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 .
Applicants’ Amendment
1) Acknowledgment is made of Applicants’ amendment filed 04/21/2025 in response to the non-final Office Action mailed 12/19/24.
Status of Claims
2) Claims 1, 3, 6 and 8 are amended via the amendment filed 04/21/2025.
Claims 1-20 are pending.
Claims 1-8 are under examination.
Prior Citation of Title 35 Sections
3) The text of those sections of Title 35 U.S. Code not included in this action can be found in a prior Office Action References.
Prior Citation of References
4) The references cited or used as prior art in support of one or more rejections in the instant Office Action and not included on an attached form PTO-892 or form PTO-1449 have been previously cited and made of record.
Objection(s) Withdrawn
5) The objection to the specification set forth in paragraph 8 of the Office Action mailed 12/19/24 is withdrawn in light of Applicants’ amendments to the specification.
6) The objection to claims 1 and 3 set forth in paragraph 23 of the Office Action mailed 12/19/24 is withdrawn in light of Applicants’ claim amendment.
Rejection(s) Withdrawn
7) The rejection of claims 1-8 set forth in paragraph 10 of the Office Action mailed 12/19/24 under 35 U.S.C § 112(a) or 35 U.S.C § 112 (pre-AIA ), first paragraph, with regard to the written description issue is withdrawn in light of Applicants’ claim amendments. A new rejection is set forth below in this Office Action to address the claims as amended.
Applicants cite case law and contend in essence that as presently amended, the entire scope of the claims is adequately represented by the species disclosed in the specification. Applicants submit that the specification also describes SEQ ID NOs: 12 and 20 species of the genus and details possession of 22BF, BurkF, PaF, YerF, CT053-CopB, CT053-CopB2, CT668-CopB, or CT668-CopB2 fusion proteins each with LTA-1. Applicants refer to MPEP 2164.04 and submit that the Patent Office must accept the objective truth of statements made in the specification.. .[or provide].. . evidence or convincing argument why those of skill in the art would doubt the statements.” Applicants allege that the Office has provided no such evidence of the existence of any member of the claimed genus that would not be represented by the species described in the specification nor any argument that would objectively establish this fact. Applicants further allege that the Office has simply made conclusory assertions without any supporting legal basis or evidence.
Applicants’ arguments have been carefully considered, but are not persuasive.
Applicants are referred to the written description rejection set forth below in this Office Action to address the claims as amended. Applicants’ arguments still relevant are addressed therein. Contrary to Applicants’ allegation, the Office did not simply make conclusory assertions, instead established the lack of structure-function correlation for the divergent species within the claimed variant genus, the functional unpredictability issue, and the full scope of the claimed invention using the teachings of multiple references from the art including Skolnik et al., Greenspan et al., and Rudinger J, which Applicants have failed to address.
8) The rejection of claims 1-5, 7 and 8 set forth in paragraph 12 of the Office Action mailed 12/19/24 on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1-5 of the US patent 11,439,700 B2 (of record) is withdrawn in light of Applicants’ claim amendments.
Applicants state that they have amended claim 1 to incorporate the features of claim 6 ‘which was not subject to this rejection’.
However, it must be noted that the previous version of claim 6 which was not subject to this rejection was limited to Pseudomonas spp exolysin (ExlA). Contrary to Applicants’ statement, claim 1 has not been amended currently to incorporate the previous limitation ‘Pseudomonas spp exolysin (ExlA)’ from claim 6 in to the independent claim 1. Applicants are referred to the new rejection set forth in this Office Action to address the claims as amended.
9) The provisional rejection of claims 1, 2, 7 and 8 set forth in paragraph 13 of the Office Action mailed 12/19/24 on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1, 2, 4-6 and 13-15 of the U.S application 17931356 is withdrawn since this application is no more co-pending.
10) The provisional rejection of claims 1, 2, 7 and 8 set forth in paragraph 14 of the Office Action mailed 12/19/24 on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 12, 11, 13, 14, 1-10, 15 and 16 of the co-pending application 18543534 withdrawn in light of Applicants’ claim amendments.
Applicants state that they have amended claim 1 to incorporate the features of claim 6 “which was not subject to this rejection”.
However, it must be noted that the previous version of claim 6 which was not subject to this rejection was limited to Pseudomonas spp exolysin (ExlA). Contrary to Applicants’ statement, claim 1 has not been amended currently to incorporate the previous limitation ‘Pseudomonas spp exolysin (ExlA)’ from claim 6 in to the independent claim 1. Applicants are referred to the new rejection set forth in this Office Action to address the claim as amended.
11) The rejection of claim 6 set forth in paragraph 15 of the Office Action mailed 12/19/24 on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 1-5 of the US patent 11,439,700 B2 (of record) as applied to claim 1 above and further in view of Das et al. (Front. Immunol. 11: Article 583008, pages 1-17, 2020, of record) or WO 2022006748 A1 filed 07/07/2020 (of record) is withdrawn in light of Applicants’ claim amendments. Applicants are referred to the new rejection set forth in this Office Action to address the claim as amended.
12) The rejection of claim 1 set forth in paragraph 17(c), the rejection of claims 4 and 5 set forth in paragraph 17(d), and the rejection of claim 6 set forth in paragraph 17(e) of the Office Action mailed 12/19/24 under 35 U.S.C § 112(b) or pre-AIA , second paragraph, as being indefinite with regard to the limitations “needle tip protein,” “PcrV,” “PopB.” and “ExlA” respectively are withdrawn.
Applicants refer to Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005) and state that claim interpretation is made in light of the specification. Applicants state that understanding is based on what those of skill in the art would understand the terms to mean. Applicants state that each of “needle tip protein,” “PcrV,” “PopB.” and “ExlA” is defined throughout the specification and is well known and understood in the art at the time of filing to refer to particular structures. Applicants state that the term “needle tip protein” is found in 20 peer reviewed papers; “PcrV” is the subject of 151 peer reviewed papers; “PopB” is found in 99 peer reviewed papers; “ExlA” is found in 52 papers.
