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 .
Election/Restrictions
Applicant's election without traverse of invention Group I, claims 1-17, of the IAP species ‘CprI’, and of the composition species ‘polynucleotide encoding IAP’, in the reply filed on 01/07/2026 is acknowledged. Applicant further elected with traverse the species ‘Toll like receptor (TLR) agonist’ as the additional component encoded by an IAP encoding polynucleotide’. Applicant timely traversed the restriction (election) requirement in the
reply filed on 01/07/2026.
In Applicant’s reply, Applicant states that “there should be no additional requirement to elect a species of "additional component" encoded by the polynucleotide as requested in the group of species enumerated in item 3) of the species election requirement because the other proposed species are not required to be encoded by the polynucleotide according to the original
claims, i.e., the other species may be administered separately.” (election, page 2).
The Examiner responds that, according to instant claim 7, the claimed polynucleotide of the invention further encodes the following species: a Toll Like receptor (TLR) agonist, a cancer antigen, a binding partner that binds with specificity to a dendritic cell surface marker, a binding partner that binds with specificity to a cancer cell surface marker, or a combination thereof. These species are deemed to lack unity of invention because they are not so linked as to form a single general inventive concept under PCT Rule 13.1. The recited species are independent and distinct because they are different proteins with different structures and biological properties, and therefore have differing effects on stimulating an immune response. It is further noted that the additional components encoded by the polynucleotide result in different polynucleotide species which have different structures and biological properties.
Upon the allowance of a generic claim, Applicant will be entitled to consideration of claims to additional species which are written in dependent form or otherwise require all the limitations of an allowed generic claim.
In conclusion, Applicant’s arguments are not persuasive. The requirement is still deemed proper and is therefore made FINAL.
Claim Status
Claims 1-23 are pending (claim set as filed on 07/10/2023). Claims 4-6, 8-9, and 14-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/07/2026.
Claims 1-3, 7, and 10-13, are currently under examination and were examined on their merits
Priority
This application filed on 07/10/2023 claims priority to PCT application no. PCT/US2022/012167, filed on 01/12/2022, and claims priority to provisional application no. PRO 63/136,311, filed on 01/12/2021.
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 07/10/2023 has been received and considered.
Claim Rejections - 35 USC § 112 (b)
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.
Claim 3 is 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 3 recites “the fusion protein” which is indefinite for lacking antecedent basis because ‘fusion protein’ is not recited within the claim or in base claim 1 from which claim 3 depends. One of ordinary skill in the art would not be able to determine the metes and bounds of the claim, and thus, could not clearly determine how to avoid infringement of claim 3.
In the interest of compact prosecution, claim 3 is interpreted to the broadest embodiment claimed.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nilles (US 2014/0120128 A1, published on 05/01/2014), hereinafter ‘Nilles’.
Nilles’ general disclosure relates to “compositions and methods for enhancing an immune response by providing an adjuvant of isolated or recombinant YscF, an isolated or
recombinant fragment or truncation thereof, or a homolog thereof” (see entire document, including paragraph [0002]).
Regarding claim 1, pertaining to the method, Nilles teaches a method comprising introducing an Inflammasome Agonist Protein (IAP) that is a Needle protein into an individual in need thereof to thereby stimulate an immune response in the individual (paragraphs [0011]-[0012]; see abstract). It is noted that Nilles’ YscF, PrgI MxiH and SsaG are needle proteins (Nilles, paragraph [0005], [0074]; instant specification, paragraph [0057]).
Regarding claim 2, pertaining to the IAP, Nilles teaches wherein i) the IAP is a component of a fusion protein (paragraph [0071]).
Regarding claim 10, pertaining to the IAP, Nilles teaches wherein the IAP is PrgI or SsaG (paragraphs [0008], [0074]).
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.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Nilles (US 2014/0120128 A1, published on 05/01/2014), hereinafter ‘Nilles’.
Nilles’ teachings have been set forth above.
Regarding claim 3, pertaining to the method, please note the rejection under Claim Rejections- 35 USC § 112 (b) above.
