DETAILED ACTION
Acknowledgment and entry of the Amendment submitted on 4/8/26 is made. Claims 1, 10, 12, 17, 21, 24-35, 40, 42 and 43 are currently pending.
Claims 1, 10, 12, 17, 40 and 42 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. These withdrawn non-elected claims are drawn to a product, while the elected and examined claims are drawn to a method/process. The non-elected claims have been currently amended to depend from the elected methods of producing an inactivated A. baumannii. However, “[t]he patentability of a product does not depend upon its method of production. If the product in [a] product-by-process claim is the same as or obvious from a product of the prior art, [then] the claim is unpatentable even though the prior [art] product was made by a different process.” In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted). New claim 42, drawn to a vaccine, has also been added. Applicants elected a method, not a product. This is the opposite of what is eligible for rejoinder. See MPEP § 804.01.
Claim 21, 24-34 and 43 are currently under examination.
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 21, 24-34 and 43 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 21 is vague and indefinite for use of the phrase “culturing A. baumannii to provide a culture comprising a plurality of A. baumannii” because it makes it unclear if some of the culture is not grown in the same culture batch/conditions or not all A. baumannii. The phrase is ambiguous and/or redundant. It is suggested it be amended to “culturing A. baumannii.” The same applies to the use of “plurality in the second paragraph of the claim. Appropriate clarification and/or correction is required.
Claim 21 is also vague and indefinite for the use of the phrase “using planktonic growth conditions and/or using biofilm growth conditions” because these growth conditions are unclear. These conditions are critical to the method yet there is no standard “biofilm growth condition” or “planktonic growth condition” and these can vary in the art. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
Claim 21 is vague and indefinite due to ‘ionizing radiation’ and/or “ultraviolet radiation in an amount sufficient to inactivate the plurality of A. baumanni.” Again, does use of the term plurality mean some of the culture is not inactivated, just the plurality, e.g., majority? Additionally, it is unclear what amount of ionizing radiation and/or ultraviolet radiation is “sufficient.” While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
Claims 24-28, 33 and 34 also are vague and indefinite for the use of the plurality of A. baumannii” because it makes it unclear if this only applies to some of the A. baumannii, e.g., a plurality/majority vs just A. baumanni (e.g., all of the A. baumanii). The phrase is ambiguous and/or redundant. Appropriate clarification and/or correction is required.
Claim 27 is vague and indefinite due to the broad use of the term “buffer” in a culture growth media. This is an ingredient that is critical to the method and “buffer” allows for any type, pH, ingredients, etc. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
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.
Claim(s) 21-26, 33 and 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over McConnell et al (US 2017/0065700; as provided by Applicants) in view of Gentile et al (Pathogens, vol. 3, no. 3, 18 August 2014 (2014-08-18), pages 704-719; provided by Applicants), Khadke (2019; Biotech & Bioprocess Engineering, 24(2): 359-365, Chapter 3.1; provided by Applicants) and Nairn et al (Cell Host & Microbe, vol. 19, no. 6, June 2016; pages 826-836; provided by Applicants).
The instant claims describe a generic method of irradiating A. baumanni whole cells to attenuate them. Independent Claim 21 allows for a method of exposing A. baumannii bacteria to either ionizing radiation and ultraviolet radiation; exposing solely to ionizing radiation; or exposing solely to ultraviolet radiation. The process is not limited to any particular dose and cover products with an entire gamut of vague random mutations at random positions. The prior art is applied accordingly. The new amended term in independent claim 21, e.g., using planktonic and/or biofilm growth conditions, is not limiting as the claims do not define these conditions and they vary greatly in the prior art. Since no particular growth conditions are specified (medium, oxygen, temperature, etc.) no particular expression profile follows. These seem to be routine growth-conditions for A. baumanni, as shown Nairn et al (planktonic and zinc starvation), Khadke (growth in TSB (tryptic soy broth) under planktonic conditions), and Gentile (describes growth in M9 medium under biofilm conditions for A. baumannii), and thus obvious way of providing a source-material for irradiation. Also, no particular effect is attributed to these growth-conditions in the present specification, neither in terms of vaccine-efficacy nor in terms of degree of inactivation. Since the claims provide no actual description of these conditions, they are obvious over what is taught as “routine” by the prior art.