Applicants’ arguments have been considered. First, no ‘reviewed papers’ have been submitted to the Office wherein one could find the terms “needle tip protein”, “PcrV”, “PopB” and “ExlA” for one to understand whether or not these alleged terms have any relevance to the recited Gram negative bacterial elements and whether or not they fall within each of the claimed genus, structure-wise and scope-wise. Second, based on the description in the as-filed specification, for example, under the section entitled “Protein variants”, each of the identified limitations is interpreted as including or encompassing all structurally highly variable homologs, derivatives, variants, analogs, fragments, and substitutional, insertional and deletional variants having at least 70% homology, i.e., up to 30% non-homology, to each protein sequence.
13) The rejection of claim 3 set forth in paragraph 17(b) of the Office Action mailed 12/19/24 set forth in paragraph 15 of the Office Action mailed 12/19/24 under 35 U.S.C § 112(b) or pre-AIA , second paragraph, as being indefinite is withdrawn in light of Applicants’ claim amendment.
14) The rejection of claim 8 set forth in paragraph 17(f) of the Office Action mailed 12/19/24 set forth in paragraph 15 of the Office Action mailed 12/19/24 under 35 U.S.C § 112(b) or pre-AIA , second paragraph, as being indefinite is withdrawn in light of Applicants’ claim amendment.
15) The rejection of claims 1-5, 7 and 8 set forth in paragraph 19 of the Office Action mailed 12/19/24 under 35 U.S.C § 102(a)(1) as being anticipated by WO 2019/217243 A1 (‘243, of record) is withdrawn in light of Applicants’ amendments to the base claim.
Applicants state that they have amended claim 1 to incorporate the features of claim 6 ‘which was not subject to this rejection’.
However, it must be noted that the previous version of claim 6 which was not subject to this rejection was limited to Pseudomonas spp exolysin (ExlA). Contrary to Applicants’ statement, claim 1 has not been amended to incorporate the ‘Pseudomonas spp exolysin (ExlA)’ limitation in to the independent claim 1.
16) The rejection of claims 1-5, 7 and 8 set forth in paragraph 20 of the Office Action mailed 12/19/24 under 35 U.S.C § 102(a)(1) as being anticipated by Das et al. (Front. Immunol. 11: Article 583008, pages 1-17, 17 November 2020, of record) is withdrawn in light of Applicants’ amendments to the base claim.
Applicants state that they have amended claim 1 to incorporate the features of claim 6 ‘which was not subject to this rejection’.
However, it must be noted that the previous version of claim 6 which was not subject to this rejection was limited to Pseudomonas spp exolysin (ExlA). Contrary to Applicants’ statement, claim 1 has not been amended to incorporate the ‘Pseudomonas spp exolysin (ExlA)’ limitation in to the independent claim 1.
17) The rejection of claim 6 set forth in paragraph 22 of the Office Action mailed 12/19/24 under 35 U.S.C § 103 as being unpatentable over WO 2019/217243 A1 (‘243, of record) as applied to claim 1 above and further in view of Das et al. (Front. Immunol. 11: Article 583008, pages 1-17, 2020, of record) or WO 2022006748 A1 filed 07/07/2020 (of record) is withdrawn in light of Applicants’ claim amendments including those to the base claim. Applicants’ arguments are moot in light of the withdrawal of the rejection. A new rejection is set forth below to address the claim as amended.
Rejection(s) under 35 U.S.C § 112(a) or (Pre-AIA ) Second Paragraph Maintained
18) The rejection of claim 1 set forth in paragraph 17(c) of the Office Action mailed 12/19/24 set forth in paragraph 15 of the Office Action mailed 12/19/24 under 35 U.S.C § 112(b) or pre-AIA , second paragraph, as being indefinite with regard to the limitation ‘translocator protein’ is maintained. Applicants have not addressed this part of the rejection.
19) The rejection of claims 2-8 set forth in paragraph 17(g) of the Office Action mailed 12/19/24 set forth in paragraph 15 of the Office Action mailed 12/19/24 under 35 U.S.C § 112(b) or pre-AIA , second paragraph, as being indefinite is maintained for the reason(s) set forth therein.
Rejection(s) under 35 U.S.C § 112(a) or (Pre-AIA ) First Paragraph
20) 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 the invention.
21) Claims 1-8 are rejected under 35 U.S.C § 112(a) or 35 U.S.C § 112 (pre-AIA ), first paragraph, as containing 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 written description rejection.
The purpose of the written description requirement is “to ensure that the inventor had possession, as of the filing date of the application relied on, of the specific subject matter later claimed by him.” In re Edwards, 568 F.2d 1349, 1351-52, 196 USPQ 465, 467 (CCPA 1978). The analysis of whether the as-filed specification complies with the written description requirements calls for the Office to compare the scope of the claims with the scope of the description to determine whether Applicants have demonstrated possession of the full scope of the claimed invention at the time of the invention. In the instant application, an analysis of the scope of the claims and of the variant protein genus encompassed therein indicates the following.