Pertaining to the Toll Like Receptor (TLR) agonist, Nilles teaches the TLR agonist flagellin (paragraph [0090]), and further teaches wherein both flagellin and the needle protein YscF individually induce an immune response in macrophages and THP-1 cells (paragraphs [0107] and [0108]; see Figures 15 and 16).
In addition, Nilles teaches an antigenic composition comprising the needle protein YscF or an YscF homolog combined with antigens or other adjuvants (paragraph [0071]).
Nilles does not teach wherein a Toll Like Receptor (TLR) agonist is also administered to the individual (instant claim 3).
While Nilles does not teach wherein a Toll Like Receptor (TLR) agonist is also
administered to the individual (instant claim 3), it would have been obvious to have combined Nilles method with Nilles teachings on the TLR5 agonist flagellin, to have created a method for inducing an immune response wherein a Toll Like Receptor (TLR) agonist is also administered to the individual. One would have been motivated to do so in order to improve the induced immune response since both, the Needle protein YscF and flagellin, individually induce an immune response (Nilles, paragraphs [0107] and [0108]; see Figures 15 and 16). A skilled artisan would have reasonable expected success in combining Nilles method with Nilles TLR agonist flagellin since Nilles teaches combining the needle protein YscF with other adjuvants (paragraph [0071]).
Claims 1-2 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Nilles (US 2014/0120128 A1, published on 05/01/2014), hereinafter ‘Nilles’, in view of Kedl et al. (US 2009/0004194 A1, published on 01/01/2009), hereinafter ‘Kedl’, as evidenced by Li et al. (“Molecular mechanisms for enhanced DNA vaccine immunogenicity”, published on 12/28/2015, Expert Review of Vaccines, Vol. 15, No. 3, pages 313-329), hereinafter ‘Li’.
Nilles’ teachings have been set forth above.
Regarding claims 2 and 7, please note the elected composition species ‘polynucleotide encoding IAP’ as composition species for introducing IAP into an individual under Election/Restrictions above.
Regarding claim 2, pertaining to the method, Nilles teaches wherein ii) the IAP is encoded by a polynucleotide (paragraph [0010]; see abstract).
In addition, Nilles further teaches wherein the IAP is expressed within a host cell ([0010]; see abstract).
Regarding claim 7, pertaining to the elected Toll Like Receptor (TLR) agonist, Nilles teaches the TLR agonist flagellin (paragraph [0090]), and further teaches wherein both flagellin and the needle protein YscF individually induce an immune response in macrophages and THP-1 cells (paragraphs [0107] and [0108]; see Figures 15 and 16).
In addition, Nilles teaches an antigenic composition comprising the needle protein YscF or an YscF homolog combined with antigens or other adjuvants (paragraph [0071]).
Nilles does not teach wherein ii) the IAP is encoded by a polynucleotide that is introduced into cells of the individual such that the IAP is expressed within the cells (instant claim 2), and wherein the polynucleotide further encodes a Toll Like Receptor (TLR) agonist (instant claim 7).
Kedl’s general disclosure relates to fusion proteins and DNA conjugates which contain a TLR/CD40/agonist and optional antigen combination (see entire document, including abstract).
Regarding claim 2, pertaining to the polynucleotide, Kedl teaches a polynucleotide encoding two agonists, the polynucleotide being administered to an individual to induce an immune response (paragraphs [0037], [0061], [0125]; see claims 1 and 36), wherein the polynucleotide is used as a DNA based vaccine (paragraphs [0061], [0125]). It is noted that DNA vaccines are introduced into cells where the DNA is expressed, as evidenced by Li et al. (page 313, left column, paragraph 1; page 318, left column, paragraph 1).
Regarding claim 7, pertaining to the polynucleotide, Kedl teaches wherein the polynucleotide further encodes a Toll Like receptor (TLR) agonist (see claim 1).
In addition, Kedl teaches wherein a polynucleotide encoding two agonists elicits a synergistic effect on immunity (paragraph [0018]).
