and 27-30 are withdrawn as being directed to non-elected species of costimulatory/ligand pairs or non-elected species of further nucleic acid species (the elected species of costimulatory/ligand and those rejoined are CTLA-4/B7.1, CD40/CD40L and OX40/OX40L and the elected species of further nucleic acid is a checkpoint inhibitor).
Claims 12-13, 16, and 26 are being acted upon.
Acknowledgment is made of applicant's claim for domestic priority under 35 U.S.C. 119(e). However, the provisional application USSN 62/429,990, upon which priority is claimed fails to provide adequate support under 35 U.S.C. 112 for the claims this application. Specifically, insufficient support was identified for the limitation of a recombinant nucleic acid comprising the specific elements of the claims, i.e. a costimulatory ligand and its receptor, an MHC-I and MHC-II polytope, at least one of a checkpoint inhibitor, a cell adhesion molecule, and a chimeric molecule. The ‘990 application also does not disclose the MHC-I and MHC-II polytope coupled together in concatemeric arrangement via a self-cleaving peptide. Consequently, the claims have been accorded the priority of the filing date of the PCT application, i.e. 11/20/17.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 12-13, 16, and 26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 12 is indefinite in the recitation that the MHC-I polytope and the MHC-II polytope are coupled together “in concatemeric arrangement” via a linker comprising a self-cleaving peptide. The specification does not define what is meant by “concatemeric arrangement” and the scope of the claims is unclear and indefinite. A “concatemer” is a term used in the art to define a continuous DNA molecule that consists of multiple copies of the same or substantially the same DNA sequence linked in series (See, for example, US 20220154215, paragraph 34, in particular). However, in the instant it is the MHC-I polytope and MHC-II polytope (i.e. different sequences) that are linked in “concatemeric” arrangement, and therefore the claims do not appear to require multiple copies of the same sequence. The specification does not define the term, but in paragraph 56 discloses an example where multiple neoepitopes were expressed from a single transcript that is translated into a single polytope (i.e. a polypeptide with a series of concatemerically linked neoepitopes, optionally with intervening linker sequences). In this example, the individual neoepitopes are concatemerically linked to form a single polytope transcript. Is the “concatemeric arrangement” limitation of the present claims intending to limit the nature of the epitopes that make up the MHC-I polytope, for example? The scope of the claims is unclear and indefinite. For the purpose of applying prior art, the limitation is being interpreted to encompass a single contiguous DNA molecule encoding the MHC-I polytope and MHC-II polytope linked via a self-cleaving peptide and expressed as a single transcript.
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 12-13, 16, and 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The specification and the claims as originally filed do not provide support for the invention as now claimed, specifically:
A nucleic acid encoding an MHC-I and MHC-II polytope, wherein the MHC-I polytope and the MHC-II polytope are coupled together “in concatemeric arrangement” via a linker comprising a self-cleaving peptide. (Claim 12, and dependent claims).
It is noted that applicant has not cited any support for the new limitation in the specification. A review of the specification fails to reveal support for the new limitations.
The specification in paragraph 56 discloses that multiple neoepitopes were expressed from a single transcript that is translated into a single polytope (i.e. a polypeptide with a series of concatemerically linked neoepitopes, optionally with intervening linker sequences). However, this example has a different scope than what is encompassed by the present claims. In the example in the specification, it is the individual neoepitopes of the polytope that are concatemerically linked. In contrast, in the present claims, the MHC-I polypeptide and MHC-II polytope are coupled in concatemeric arrangement. Furthermore, the present claims are not limited to concatemerically linked neoepitopes, as disclosed in the specification. Furthermore, the present claims also recite a concatemer arrangement via a “self-cleaving peptide” which is not disclosed in paragraph 56. The specification does not disclose a MHC-I and MHC-II polytope, wherein the MHC-I polytope and the MHC-II polytope are coupled together “in concatemeric arrangement” via a linker comprising a self-cleaving peptide, as now claimed.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim 12-13, 16, 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2008/0166367, in view of US 20110044953, WO00/63395, and US 2015/0258186 (all of record).