Claim 1, as amended, is representative of the claimed invention. It is now drawn to a composition comprising (a) one or more fusion polypeptides comprising a fusion of a needle tip protein or an antigenic fragment thereof and/or a translocator protein or an antigenic fragment thereof from a Type III secretion system (T3SS) of a Gram-negative bacterium, and the elected species of A1 subunit of LTA1 toxin from enterotoxigenic E. coli; and (b) a pore forming toxin. The alternative term ‘or’ in part a) i) of claim 1 permits the claimed one or more fusion polypeptides to comprise (1) fusions of a needle tip protein or an antigenic fragment thereof, or (2) fusions of a translocator protein or an antigenic fragment thereof. While claim 3 identifies the Gram-negative bacterium as the Pseudomonas spp., i.e., the elected species, the Gram-negative bacterium encompassed within the breadth of claims 1, 2 and 4-8 represent a huge genus encompassing infinite number of taxonomically, genetically, and antigenically divergent Gram-negative bacterium species. The elected PcrV and PopB proteins of Pseudomonas spp. and their antigenic fragments are not identified by a specific structure or SEQ ID number(s) in the instant claims. Accordingly, the broadly recited ‘a needle tip protein’ and ‘a translocator protein’ of such Gram-negative bacterium, each represents a humongous genus of needle tip proteins and translocator proteins of unlimited variable structure, size and/or length, and antigenic fragments thereof. Said structurally divergent needle tip protein species and said structurally divergent translocator protein species are not limited to those recited in claims 4 and 5, PcrV and PopB being the elected species, or to SEQ ID NO: 8, 12 or 20, or to native unmodified needle tip proteins and/or translocator proteins of a defined or known structure; instead, they encompass innumerable highly variable mutant species, homolog species, isoform species, derivative species, variant species, analog species, ortholog species, fragment species etc of variable structure and size/length. Said variant genus includes derivatives, mutants, substitutional, insertional and deletional variants comprising one or more, including up to 30 amino acid deletions, insertions or substitutions, and variants having at least 70% homology to a particular sequence. See the definition set forth at the section entitled ‘Protein variants’ in the as-filed specification. The same genus-species analysis applies also to the currently added ‘a pore forming toxin’ that is now an active element of the claimed composition and to ‘ExlA’ since the description in the as-filed specification includes protein variant species, mutant species, and derivative species of a pore forming toxin, for example, SEQ ID NO: 2. See at least page 36 of Applicants’ specification. Said ‘a pore forming toxin’ is also a large genus encompassing structurally divergent bacterial, non-bacterial, prokaryotic, and eukaryotic pore forming toxin species. For example, the latter encompasses at least sticholysin II, equinatoxin II, and actinoporin species from sea anemones. See at least page 1220 of Hinds et al. J. Mol. Biol. 315: 1219-1229, 2002. Actinoporins are known in the art to differ from bacterial pore-forming toxins in several respects. See the full sentence bridging pages 1219 and 1220 of Hinds et al. J. Mol. Biol. 315: 1219-1229, 2002. It was known in the art at the time of the invention that in contrast to bacterial pore-forming pores (PFPs), the mechanism of pore formation by the actinoporin pore-forming species is poorly defined due in part to the scarcity of structural information. See 1st full sentence of the last full paragraph on page 1319 of Mancherio et al. Structure 11: 1319-1328, 2003. This is important because the only pore forming toxin species with its structure disclosed is the full length ExlA of SEQ ID NO: 2 and its C-terminal amino acid sequence of SEQ ID NO: 4. Part (2) on page 59 of the as-filed specification indicates that the ExlA that is produced and used in the instant application is said ExlA C-terminus species. These are important because the The claimed composition comprising the genus of one or more fusion polypeptides comprising a fusion of said protein species and/or their antigenic fragment species of variable structure and length/size and a pore forming toxin genus similarly encompassing structurally variable species is required to have the vaccine function as is evident from claim 8 and the as-filed specification, and is required to treat, inhibit, or prevent a Gram-negative bacterial infection in a subject as is evident from claim 10 and the as-filed specification. Infection by Gram negative bacteria against which the claimed vaccine is required to work very broadly encompasses within its broad scope, innumerable local and topical infections, systemic and non-systemic infections, invasive and non-invasive infections, disseminated and non-disseminated infections including highly fatal meningitis and septicemia by a humongous Gram negative bacterial genus that includes at least Veillonella sp., Flavobacterium species, Porphyromonas gingivalis, Borrelia species, Chlamydia pneumoniae, Chlamydia trachomatis, Chlamydophila psittaci, Citrobacter freundii, Proteus species, Enterobacter sakazakii, Enterococcus faecium, Escherichia coli, Francisella tularensis, Haemophilus ducreyi, non-pylori Helicobacter, Legionella pneumophila, Leptospira interrogans, Mycoplasma pneumoniae, Neisseria meningitidis, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Bacteroides species, Rickettsiae, Coxiella burnetii, Pasteurella multocida, Pasteurella hemolytica, Salmonella typhi, Salmonella paratyphi A, B and C, Salmonella enteritidis, Shigella sonnei, Shigella flexneri, Shigella dysenteriae, Shigella boydii, Treponema pallidum, Vibrio cholerae, Vibrio parahemolyticus, Vibrio vulnificus, Yersinia enterocolitica, Yersinia pestis etc. See section [0019] of Lozano et al. (US 20140206016 A1, of record). However, at the time of invention, Applicants were not in possession of the variable genus of the recited proteins of the fusion and their variable antigen fragments and the full breadth of the fusion polypeptides as well as of the variable pore forming toxin genus and a vaccine comprising the one or more of the fusion polypeptides as claimed.
