DETAILED ACTION
Election/Restrictions
Applicant’s election of Group I, claims 1-3, in the reply filed on 7/24/26 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 4-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
In the grandparent application, US Serial No. 17/114,417 (now US Patent No. 11,167,019) election to a platform comprising LcrV proteins with Y.pestis and Y.pseudotuberculosis as the Gram-negative bacteria, e.g., Group I. The currently elected invention mirrors the non-elected invention of Group IV in 17/114,417. A double patenting rejection is not applicable due to the restriction requirement that was made in the parent application examined by Examiner Padma Baskar. Vaccine platforms comprising LcrV proteins are a different composition, e.g., and were allowed in the grandparent application. The instant elected Group also mirrors non-elected Group IV in parent application 17/482,527 (now US Patent No. 12,214,030) so no double patenting rejection is applicable against ‘527 either.
Claim Rejections - 35 USC § 112-2nd paragraph
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 1-3 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.
Claims 1-3 are vague and confusing because the claims are unclear whether this is a recombinant Pseudomonas aeruginosa as the specification indicates. Claim 1 uses the langue “including monophosphoryl lipid A and an amount of PcrV proteins isolated from Gram-negative bacteria” which is vague and confusing because it is unclear if these PcrV proteins are from the P. aeurginosa or other bacteria. The claims do not positively recite that the P.aeruginosa is a recombinant P. aeruginosa expressing the monophosphoryl lipid A and an amount of PcrV proteins. There is no mention of heterologous expression in the claims. Appropriate correction and/or clarification is required.
Claim Rejections - 35 USC § 112- Enablement
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 1-3 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The full breadth of the claims recite a vaccine of a P.aeruginosa bacteria comprising a plurality of non-naturally occurring outer membrane vesicles including PcrV of any origin and monophosphoryl lipid A. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use this invention.
Page 6 recites:
[0016] The invention comprises certain Y. pestis mutant constructions that can produce highly immunogenic self-adjuvanting OMVs. Intramuscular immunization with OMVs from these constructions affords significant protection against three pathogenic Yersinia species, Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis in mice.
The specification teaches that the genetically modified Y. pseudotuberculosis strain (YptbS44, Table 4) can produce high amounts of immunogenic OMVs containing homologous and heterologous protective antigens of Y. pestis, B. anthracis or other pathogens. The present invention encompasses a recombinant Yersinia bacterium capable of adapted an Asd+ plasmid using a balance-lethal system to over-synthesize protective antigens and generate OMVs containing these antigens.
The instant specification has taught a hypervesiculating and Δasd Y. pseudotuberculosis mutant strain, YptbS44 [See Table 1 and Supplementary information (SI)] producing adjuvant monophosphoryl lipid A (MPLA)]. The specification teaches these strains with the plasmid pSMV81 which harbors the N-terminal β-lactamase signal sequence (bla ss) and codon-optimized pcrV-hitA fusion (PH) antigen.
The Asd (Aspartate-semialdehyde dehydrogenase)-based balanced-lethal recombinant Yersinia pseudotuberculosis system tailored with an Asd+ plasmid was used to over-synthesize the heterologous PcrV-HitAT fusion antigen (referred to PH), as well as produce high amounts of OMVs encasing the PH antigen. Intramuscular (i.m.) immunization with the rOMV-PH stimulated robust B and T-cell responses and offered great protection against lethal subcutaneous (s.c.) or intranasal (i.n.) challenge with PA103 strain. See Figs 17A-17C, Example 3 (paragraphs 102 and 103), as well as paragraph (113) of the instant specification. Example 3 teaches that several iron acquisition systems are used by Pseudomonas aeruginosa to obtain iron from mammalian hosts during infection and play an important role in bacterial virulence. The hitA (PA4687), hitB (PA4688), and others in PA are involved in iron transportation and associated with bacterial virulence. A study showed immunization with ferric iron-binding periplasmic protein HitA afforded protection against PA infection in mice. Therefore, immunization with OMVs delivering heterologous PcrV and HitA antigens as a bivalent vaccine might potentiate protective immunity against PA infection.
The recombinant Y.pseudotuberculosis strain Yptb was designed to synthezie and adjuvant form of lipid A (MPLA) and was tailored with the Asd+ plasmid pSMV81 dramatically increased the production of outer membrane vesicles (OMVs) enclosing high amounts of the PcrV-HitAT fusion antigen. The genetically modified Y. pseudotuberculosis strain that can produce high amounts of immunogenic OMVs containing heterologous protective antigens of P. aeruginosa (PcrV and HitA). The specification has not taught any other Gram-negative bacteria producing a protective vaccine against lethal challenge with P. aeurginosa. Claims 1-3 recite any PcrV proteins from any origin and do not include a plasmid, nor does the specification provide any working examples for this vaccine. Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: “Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.”
It would take undue experimentation for one of skill in the art to invent another plasmid and adapt a different Gram-negative bacterium, e.g., other than Yersisinia, with the outcome being a protective vaccine with PcrV protein.
Status of claims
No claims are presently allowed. The claims are free of the prior art. The closest prior art of record is Feron et al US 20190091319 A1 3/28/19.
Feron et al discloses a conjugate comprising an antigen (for example a saccharide antigen) covalently linked to a Pseudomonas aeruginosa PcrV carrier protein comprising an amino acid sequence which is at least 80% identical to the sequence of SEQ ID NO:1-4, wherein the antigen is linked (either directly or through a linker) to an amino acid residue of the P. aeruginosa PcrV carrier protein. The invention also discloses Pseudomonas aeruginosa PcrV proteins that contain glycosylation site consensus sequences.
[0008] According to a further aspect of the invention, there is provided an immunogenic composition comprising the conjugate or the PcrV proteins of the invention and a pharmaceutically acceptable excipient.
[0099] Specific examples of adjuvants include, but are not limited to, aluminum salts (alum) (such as aluminum hydroxide, aluminum phosphate, and aluminum sulfate), 3 De-O-acylated monophosphoryl lipid A (MPL) (see United Kingdom Patent GB2220211). In some embodiments, the adjuvant is Freund's adjuvant (complete or incomplete). Other adjuvants are oil in water emulsions (such as squalene or peanut oil), optionally in combination with immune stimulants, such as monophosphoryl lipid A.
However, Feron et al do not teach a platform wherein the recombinant bacteria used to express PcrV and carrier proteins forms OMVs which include monophosphoryl A and the PcrV enclosed. The prior art does not teach or suggest this platform.
Correspondence regarding this application should be directed to Group Art Unit 1645. Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center located in Remsen. The faxing of such papers must conform with the notice published in the Official Gazette, 1096 OG 30 (November 15,1989). The Group 1645 Fax number is 571-273-8300 which is able to receive transmissions 24 hours/day, 7 days/week.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer E. Graser whose telephone number is (571) 272-0858. The examiner can normally be reached on Monday-Friday from 8:00 AM-4 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Thomas Visone, can be reached on (571) 270-0684.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-0500.
/JENNIFER E GRASER/ Primary Examiner, Art Unit 1645 9/9/26