The ‘367 publication teaches a recombinant nucleic acid encoding multiple tumor specific antigens and costimulatory molecules (see page 2 and 7, in particular). The ‘367 publication also teaches including additional nucleic acids, such as those encoding antibodies (see page 13, in particular). The ‘367 publication teaches that the tumor antigens can be tailored to the individual patient (see page 13, in particular). The ‘367 publication teaches that the tumor antigens are selected such that proteins thereof will result in a MHC-I and II reaction with the intent to stimulate both CD4 and CD8 T cell responses, and teaches including more than one tumor antigen ( see page 5-6 and paragraphs 31 and 62, in particular). The ‘367 publication teaches that a recombinant viral vector infects APCs, including dendritic cells and the co-expression of both the antigen and immunostimulatory molecules provides the necessary MHC restricted peptide to specific T cells and the appropriate signal to the T cell to expand antigen specific T cells (see paragraph 107 and pages 23-24, in particular). The ’367 publication teaches wild type as well as mutated version of tumor antigens (i.e. neoepitopes, see page 6, in particular).
The ‘367 publication does not explicitly teach a chimeric protein comprising a costimulatory ligand and its receptor as the costimulatory molecule, a checkpoint inhibitor as the antibody, or that the multiple antigens are linked via self-cleaving peptide.
WO00/63395 teaches CD40L and CD40 act as costimulatory molecule to induce T cell immunity and APC activation (see page 1, in particular). WO00/6339 teach a recombinant nucleic acid sequence that encodes a TNF receptor family costimulatory ligand (CD40L) and a costimulatory receptor (CD40), wherein the nucleic acid is constructed such that they form a chimeric polypeptide (see pages 2-3 and 7, in particular). WO 00/63395 teaches that doing so is advantageous since it allows not only activation of the cell expressing the chimeric polypeptide, but an activating effect in trans in other cells that naturally express the receptors (see page 4, in particular). WO00/63395 teaches that the chimeric polypeptides are constructed using CD40L, a short linker or a spacer (i.e. a linker) wherein the spacer is flexible, and the CD40 region (see page 3 and Fig. 1, in particular). WO00/63395 also teaches that the linker must be of sufficient length, preferably between 15-30 amino acids, to ensure trimerization, i.e. it must be “flexible”, see page 3, in particular). WO00/63395 teaches that said CD40/CD40L chimera can be expressed with additional genes on the same vector, under the control of the same promoter (see page 6, in particular). For example, WO00/63395 teaches that more than one gene can be coupled via an IRES sequence (i.e. configured for translation from a single transcript, see page 15-16, in particular. WO00/63395 teaches adenoviral vectors (see page 16-17, in particular). WO00/63395 teaches that the invention makes it possible to induce the presentation of tumor specific antigens on immunocompetent cells in an improved manner and to induce differentiation and proliferation of T cells and dendritic cells (i.e. APCs, see page 4, in particular).
The ‘953 publication teaches viral vectors comprising a nucleic acid encoding an anti-CTLA-4 antibody that blocks CTLA-4 signaling (i.e. a checkpoint inhibitor). The ‘953 publication teaches using said viral vectors to modifying antigen presenting cells, such as dendritic cells, in order to enhance T cell activation and treat tumors (see page 1 and 3, in particular).
The ‘186 publication teaches a viral vector, such as an adenovirus, allowing expression of multiple tumor antigens for administration to a subject to provide an effective immune response for treating cancer (see pages 1-2 and 8, and paragraph 42, in particular). The ‘186 publication teaches that the plurality of antigens include HLA-class I and HLA-class II epitopes (see page 9, in particular). The ‘186 publication teaches that the plurality of antigen are separated by a cleavage site, such as a self-cleaving P2A peptide (see page 9, in particular). The ‘186 publication explains that the antigens may have two or more copies of the antigens, and that the construct is encoded as a single transcript comprising a plurality of MHC-I and MHC class II antigen peptides (i.e. polytopes) expressed as a linear single polypeptide, wherein each antigen is separated by a self-cleaving peptide (i.e. , see paragraph 81, in particular). The ‘186 publication teaches that the antigens represent an advantageous, efficient and manageable vaccine (see page 1, in particular). The ‘186 publication teaches that the nucleic acids provide a safe and long lasting protective immunity and allows for rapid identification and selection of relevant nucleic acid based vaccines for cancer (See pages 10-11, in particular). The ‘186 publication teaches that the antigen are advantageous since they are capable of stimulating HLA-Class I and Class II restricted T cells (see page 14, in particular). The ‘186 publication teaches that additional immune stimulatory or modulating agents including check point inhibitors may be included (See paragraph 131, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to construct the recombinant nucleic acid of the ‘367 publication, using a nucleic acid encoding a chimeric costimulatory polypeptide as taught by WO00/63395 as the costimulatory molecule, using the nucleic acid encoding the CTLA-4 antibody of the ‘953 publication as the antibody, and using a nucleic acid encoding the multi-antigen construct of the ‘186 publication, as the multiple antigens in the construct of the ‘367 publication.