Sufficient description to show possession of a genus may be achieved by means of disclosure of a representative number of the broadly claimed protein species and their antigenic fragment species of variable structure, defined by structure or amino acid sequences falling within the scope of the broad variant genus, or recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Possession may not be shown by merely describing how to obtain members of the claimed genus or how to identify their common structural features. 35 U.S.C § 112 requires a written description of the claimed invention that allows a person of skill in the art to recognize that the inventor invented what is claimed. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010). To that end, to satisfy the written description requirement, the inventor "must ... convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention." Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563-64 (Fed. Cir. 1991). "One shows that one is in possession of the invention by describing the invention, with all its claimed limitations." Ariad Pharms. v. Eli Lilly, 598 F.3d 1336, 1350 (Fed. Cir. 2010) (When a genus of a biomolecule is claimed in a patent, adequate written description of representative species of the biomolecules themselves is required in the specification.) Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (internal citation omitted). In University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), the court held that, when a genus of peptides is claimed, the written description must sufficiently define the genus to allow one skilled in the art to "visualize or recognize the identity of the members of the genus," for example, by describing a representative number of species or a description of "structural features commonly possessed by members of the genus that distinguish them from others." University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997). An adequate written description must contain enough information about the actual makeup of the claimed products - "a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials," which may be present in "functional" terminology "when the art has established a correlation between structure and function." Ariad, 598 F.3d at 1350. "The 'written description' requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor's obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed." Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005):
The descriptive text needed to meet these requirements varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence. The law must be applied to each invention that enters the patent process, for each patented advance is novel in relation to the state of the science. Since the law is applied to each invention in view of the state of relevant knowledge, its application will vary with differences in the state of knowledge in the field and differences in the predictability of the science.
Capon, 418 F.3d at 1357. The disclosure necessary to fulfil the written description requirement must be considered in the context that the specification relied upon the existing scientific and technical knowledge of the proteins and antigenic fragments as recited broadly.
The written description requirement can be met by describing the claimed subject matter to a person skilled in the art using sufficiently detailed, relevant identifying characteristics such as functional characteristics and correlating those functional characteristics with a disclosed structure. See Enzo Biochem v. Gen-Probe, 323 F.3d 956, 964, 967, 968 (Fed. Cir. 2002). A review of the instant specification indicates that at the time of the invention, Applicants were in possession of the elected Pseudomonas PcrV-PopB fusion polypeptide species, i.e., SEQ ID NO: 8 and a vaccine comprising the same. Applicants were not in possession of a representative number and variety of structurally divergent fusion polypeptide species within the claimed broad genus comprising the recited needle tip protein and/or the translocator protein or antigenic fragments thereof, or the PcrV protein and/or the PopB protein or their antigenic fragments, wherein their divergent structure is correlated with the requisite vaccine functions, i.e., prophylactic and therapeutic protective effects against any generic Gram negative bacterial infection in a subject. The structure-function correlation is lacking for a sufficient number and variety of the needle tip protein species and the translocator protein species or their antigenic fragment species, and the PcrV protein and the PopB protein species or their antigenic fragment species that are representative of the claimed broad genus. The claimed genus is not limited to native unmodified needle tip proteins and/or translocator proteins of a defined or known structure; instead, the claimed huge genus encompasses innumerable highly variable mutant species, homolog species, isoform species, derivative species, variant species, analog species, ortholog species, fragment species etc of variable structure and size/length. Said variant genus includes derivatives, mutants, substitutional, insertional and deletional variants comprising one or more, including up to 30 amino acid deletions, insertions or substitutions, and variants having at least 70% homology to a particular sequence that are required to have the requisite ‘vaccine’ functions. The divergent structure of a representative number and variety of such variants has not been correlated with the ‘vaccine’ functions. The structure-function correlation is lacking for a sufficient number and variety of the needle tip protein species and the translocator protein species or their antigenic fragment species, and the PcrV protein and the PopB protein variant species or their antigenic fragment species that are representative of the claimed broad genus.
This is important because for inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. A ‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus as in the instant case, one must describe a sufficient variety of species to reflect the variation within the genus. The single fusion polypeptide species of SEQ ID NO: 8 is not representative of the claimed incredibly large genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated”).
The written description inquiry is case- and context-specific. It “depend[s] on the nature of the claimed invention and the knowledge of one skilled in the art at the time an invention is made and a patent application is filed.” Ariad, 560 at 1372. A number of factors guide the inquiry, including “the existing knowledge in the particular field, the extent and content of the prior art, the maturity of the science or technology, and the predictability of the aspect at issue.” Ariad, 560 at 1372 [Emphasis added]. According to MPEP 2163 [Emphasis added]:
The description needed to satisfy the requirements of (pre-AIA ) 35 U.S.C § 112 “varies with the nature and scope of the invention at issue, and with the scientific and technologic knowledge already in existence.” Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084. Patents and printed publications in the art should be relied upon to determine whether an art is mature and what the level of knowledge and skill is in the art.