While Nilles does not teach ii) wherein the IAP is encoded by a polynucleotide that is introduced into cells of the individual such that the IAP is expressed within the cells (instant claim 2), and wherein the polynucleotide further encodes a Toll Like Receptor (TLR) agonist (instant claim 7), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined Nilles’ method using a Needle protein to induce an immune response with Kedl’s teachings on a polynucleotide encoding two agonists including a TLR agonist, to have created a method wherein the IAP is encoded by a polynucleotide that is introduced into cells of the individual such that the IAP is expressed within the cells, and wherein the polynucleotide further encodes a Toll Like Receptor (TLR) agonist. One would have been motivated to do so to induce an increased immune response since Kedl teaches wherein a polynucleotide encoding two agonists elicits a synergistic effect on immunity (paragraph [0018]). A skilled artisan would have reasonably expected success in combining Nilles’ with Kedl’s teachings since both are directed to inducing immune responses.
Claims 1, 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Nilles (US 2014/0120128 A1, published on 05/01/2014), hereinafter ‘Nilles’, in view of Yang et al. (“Human NAIP and mouse NAIP1 recognize bacterial type III secretion needle protein for inflammasome activation”, published on 08/27/2013, PNAS, Vol. 110, No. 35, pages 14408-14413; supporting information pages 1-20), hereinafter ‘Yang’.
Nilles’ teachings have been set forth above.
Regarding claim 11, pertaining to the Toll Like Receptor (TLR) agonist, Nilles teaches the TLR agonist flagellin (paragraph [0090]), and further teaches wherein both flagellin and the needle protein YscF individually induce an immune response in macrophages and THP-1 cells (paragraphs [0107] and [0108]; see Figures 15 and 16).
In addition, Nilles teaches an antigenic composition comprising a needle protein combined with antigens or other adjuvants (paragraph [0071]).
Nilles does not teach wherein the IAP is the elected Cprl (instant claim 10; please note the elected IAP species ‘CprI’ under Election/Restrictions above). Nilles does not teach wherein a TLR agonist is introduced into the individual, and wherein the TLR agonist comprises flagellin or a TLR5-binding flagellin derivative (instant claim 11).
Yang’s general disclosure relates to Inflammasome mediated by central nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) protein, and that type III
secretion system (T3SS) needle proteins from several bacterial pathogens can induce robust inflammasome activation (see entire document, including abstract).
Regarding claim 10, pertaining to CprI, Yang teaches the needle protein CprI (page 14408, right column, paragraph 2), and that CprI acts as an inflammasome agonist (page 14408, right column, paragraph 2; page 14409, left column, paragraph 2; page 14411, right column, paragraph 2 - page 14412, left column, paragraph 1; see Fig. 1 A-D and Fig. S8 A-C).
Yang further suggests the use of needle proteins in vaccine development (see text box on page 14408).
While Nilles does not teach wherein the IAP is the elected Cprl (instant claim 10), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have modified Nilles’ method for inducing an immune response with Yang’s teachings on CprI, in order to create a method for inducing an immune response wherein the IAP is CprI. One would have been motivated to do so to improve the induced immune response since Yang teaches wherein CprI stimulates inflammasome activation (page 14408, right column, paragraphs 2-3). A skilled artisan would have reasonably expected success in combining Nilles’ and Yang’s teachings since both are directed to needle proteins for inducing immune responses.
While modified Nilles does not teach wherein a TLR agonist is introduced into the individual, and wherein the TLR agonist comprises flagellin or a TLR5-binding flagellin derivative (instant claim 11), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have combined modified Nilles’ method with Nilles teachings on the TLR agonist flagellin, to have created a method wherein a TLR agonist is introduced into the individual, and wherein the TLR agonist comprises flagellin. One would have been motivated to do so in order to further improve the induced immune response since both the Needle protein CprI and flagellin induce immune responses (Yang, page 14408, right column, paragraph 2, see Fig. 1 and Fig. S8; Nilles, paragraphs [0107] and [0108], see Figures 15 and 16), and since Nilles teaches combining a needle protein with other adjuvants (paragraph [0071]).