The ordinary artisan would be motivated use the chimeric costimulatory polypeptide of WO 00/63395 as the costimulatory molecule in the nucleic acid construct of the’367 publication, since WO 00/63395 teaches that is advantageous because it allows not only activation of the cell expressing the chimeric polypeptide, but an activating effect in trans in other cells that naturally express the receptors thus making it possible induce the presentation of tumor specific antigens on immunocompetent cells in an improved manner and to induce differentiation and proliferation of T cells and dendritic cells.
One of ordinary skill in the art at the time the invention was made would be motivated to include a nucleic acid encoding the anti-CTLA-4 antibody of the ‘953 publication, as the type of additional nucleic acid encoding an antibody in the viral vector of the ‘367 publication, since the ‘953 publication teaches that viral vectors encoding anti-CTLA-4 can be used to enhance T cell activation and treat tumors.
Furthermore, the ordinary artisan would be motived to use the multiple tumor antigen nucleic acids comprising a plurality of HLA-class I and class II peptides separated by P2A cleavage sites, as taught by the ‘186 publication with a reasonable expectation of success, because the ‘186 publication teaches that the antigens represent an advantageous, efficient and manageable vaccine. Additionally, the ‘186 publication teaches that the nucleic acids provide a safe and long lasting protective immunity and allows for rapid identification and selection of relevant nucleic acid based vaccines for cancer and that the antigens are advantageous since they are capable of stimulating HLA-Class I and Class II restricted T cells.
It would also be obvious to construct the nucleic acids encoding each element from a single promoter, such as using an IRES, as taught by WO00/63395, i.e. from a single transcript. Doing so, as well as selecting from known viral vectors including adenovirus would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385).
Applicant’s arguments filed 12/12/25 have been fully considered, but they are not persuasive.
Applicant argues that the claims require a chimeric molecule that comprises a targeting portion binding specifically to a component of a necrotic cell and that is configured to enhance selective immune cell recruitment or activation at necrotic sites, which is not taught in the cited references.
Claim 12 is directed to a recombinant nucleic acid comprising a nucleic acid sequence that encodes “at least one of” a checkpoint inhibitor, a cell adhesion molecules, and a chimeric molecule. The amendment in the last two lines of the claim regarding enhanced selective immune cell recruitment and activation at necrotic sites defines features of the chimeric molecule, but the chimeric molecule is not a required element in the claim. Thus, in contrast to Applicant’s assertions the claims do no require a chimeric molecule, and encompass a checkpoint inhibitor, as the “at least one” element listed in lines 6-8 of claim 12, and as made obvious in the prior art rejection above.
Claim 12-13, 16, 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2005/026370, in view of US 20110044953, US2015/0258186 and WO00/63395 (all of record).
WO 2005/026370 teaches a method of treating cancer comprising administering to a patient a vector comprising a recombinant nucleic acid encoding multiple tumor specific antigens and a costimulatory molecule (see page 2 and 15, in particular). WO 2005/026370 teaches CD40L as a type of costimulatory molecule (see page 15-16, in particular). WO 2005/026370 teaches expression of the tumor antigen following administration leads to an anti-cancer T cell immune response (see pages 2-3, in particular). WO 2005/026370 teaches wild type as well as mutated version of tumor antigens (i.e. neoepitopes, see page 4, in particular). WO20150258186 also teaches further administration of anti-CTLA-4 (i.e. a checkpoint inhibitor antibody) to suppress negative regulatory mechanism (see page 17, in particular). WO 2005/026370 teaches using viral vectors, such as adenovirus (i.e. vectors are expressed in APC, see page 19, in particular). WO 2005/026370 teaches induction of T cell and CTL response and examples of using a nucleic acid encoding multiple tumor antigens (see pages 27-29). WO 2005/026370 teaches that the co-stimulatory component may be included as a nucleic acid, and teaches nucleic acids may be delivered in viral vectors (see pages 15 and 19-20, in particular). WO 2005/026370 exemplifies a viral vector encoding said multiple tumor antigens and costimulatory molecules in a single nucleic acid vector sequence (see pages 27-28 and Fig. 1, in particular).