Evidence required to demonstrate possession of the invention is fact-specific and varies inversely with the maturity and predictability of the technology area. Inventions in “unpredictable” arts are subject to greater scrutiny under the written description requirement, and require a greater showing of possession than more predictable arts. In the instant application, at the time of the invention, Applicants were not in possession of a representative number and variety of the encompassed protein variant species such as those that are up to 70% homologous to generic Gram negative bacterial or to Pseudomonas needle tip protein and translocator protein of a specific structure or SEQ ID number(s) and pore forming toxins, wherein the protein species and their antigenic fragment species and the pore forming toxin species are correlated with the requisite ‘vaccine’ functions and Gram negative bacterial infection-treating, -preventing and -inhibiting functions. This is critically important because the encompassed species that are up to 30% non-homologous to the recited needle tip protein and the translocator protein or to the Pseudomonas PcrV and PopB proteins are permitted to have amino acid substitutions, deletions, insertions and/or other modifications, yet are required to retain the requisite vaccine functions. However, the as-filed disclosure fails to provide adequate description on the precise position(s), the nature and extent of amino acid replacements, deletions, truncations, mutations, or variations that can be made within each of the proteins in order to produce up to 30% non-homologous species thereof and their antigenic fragments having the requisite vaccine function(s), and with regard to whether these variant proteins-containing fusion polypeptide would serve as an effective vaccine against Gram negative bacterial infections. There is no predictability that the various up to 30% non-homologous needle tip protein species and translocator protein species and their antigenic fragment species encompassed within the scope of the claims would have the requisite vaccine functions against any Gram negative bacterial infections. Applicants have not identified which contiguous or discontiguous determinants, or conformational or non-conformational epitopes within the recited proteins and their antigenic fragments are correlated with the requisite vaccine function(s) such that a skilled artisan would have known what modifications, substitutions, or variations could be made in their amino acid sequence species currently encompassed within the scope of the broad genus without losing the requisite vaccine functions. This is important because the art reflects unpredictability as to which amino acids in a specific protein or a polypeptide sequence can be varied without adversely affecting the functional properties of that specific protein or polypeptide sequence. While it is known in the art that variation in one or more amino acids is possible in a given protein or amino acid sequence, the exact position within its amino acid sequence where replacements or variations can be made, with a reasonable expectation of success of retaining the protein’s or polypeptide sequence’s functional competence or integrity, is not certain or predictable. A random replacement affecting the protective epitopic amino acid positions that are critical, for example, to the three-dimensional conformational structure and specific binding property of the protein, would result in a protein that may be non-functional, or not optimally functional, because such positions tolerate no or little modifications. In the instant case, this is important because the purpose of the instantly claimed structurally variable protein species is to use them as an anti-Gram negative bacterial vaccine. With regard to this issue, Skolnick et al. (Trends in Biotechnology, 18: 34-39, 2000, of record) teach that the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based on sequence homology is inaccurate, in part because of the multifunctional nature of proteins. See abstract and ‘Sequence-based approaches to function prediction’ on page 34. Skolnick et al. teach that even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to function of the structurally related protein. See in particular abstract and Box 2. With regard to the structure-function relationship of an encoded amino acid sequence in general, Rudinger J. (In: Peptide Hormones. (Ed) JA Parsons, University Park Press, pages 1-7, 1976, of record) taught that ‘the significance of particular amino acid sequences for different aspects of biological activity cannot be predicted a priori but must be determined from case to case by painstaking experimental study’. See page 6 of Rudinger J. Rudinger J. further taught that ‘it is impossible to attach a unique significance to any residue in a sequence’ and that a ‘given amino acid will not by any means have the same significance in different peptide sequences, or even in different positions of the same sequence. See page 3 of Rudinger J. Furthermore, the art recognizes that defining epitopes is not easy and there is a confusing divergence between the textbook definition of epitope and the definition that is in use in published descriptions of experimental investigations and that epitopes must be empirically determined. See Greenspan et al. Nature Biotechnology 17: 936-937, 1999 (of record). To satisfy the written description provision of 35 U.S.C § 112(a) or pre-AIA , first paragraph, a convincing structure-function relationship must exist between a representative number of the structurally variable protein species, their antigenic fragment species, and their vaccine function(s). Such a structure-function correlation is lacking. Species must be adequately described and must fairly represent the variation within the entire genus. In the instant case, with the structure being unspecified or unidentified in the claims, the needle tip protein genus, the translocator protein genus, and the antigenic fragments thereof, and the ExlA genus encompass numerous variant and fragment species of limitless structure with no predictability of retaining the requisite vaccine functions and Gram negative bacterial infection-treating, -preventing and -inhibiting functions. Applicants have not described the variant genus such that the specification might reasonably convey to a skilled artisan that Applicants had possession of the claimed invention at the time the application was filed.
Note that Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991) states “we hereby reaffirm, that 35 U.S.C § 112 (pre-AIA ), first paragraph, requires a ‘written description of the invention’ which is separate and distinct from the enablement requirement”. In re Ruschig, 379 F.2d 990 (CCPA 1967) states that written description is one of three distinct requirements under 35 U.S.C § 112 (pre-AIA ), first paragraph. MPEP § 2163.02 states: ‘an objective standard for determining compliance with the written description requirement is, does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed’. The courts have decided that the purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed. See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Applicants should note that written description requires more than a mere statement that something is part of the invention and a reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Characterization of a representative number of the species as claimed with their precise structure correlated with the requisite or intended functions is required. With respect to the written description requirement, while ‘examples explicitly covering the full scope of the claim language’ typically will not be required, a sufficient number of representative species must be included ‘to demonstrate that the patentee possesses the full scope of the [claimed] invention’. Lizardtech Inc. v. Earth Resource Mapping, Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724, 1732 (Fed. Cir. 2005). As set forth supra, encompassed within the scope of the huge genus are numerous structural variants and fragments. The as-filed specification does not describe sufficient members of the claimed genus by complete structure along with correlation to the requisite functions. One of skill in the art would not reasonably conclude that the instant disclosure provides a representative number of species to describe the entire genus. The as-filed specification does not contain a written description sufficient to show that he or she had possession of each variant genus and the full scope of the claimed invention at the time the application was filed.
It must be noted that Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005) states:
"When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" [Emphasis added].
MPEP § 2163.02 states: ‘an objective standard for determining compliance with the written description requirement is, does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed’. The courts have decided that the purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed. See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 U.S.C § 112 (pre-AIA ) is severable from its enablement provision. Applicants should note that written description requires more than a mere statement that something is part of the invention and a reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The specific description or guidance, not general description or guidance is needed. A mere idea or unsubstantiated function is insufficient for written description; characterization of a representative number of species in an unpredictable art, with their precise structure correlated with the requisite functions, is required in order to claim the broad genus. Clearly, at the time of the invention Applicants were not in possession of a representative number and variety of the needle tip protein species, the translocator protein species, the pore-forming toxin species, and the ExlA species, which were correlated with the above-identified requisite functions. A convincing structure-function correlation is lacking in the instant application. The specification does not describe the claimed embodiments in sufficient detail to convey to a person skilled in the art that Applicants were in possession of each of the variant genus and the full scope of the claimed invention at the time of filing. The scope of the claims is broader than what is justified by the written description within the as-filed specification. Clearly, Applicants did not describe the invention of the instant claims sufficiently to show that they had possession of the claimed broad method. Instant claims do not meet the provision of 35 U.S.C § 112 (pre-AIA ), first paragraph or 35 U.S.C § 112(a).