Claims 1, 10, and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Nilles (US 2014/0120128 A1, published on 05/01/2014), hereinafter ‘Nilles’, in view of Yang et al. (“Human NAIP and mouse NAIP1 recognize bacterial type III secretion needle protein for inflammasome activation”, published on 08/27/2013, PNAS, Vol. 110, No. 35, pages 14408-14413; supporting information pages 1-20), hereinafter ‘Yang’, and in view of Blander et al. (US 2015/0064219 A1, published on 03/05/2015), hereinafter ‘Blander’.
Nilles and Yang’s teachings have been set forth above.
Regarding claims 12-13, please note the elected IAP species ‘CprI’ under Election/Restrictions above.
Regarding claim 12, pertaining to CprI, Yang teaches wherein the elected IAP CprI is introduced into dendritic cells (page 14411, right column, paragraph 2 - page 14412, left column, paragraph 1; see Fig. S8 B).
In addition, Yang teaches that “hNAIP and its mouse ortholog NAIP1 are responsible for
recognizing cytosolic T3SS needle proteins” (page 14408, right column, paragraphs 3), and that NAIPs are a family of NRL (Nod like receptors) (page 14408, right column, paragraph 2). Yang further discloses that CprI acts as an inflammasome agonist in dendritic cells (page 14411, right column, paragraph 2 -page 14412, left column, paragraph 1; see Fig. S8 B-C).
Modified Nilles does not teach wherein the IAP is introduced into dendritic cells that activate T cells that participate in inhibiting growth of and/or killing cancer cells that express a cancer antigen (instant claim 12), and wherein the T cells are CD8+ T cells (instant claim 13).
Blander’s general disclosure relates to methods for inducing an anti-tumor immune response by immunizing a mammal with a composition comprising a tumor cell which expresses a Nod-like receptor (NLR) and/or a Toll-like receptor (TLR) ligand-tumor associated antigen (TAA) fusion protein or with an activated DC which has internalized a tumor cell which expresses an NLR- and/or TLR ligand-TAA fusion protein (see entire document, including abstract).
Regarding claim 12, pertaining to a dendritic cell, Blander teaches introducing a Nod-like receptor (NLR) ligand into dendritic cells (paragraphs [0059]-[0061]; claims 1 and 7) that activate T cells that participate in killing cancer cells (paragraphs [0095], [0016]) that express a cancer antigen (paragraph [0103]).
Regarding claim 13, pertaining to the T cells, Blander teaches wherein the T cells are CD8+ cells (paragraph [0095]).
In addition, Blander teaches NAIP as Nod-like receptor (NLR) (paragraph [0006]), and NLR based activation of immune response (paragraph [0010]).
While modified Nilles does not teach wherein the IAP is introduced into dendritic cells that activate T cells that participate in inhibiting growth of and/or killing cancer cells that express a cancer antigen (instant claim 12), and wherein the T cells are CD8+ T cells (instant claim 13), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to have combined modified Nilles method with Blander’s teachings on using dendritic cells comprising NRL ligands for killing cancer cells, in order to create a method wherein the elected IAP CprI is introduced into dendritic cells that activate T cells that participate in inhibiting growth of and/or killing cancer cells that express a cancer antigen, and wherein the T cells are CD8+ T cells. One would have been motivated to do so in order to induce an increased immune response in an individual for improved cancer treatment. A skilled artisan would have reasonably expected success in combining modified Nilles’ with Blander’s teachings since both are directed to inducing immune responses involving Nod-like receptors (Yang, page 14411, right column, paragraph 2 - page 14412, left column, paragraph 1; Blander, paragraphs [0006], [0010], [0024], see abstract).
Conclusion
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SANDRA ZINGARELLI whose telephone number is (703)756-1799. The examiner can normally be reached M-F 9-5.
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/SANDRA ZINGARELLI/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/ Supervisory Patent Examiner, Art Unit 1653
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