WO 2005/026370 does not explicitly teach a chimeric protein comprising a costimulatory ligand and its receptor as the costimulatory molecule, a checkpoint inhibitor, or that the multiple antigens are linked via self-cleaving peptide.
The ‘953 publication teaches viral vectors comprising a nucleic acid encoding an anti-CTLA-4 antibody that blocks CTLA-4 signaling (i.e. a checkpoint inhibitor). The ‘953 publication teaches using said viral vectors to modifying antigen presenting cells, such as dendritic cells, in order to enhance T cell activation and treat tumors (see page 1 and 3, in particular). The ‘953 publication teaches that it is advantageous since it provides localized delivery of the antibody and increases the intensity and duration of T cell responses (see pages 1and 3, in particular). The ‘953 publication teaches anti-CTLA-4 according to US 5,855,887 (i.e. ipilimumab).
WO00/63395 teaches CD40L and CD40 act as costimulatory molecule to induce T cell immunity and APC activation (see page 1, in particular). WO00/6339 teach a recombinant nucleic acid sequence that encodes a TNF receptor family costimulatory ligand (CD40L) and a costimulatory receptor (CD40), wherein the nucleic acid is constructed such that they form a chimeric polypeptide (see pages 2-3 and 7, in particular). WO 00/63395 teaches that doing so is advantageous since it allows not only activation of the cell expressing the chimeric polypeptide, but an activating effect in trans in other cells that naturally express the receptors (see page 4, in particular). WO00/63395 teaches that the chimeric polypeptides are constructed using CD40L, a short linker of 1 to 30 amino acids, and the CD40 region, thus rendering obvious linkers of the size recited in claim 22 (see page 3 and Fig. 1, in particular). WO00/63395 teaches that said CD40/CD40L chimera can be expressed with additional genes on the same vector, under the control of the same promoter (see page 6, in particular). For example, WO00/63395 teaches that more than one gene can be coupled via an IRES sequence (i.e. configured for translation from a single transcript, see page 15-16, in particular. WO00/63395 teaches adenoviral vectors (see page 16-17, in particular). WO00/63395 teaches that the invention makes it possible to induce the presentation of tumor specific antigens on immunocompetent cells in an improved manner and to induce differentiation and proliferation of T cells and dendritic cells (i.e. APCs, see page 4, in particular).
The ‘186 publication teaches a viral vector, such as an adenovirus, allowing expression of multiple tumor antigens for administration to a subject to provide an effective immune response for treating cancer (see pages 1-2 and 8, and paragraph 42, in particular). The ‘186 publication teaches that the plurality of antigens include HLA-class I and HLA-class II epitopes (see page 9, in particular). The ‘186 publication teaches that the plurality of antigen are separated by a cleavage site, such as a self-cleaving P2A peptide (see page 9, in particular). The ‘186 publication explains that the antigens may have two or more copies of the antigens, and that the construct is encoded as a single transcript comprising a plurality of MHC-I and MHC class II antigen peptides (i.e. polytopes) expressed as a linear single polypeptide, wherein each antigen is separated by a self-cleaving peptide (i.e. , see paragraph 81, in particular). The ‘186 publication teaches that the antigens represent an advantageous, efficient and manageable vaccine (see page 1, in particular). The ‘186 publication teaches that the nucleic acids provide a safe and long lasting protective immunity and allows for rapid identification and selection of relevant nucleic acid based vaccines for cancer (See pages 10-11, in particular). The ‘186 publication teaches that the antigen are advantageous since they are capable of stimulating HLA-Class I and Class II restricted T cells (see page 14, in particular). The ‘186 publication teaches that additional immune stimulatory or modulating agents including check point inhibitors may be included (See paragraph 131, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use the chimeric costimulatory polypeptide as of WO00/63395, as the costimulatory molecule in the recombinant nucleic acid of WO 2005/026370, to use the multi-antigen construct of the ‘186 publication as the multiple antigens in the recombinant nucleic acid of WO 2005/026370, and to include a nucleic acid encoding the CTLA-4 antibody as taught by the ‘953 publication.