Double Patenting Rejection(s)
22) Claims 1-8 are rejected on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 5 and 1-4 of US patent 11,439,700 B2 (of record) in view of Das et al. (Front. Immunol. 11: Article 583008, pages 1-17, 2020, of record) and WO 2022006748 A1 filed 07/07/2020 (‘748, of record).
Although the two claim sets are not identical, they are not patentably distinct from each other. Said claims of the ‘700 patent because are drawn to a vaccine composition comprising a fusion polypeptide comprising a fusion of a PcrV needle tip protein or an antigenic fragment thereof and a PopB translocator protein or an antigenic fragment thereof from Pseudomonas spp., the needle tip protein being 5’ to the translocator protein; and a LTA1 from enterotoxigenic E. coli being 5’ of the fusion.
The disclosure of the ‘700 patent is silent on the vaccine composition comprising the fusion polypeptide therein further comprising a pore forming toxin such as Pseudomonas spp. exolysin A (ExlA).
However, WO ‘748 disclosed expression of the exolysin A (ExlA) of Pseudomonas aeruginosa, a medical effector antigen that elicits at least one immune response in a subject to treat a target disease or condition including cancer. The ExlA is taught as a virulence factor and an anticancer effector. The ExlA elicited anticancer immunity and thereby repressed the tumor growth. See lines 5-6 on page 4; lines 26-32 of page 9; lines 15-16 and 20-22 of page 26; lines 20-22 of page 27; lines 4-10 and 14-15 of page 29; lines 4-6 of page 35; lines 34-35 of page 37; claims 40, 39 and 34; and Figure 4.
Most importantly, in addition to teaching an efficacious L-PaF vaccine based on the novel antigen PaF (the Pa Fusion), which is a fusion polypeptide of the Pseudomonas aeruginosa T3SS needle tip protein, PcrV, and the translocator protein, PopB, and the N-terminally fused A1 subunit of the double-mutant heat-labile enterotoxin, LTA1 to prevent Pseudomonas aeruginosa infections (see Abstract/Summary on page 1; last full paragraph on page 2; 1st full paragraph of page 4; and paragraph bridging the two columns on page 5; Figures 1-4; the paragraph bridging pages 5 and 6; and pages 9-13), Das et al. expressly taught that said fusion polypeptide does not provide protection against T3SS-lacking PA7-like clade Pseudomonas strains that kill cells via exolysin A (ExlA) rather than T3SS and suggested generation of vaccines against this outlier group of strains. See paragraph 2 of column 2 of page 14.
Given the teachings of Das et al. and WO ‘748, it would have been prima facie obvious to one of ordinary in the art before the effective filing date of the claimed invention to include WO ‘748’s medical effector ExlA antigen of Pseudomonas aeruginosa having the advantageous anticancer immunity-inducing and tumor growth-suppressing therapeutic activities to patent ‘700’s vaccine composition comprising the PcrV-PopB and LTA1 fusion polypeptide to produce the instant invention. Given the identified need in the art for a vaccine against the outlier group of T3SS-lacking strains of Pseudomonas aeruginosa strains as indicated by Das et al., and given the teachings in the art of using Pseudomonas aeruginosa ExlA antigen as an anti-cancer medical effector, one of ordinary skill in the art would have been motivated to produce the instant invention for the expected benefit of producing advantageously a LTA1-PcrV-PopB fusion polypeptide-containing vaccine composition that also comprises Pseudomonas aeruginosa ExlA medical effector antigen having not only the demonstrated anti-cancer effect and tumor growth suppressing effect, but which also advantageously covers the art-known outlier T3SS-lacking strains of Pseudomonas aeruginosa in addition to covering T3SS-producing strains of Pseudomonas aeruginosa.
23) Claims 1-8 are rejected on the ground of non-statutory obviousness-type double patenting as being unpatentable over claims 5, 1-4, 8 and 9 of US patent 12331085 in view of Das et al. (Front. Immunol. 11: Article 583008, pages 1-17, 2020, of record) and WO 2022006748 A1 filed 07/07/2020 (‘748, of record).
Although the two claim sets are not identical, they are not patentably distinct from each other. Said claims of the ‘085 patent are drawn to a vaccine composition comprising a fusion polypeptide comprising SEQ ID NO: 36 (PaF) and a dmLT or SEQ ID NO: 38 (LTA1-PaF) comprising therein PcrV protein of Pseudomonas spp. and PopB protein of Pseudomonas spp.
The disclosure of the ‘085 patent is silent on the vaccine composition comprising the fusion polypeptide therein further comprising a pore forming toxin such as Pseudomonas spp. exolysin A (ExlA).
However, WO ‘748 disclosed expression of the exolysin A (ExlA) of Pseudomonas aeruginosa, a medical effector antigen that elicits at least one immune response in a subject to treat a target disease or condition including cancer. The ExlA is taught as a virulence factor and an anticancer effector. The ExlA elicited anticancer immunity and thereby repressed the tumor growth. See lines 5-6 on page 4; lines 26-32 of page 9; lines 15-16 and 20-22 of page 26; lines 20-22 of page 27; lines 4-10 and 14-15 of page 29; lines 4-6 of page 35; lines 34-35 of page 37; claims 40, 39 and 34; and Figure 4.