The ordinary artisan would be motivated to include a nucleic acid encoding anti-CTLA-4 antibody as taught by the ‘953 publication, in the multi-expression vector of WO 2005/026370, to provide for anti-CTLA-4 blocking of inhibitor immune mechanism as taught in WO2005/026370. The ordinary artisan at the time the invention was made would have been motivated to do so since the ‘953 publication teaches that it is advantageous since it provides localized delivery of the antibody and increases the intensity and duration of T cell responses
Furthermore, the ordinary artisan would be motivated to construct the recombinant nucleic acid encoding CD40L in WO2005/026370, using the chimeric CD40L/CD40, as taught by WO00/63395, since WO 00/63395 teaches that it is advantageous because it allows not only activation of the cell expressing the chimeric polypeptide, but an activating effect in trans in other cells that naturally express the receptors.
Furthermore, it would be it have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to construct the recombinant nucleic acid encoding multiple tumor antigens of WO 2005/026370, using the multiple tumor antigen nucleic acids comprising a plurality of HLA-class I and class II peptides separated by P2A cleavage sites, as taught by the ‘186 publication. The ordinary artisan would have been motivated to do so with a reasonable expectation of success because the ‘186 publication teaches that the antigens represent an advantageous, efficient and manageable vaccine. Additionally, the ‘186 publication teaches that the nucleic acids provide a safe and long lasting protective immunity and allows for rapid identification and selection of relevant nucleic acid based vaccines for cancer and that the antigens are advantageous since they are capable of stimulating HLA-Class I and Class II restricted T cells.
It would also be obvious to construct the nucleic acids encoding each element from a single promoter, such as using an IRES, as taught by WO00/63395. Doing so, as well as selecting from known viral vectors including adenovirus would involve choosing among a finite number of predictable options which could be pursued with a reasonable expectation of success. A person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense (see KSR International Co. V. Telefex Inc 82 USPQ2d 1385).
Applicant argues that the claims are not obvious for the reasons set forth above.
The claims stand rejected for the same reasons set forth above.
Claim 12-13, 16, 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2017/0028044 or US 2017/0312351, in view of US 20110044953 (of record) and WO00/63395 (of record).
The ‘044 publication teaches a recombinant nucleic acid adenovirus vector comprising a nucleic acid encoding multiple tumor neoepitope antigens, a costimulatory molecule and a checkpoint inhibitor (See paragraphs 12-15 and 29 in particular). The ‘044 publication teaches that the neoepitopes can have a concatemeric arrangement of multiple MHC-I and MHC-II epitopes representing polytopes, and that they are separated by protease cleavable linkers (see paragraph 66, 68, and 70, in particular). The ‘044 publication teaches CD40 and CD40L as costimulatory molecules, and that the elements are produced from a single transcript using an IRES or 2A sequence (See paragraph 73-74, in particular). The teachings of the ‘351 publication are nearly identical to that of the ‘044 publication, and the ‘351 publication also teaches a recombinant nucleic acid adenovirus vector comprising a nucleic acid encoding multiple tumor neoepitope antigens, a costimulatory molecule and a checkpoint inhibitor, wherein the neoepitopes can have a concatemeric arrangement of multiple MHC-I and MHC-II epitopes representing polytopes, and wherein the costimulatory molecules are CD40 and CD40L.
The ‘044 and ‘351 publications do not explicitly teach a chimeric protein comprising a costimulatory ligand and its receptor as the costimulatory molecule, or that they neoepitopes are linked via self-cleaving peptide.
WO00/63395 teaches CD40L and CD40 act as costimulatory molecule to induce T cell immunity and APC activation (see page 1, in particular). WO00/6339 teach a recombinant nucleic acid sequence that encodes a TNF receptor family costimulatory ligand (CD40L) and a costimulatory receptor (CD40), wherein the nucleic acid is constructed such that they form a chimeric polypeptide (see pages 2-3 and 7, in particular). WO 00/63395 teaches that doing so is advantageous since it allows not only activation of the cell expressing the chimeric polypeptide, but an activating effect in trans in other cells that naturally express the receptors (see page 4, in particular). WO00/63395 teaches that the chimeric polypeptides are constructed using CD40L, a short linker or a spacer (i.e. a linker) wherein the spacer is flexible, and the CD40 region (see page 3 and Fig. 1, in particular). WO00/63395 also teaches that the linker must be of sufficient length, preferably between 15-30 amino acids, to ensure trimerization, i.e. it must be “flexible”, see page 3, in particular). WO00/63395 teaches that said CD40/CD40L chimera can be expressed with additional genes on the same vector, under the control of the same promoter (see page 6, in particular). For example, WO00/63395 teaches that more than one gene can be coupled via an IRES sequence (i.e. configured for translation from a single transcript, see page 15-16, in particular. WO00/63395 teaches adenoviral vectors (see page 16-17, in particular). WO00/63395 teaches that the invention makes it possible to induce the presentation of tumor specific antigens on immunocompetent cells in an improved manner and to induce differentiation and proliferation of T cells and dendritic cells (i.e. APCs, see page 4, in particular).
The ‘186 publication teaches a viral vector, such as an adenovirus, allowing expression of multiple tumor antigens for administration to a subject to provide an effective immune response for treating cancer (see pages 1-2 and 8, and paragraph 42, in particular). The ‘186 publication teaches that the plurality of antigens include HLA-class I and HLA-class II epitopes (see page 9, in particular). The ‘186 publication teaches that the plurality of antigen are separated by a cleavage site, such as a self-cleaving P2A peptide (see page 9, in particular). The ‘186 publication explains that the antigens may have two or more copies of the antigens, and that the construct is encoded as a single transcript comprising a plurality of MHC-I and MHC class II antigen peptides (i.e. polytopes) expressed as a linear single polypeptide, wherein each antigen is separated by a self-cleaving peptide (i.e. , see paragraph 81, in particular). The ‘186 publication teaches that the antigens represent an advantageous, efficient and manageable vaccine (see page 1, in particular). The ‘186 publication teaches that the nucleic acids provide a safe and long lasting protective immunity and allows for rapid identification and selection of relevant nucleic acid based vaccines for cancer (See pages 10-11, in particular). The ‘186 publication teaches that the antigen are advantageous since they are capable of stimulating HLA-Class I and Class II restricted T cells (see page 14, in particular). The ‘186 publication teaches that additional immune stimulatory or modulating agents including check point inhibitors may be included (See paragraph 131, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to construct the recombinant nucleic acid of the ‘044 publication or ‘351 publication, using a nucleic acid encoding a chimeric costimulatory polypeptide as taught by WO00/63395 as the costimulatory molecule, and using a self-cleaving peptide, as taught by the ‘186 publication, as the protease cleavable linker
The ordinary artisan would be motivated use the chimeric costimulatory polypeptide of WO 00/63395 as the costimulatory molecule, since WO 00/63395 teaches that is advantageous because it allows not only activation of the cell expressing the chimeric polypeptide, but an activating effect in trans in other cells that naturally express the receptors thus making it possible induce the presentation of tumor specific antigens on immunocompetent cells in an improved manner and to induce differentiation and proliferation of T cells and dendritic cells.
Furthermore, the ordinary artisan would be motived to use the multiple tumor antigen nucleic acids comprising a plurality of HLA-class I and class II peptides separated by P2A cleavage sites, as taught by the ‘186 publication with a reasonable expectation of success, because the ‘186 publication teaches that the antigens represent an advantageous, efficient and manageable vaccine. Additionally, the ‘186 publication teaches that the nucleic acids provide a safe and long lasting protective immunity and allows for rapid identification and selection of relevant nucleic acid based vaccines for cancer and that the antigens are advantageous since they are capable of stimulating HLA-Class I and Class II restricted T cells.
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 12-13, 16, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,623,001. in view of US 2008/0166367, WO00/63395, and US 2015/0258186.
The ‘001 patent claims a recombinant nucleic acid sequence consisting of a promoter operably coupled to a nucleic acid sequence encoding a plurality of neoepitopes that are directed to presentation by at least one class I molecule or at least one class II molecule for treating a tumor, wherein the recombinant nucleic acid is a viral expression vector, and wherein the recombinant nucleic acid further comprises at least one sequence encoding a co-stimulator molecule and a sequence encoding a checkpoint inhibitor. It would be obvious to use the chimeric costimulatory molecule of WO 00/633395 as the type of costimulatory molecule, and to use the multi-antigen construct of the ‘186 publication as the plurality of neoepitopes for the same reasons set forth above.
Claims 12-13, 16, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 11 of U.S. Patent No. 12,491,160 or 11,229,668, in view of US 2008/0166367, WO00/63395, and US 2015/0258186.
The patents claim a recombinant nucleic acid that encodes a least one cancer epitope or neoepitope, a checkpoint inhibitor, and a co-stimulatory molecule. The ‘160 patent claims that the recombinant nucleic acid is a adenovirus vector. It would be obvious to use the chimeric costimulatory molecule of WO 00/633395 as the type of costimulatory molecule, and to use the multi-antigen construct of the ‘186 publication as the type of cancer antigen for the same reasons set forth above.
No claim is allowed.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644