Most importantly, in addition to teaching an efficacious L-PaF vaccine based on the novel antigen PaF (the Pa Fusion), which is a fusion polypeptide of the Pseudomonas aeruginosa T3SS needle tip protein, PcrV, and the translocator protein, PopB, and the N-terminally fused A1 subunit of the double-mutant heat-labile enterotoxin, LTA1 to prevent Pseudomonas aeruginosa infections (see Abstract/Summary on page 1; last full paragraph on page 2; 1st full paragraph of page 4; and paragraph bridging the two columns on page 5; Figures 1-4; the paragraph bridging pages 5 and 6; and pages 9-13), Das et al. expressly taught that said fusion polypeptide does not provide protection against T3SS-lacking PA7-like clade Pseudomonas strains that kill cells via exolysin A (ExlA) rather than T3SS and suggested generation of vaccines against this outlier group of strains. See paragraph 2 of column 2 of page 14.
Given the teachings of Das et al. and WO ‘748, it would have been prima facie obvious to one of ordinary in the art before the effective filing date of the claimed invention to include WO ‘748’s medical effector ExlA antigen of Pseudomonas aeruginosa having the advantageous anticancer immunity-inducing and tumor growth-suppressing therapeutic activities to patent ‘085’s vaccine composition comprising the LTA1-PaF fusion polypeptide to produce the instant invention. Given the identified need in the art for a vaccine against the outlier group of T3SS-lacking strains of Pseudomonas aeruginosa strains as indicated by Das et al., and given the teachings in the art of using Pseudomonas aeruginosa ExlA antigen as an anti-cancer medical effector, one of ordinary skill in the art would have been motivated to produce the instant invention for the expected benefit of producing advantageously a LTA1-PaF fusion polypeptide-containing vaccine that also comprises Pseudomonas aeruginosa ExlA medical effector antigen having not only the demonstrated anti-cancer effect and tumor growth suppressing effect, but which also advantageously covers the art-known outlier T3SS-lacking strains of Pseudomonas aeruginosa in addition to covering T3SS-producing strains of Pseudomonas aeruginosa.
Rejection(s) under 35 U.S.C § 112(b) or (Pre-AIA ), Second Paragraph
24) 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.
25) Claim 2 is rejected under 35 U.S.C § 112(b) or pre-AIA , second paragraph, as being indefinite, for failing to particularly point out and distinctly claim the subject matter which inventor or a joint inventor, or for the pre-AIA the Applicants regard as the invention.
The dependent claim 2 is ambiguous and indefinite and has an antecedence issue with regard to the limitation ”the fusion polypeptide”. Claim 2 depends from claim 1, which as amended currently includes the limitation ‘fusion polypeptides’ [Emphasis added].
Rejection(s) under 35 U.S.C § 103
26) 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 of this title, 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 claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 148 USPQ 459, that are applied for establishing a background for determining obviousness under 35 U.S.C § 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or unobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicants are advised of the obligation under 37 C.F.R 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned at the time a later invention was effectively filed in order for the examiner to consider the applicability of 35 U.S.C § 102(b)(2)(C) for any potential 35 U.S.C § 102(a)(2) prior art against the later invention.
27) Claims 1-8 are rejected under 35 U.S.C § 103 as being unpatentable over WO 2019/217243 A1 (‘243, of record) in view of Das et al. (Front. Immunol. 11: Article 583008, pages 1-17, 2020, of record) and WO 2022006748 A1 filed 07/07/2020 (of record).
WO ‘243 taught a fusion polypeptide comprising a fusion of the PcrV needle tip protein or an antigenic fragment thereof and/or the PopB translocator protein or an antigenic fragment thereof from a Type III secretion system (T3SS) of a Gram negative bacterium and the A1 subunit of the labile toxin LTA1 of enterotoxigenic E. coli or cholera toxin. A composition or a vaccine comprising one or more of the fusion polypeptides is taught. The fusion polypeptide is arranged so that the needle tip protein 5’ of the translocator protein. The Gram negative bacteria are Pseudomonas spp. The LTA1 is 5’ of the needle tip protein and/or the translocator fusion. See Abstract; claims 1-5, 9 and 11-15; and pages 2-3 and 11-12 .
The disclosure of WO ‘243 is set forth supra, which is silent on the composition or vaccine comprising a pore forming toxin such as Pseudomonas spp. exolysin A (ExlA).
However, WO ‘748 disclosed expression of the exolysin A (ExlA) of Pseudomonas aeruginosa, a medical effector antigen that elicits at least one immune response in a subject to treat a target disease or condition including cancer. The ExlA is taught as a virulence factor and an anticancer effector. The ExlA elicited anticancer immunity and thereby repressed the tumor growth. See lines 5-6 on page 4; lines 26-32 of page 9; lines 15-16 and 20-22 of page 26; lines 20-22 of page 27; lines 4-10 and 14-15 of page 29; lines 4-6 of page 35; lines 34-35 of page 37; claims 40, 39 and 34; and Figure 4.
Most importantly, in addition to teaching an efficacious L-PaF vaccine based on the novel antigen PaF (the Pa Fusion), which is a fusion polypeptide of the Pseudomonas aeruginosa T3SS needle tip protein, PcrV, and the translocator protein, PopB, and the N-terminally fused A1 subunit of the double-mutant heat-labile enterotoxin, LTA1 to prevent Pseudomonas aeruginosa infections (see Abstract/Summary on page 1; last full paragraph on page 2; 1st full paragraph of page 4; and paragraph bridging the two columns on page 5; Figures 1-4; the paragraph bridging pages 5 and 6; and pages 9-13), Das et al. expressly taught that said fusion polypeptide does not provide protection against T3SS-lacking PA7-like clade Pseudomonas strains that kill cells via exolysin A (ExlA) rather than T3SS and suggested generation of vaccines against this outlier group of strains. See paragraph 2 of column 2 of page 14.
Given the teachings of Das et al. and WO ‘748, it would have been prima facie obvious to one of ordinary in the art before the effective filing date of the claimed invention to include WO ‘748’s medical effector ExlA antigen of Pseudomonas aeruginosa having the advantageous anticancer immunity-inducing and tumor growth-suppressing therapeutic activities to WO ‘243’s vaccine composition comprising the PcrV-PopB and LTA1 fusion polypeptide to produce the instant invention. Given the identified need in the art for a vaccine against the outlier group of T3SS-lacking strains of Pseudomonas aeruginosa strains as indicated by Das et al., and given the teachings in the art of using Pseudomonas aeruginosa ExlA antigen as an anti-cancer medical effector, one of ordinary skill in the art would have been motivated to produce the instant invention for the expected benefit of producing advantageously a PcrV-PopB and LTA1-containing composition or vaccine that also comprises Pseudomonas aeruginosa ExlA medical effector antigen having not only the demonstrated anti-cancer effect and tumor growth suppressing effect, but which also advantageously covers the art-known outlier T3SS-lacking strains of Pseudomonas aeruginosa in addition to covering T3SS-producing strains of Pseudomonas aeruginosa.
Claims 1-8 are prima facie obvious over the prior art of record.
28) Claims 1-8 are rejected under 35 U.S.C § 103 as being unpatentable over Das et al. (Front. Immunol. 11: Article 583008, pages 1-17, 2020, of record) and WO 2022006748 A1 filed 07/07/2020 (of record) (‘748).
Das et al. taught a vaccine composition based on the novel antigen PaF (the Pa Fusion), which is a fusion of the Pseudomonas aeruginosa T3SS needle tip protein, PcrV, and the translocator protein, PopB, and the N-terminally fused A1 subunit of the double-mutant heat-labile enterotoxin. Said fusion was designated L-PaF or LTA1-PcrV-PopB, which was efficacious and protective. The prior art vaccine composition comprised PBS and in one embodiment was admixed with dmLT adjuvant. Said novel fusion vaccine was administered intranasally, which expedited the clearance of P. aeruginosa from the lungs of infected mice. See Abstract/Summary on page 1; last full paragraph on page 2; 1st full paragraph of page 4; and paragraph bridging the two columns on page 5; Figures 1-4; the paragraph bridging pages 5 and 6; and pages 9-13.
The teachings of Das et al. are set forth supra, which are silent on their vaccine comprising a pore forming toxin such as Pseudomonas spp. exolysin A (ExlA).
However, WO (‘748) disclosed expression of the exolysin A (ExlA) of Pseudomonas aeruginosa, a medical effector antigen that elicits at least one immune response in a subject to treat a target disease or condition including cancer. The ExlA is taught as a virulence factor and an anticancer effector. The ExlA elicited anticancer immunity and thereby repressed the tumor growth. See lines 5-6 on page 4; lines 26-32 of page 9; lines 15-16 and 20-22 of page 26; lines 20-22 of page 27; lines 4-10 and 14-15 of page 29; lines 4-6 of page 35; lines 34-35 of page 37; claims 40, 39 and 34; and Figure 4.
Most importantly, in addition to teaching an efficacious L-PaF vaccine based on the novel antigen PaF (the Pa Fusion), which is a fusion polypeptide of the Pseudomonas aeruginosa T3SS needle tip protein, PcrV, and the translocator protein, PopB, and the N-terminally fused A1 subunit of the double-mutant heat-labile enterotoxin, LTA1 to prevent Pseudomonas aeruginosa infections (see Abstract/Summary on page 1; last full paragraph on page 2; 1st full paragraph of page 4; and paragraph bridging the two columns on page 5; Figures 1-4; the paragraph bridging pages 5 and 6; and pages 9-13), Das et al. expressly taught that said fusion polypeptide does not provide protection against T3SS-lacking PA7-like clade Pseudomonas strains that kill cells via exolysin A (ExlA) rather than T3SS and suggested generation of vaccines against this outlier group of strains. See paragraph 2 of column 2 of page 14.
Given the teachings of Das et al. and WO (‘748), it would have been prima facie obvious to one of ordinary in the art before the effective filing date of the claimed invention to include WO ‘748’s medical effector ExlA antigen of Pseudomonas aeruginosa having the advantageous anticancer immunity-inducing and tumor growth-suppressing therapeutic activities to Das et al’s composition to produce the instant invention. Given the identified need in the art for a vaccine against the outlier group of T3SS-lacking strains of Pseudomonas aeruginosa strains as indicated by Das et al., and given the teachings in the art of using Pseudomonas aeruginosa ExlA antigen as an anti-cancer medical effector, one of ordinary skill in the art would have been motivated to produce the instant invention for the expected benefit of producing advantageously a LTA1-PcrV-PopB fusion polypeptide-containing vaccine that also comprises Pseudomonas aeruginosa ExlA medical effector antigen having not only the demonstrated anti-cancer effect and tumor growth suppressing effect, but which also advantageously covers the art-known outlier T3SS-lacking strains of Pseudomonas aeruginosa in addition to covering T3SS-producing strains of Pseudomonas aeruginosa.
Claims 1-8 are prima facie obvious over the prior art of record.
Conclusion
29) No claims are allowed.
30) Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 C.F.R 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 C.F.R 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
31) Any inquiry concerning this communication or earlier communications from the Examiner should be directed to S. Devi, Ph.D., whose telephone number is (571) 272-0854. A message may be left on the Examiner’s voice mail system. The Examiner is on a flexible work schedule, however she can normally be reached Monday to Friday from 7.00 a.m. to 4.00 p.m. (EST). If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's Supervisor, Gary Nickol, can be reached at (571) 272-0835. The fax phone number for the organization where this application or proceeding is assigned (571) 273-8300.
32) Information regarding the status of an application may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center or Private PAIR to authorized users only. Should you have questions about access to Patent Center or the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
/S. DEVI/
S. Devi, Ph.D.Primary Examiner
Art Unit 1645
July, 2025