McConnell discloses A. baumannii immunogen (para [0055]; “In another preferred embodiment of the invention, the cell or strain of the invention is preferably an A. baumannii cell, particularly an attenuated A. baumannii cell.” Paragraph [0051] recites: “It is understood that “inactivated cell" in the present invention is a cell that does not have the ability to replicate but that conserves its immunogenic capacity”), wherein the immunogen is obtained and/or derived from irradiation-inactivated A. baumannii bacteria and/or wherein the immunogen is irradiation-inactivated (para [0051]; The inactivation of the cells of the invention can be performed using diverse methods known in the state of the art for example, although not limited to, ultraviolet light, ionizing radiation"). McConnell further discloses that the A. baumannii immunogen is obtained and/or derived from irradiation-inactivated A. baumannii (para [0051]) grown under conditions such that one or more different bacterial immunogens that stimulate protective immunity are present (para [0051)). McConnell further discloses that the immunogen has been inactivated using ionizing radiation (para [0051]; “ionizing radiation’). McConnell teaches immunogenic composition comprising an attenuated strain of A. baumannii (para [0055]; “preferably an A. baumannii cell, particularly an attenuated A. baumannii cell"); expressing an antigenic epitope-containing bacterial protein (para (0051); "It is understood that “inactivated cell" in the present invention is a cell that does not have the ability to replicate but that conserves its immunogenic capacity"; para [0042]; "By eliminating the LPS component according to the method as detailed in aspect F above, we focus the antibody raising to antibodies against less variable epitopes of the bacterial surface, not related to the LPS component. These epitopes are conserved among A. baumannii strains or individual isolates belonging to all A. baumannii international clones used in A. baumannii classification") wherein bacterial infectivity of the A. baumannii has been decreased or abolished (para [0051]) by ionizing radiation and/or UV radiation (para [0051)).
With respect to instant claim 26, in that the UV is applied for 5 minutes at 3 mW/cm3. No material of the vessel is defined, no volume or cell-number of the bacteria-culture is defined. Hence, a particular dose-per-cell does not follow. A particular DNA-damage load per cell then also does not follow. In absence of a particular technical effect this amounts to routine process optimization of one of multiple interplaying parameters. Additionally, no benefits of combining ionizing and UV radiation are ever discussed in the specification either. Indeed, since intensity/dose of radiation is not defined, no particular damage patterns (number/distribution of DNA-damages) is credible over the whole scope. Adding e.g. insignificant amounts of ionizing radiation is then not inventive. Since McConnell recites both UV radiation and ionizing radiation, it would have been obvious to combine in any manner or solely use one or the other. With respect to instant claim 34, the use of oxygen-free gases such as nitrogen or argon to maintain anoxic conditions in A. baumannii culture systems was widely known to those of ordinary skill in the prior art at the time the invention was made and inert gases such as these are often used to displace oxygen from the headspace above a culture or solution. With respect to new claim 43, it describes a property that is inherent to the A. baumannii inactivated in the cited prior art references.
Claim(s) 27-32 is/are rejected under 35 U.S.C. 103 as being unpatentable over McConnell et al (US 2017/0065700; as provided by Applicants) in view of Daley et a (US 2016/222343; provided by Applicants).
The teachings of McConnell are set forth above. Although McConnell discloses the antigenic epitope- containing bacterial protein (para [0051], [0042]), McConnell does not particularly disclose a culture method which includes exposing the A. baumannii or cultured A. baumanii to a divalent cation peptide and a buffer (instant claims 27-31).
However, Daly discloses the antigenic epitope containing bacterial protein is protected from damage using a chemical complex comprising a manganous ion (Mn2+), a peptide, and a buffer (para (0004); “The invention provides methods of producing vaccines directed against microorganisms, with the methods comprising culturing, harvesting and/or suspending the microorganism in the presence of a radiation-protective composition and irradiating the microorganism with a dose of radiation sufficient to render the microorganism replication-deficient. The radiation-protective compositions used in the methods of the present invention comprise at least one decapeptide in a mixture of manganese-phosphate or manganese-bicarbonate buffer. The invention also provides methods of rendering a bacterium in culture resistant to ionizing radiation (IR), with these methods comprising culturing the bacteria in the presence of a radiation- protective composition"). SEQ ID NO: 1 of Daly is: Asp Glu His Gly Thr Ala Val Met Leu Lys, e.g., the same as SEQ ID NO: 1 of claim 30. One of ordinary skill in the art would have known how to use and include the protective composition described by Daly as a means of protecting the antigenic epitope- containing bacterial protein of McConnell from radiation damage during preparation, without undue difficulty. Consequently, it would have been obvious for one of ordinary skill in the art to combine an antigenic epitope- containing bacterial protein, as disclosed by McConnell, with the antigenic epitope containing bacterial protein is protected from damage using a chemical complex comprising a manganous ion (Mn2+), a peptide, and a buffer, as disclosed by Daly, because it would have prevented the antigenic epitope from being damaged during the irradiation step of the preparation. Instant claim 32 further specifies (i) 0.5-10 mM of MnCl2, (ii) 0.5 - 10 mM of the still vague peptide and (iii) 5-500 mM of phosphate. Due to vagueness, the effect of (ii) is still not apparent, this addition thus still deemed arbitrary. MnCl2 in this range seems to be one among a list of routine supplements for A. baumanni media (see e.g. in light of Gentile and Nairn). Since the Mn, phosphate, decapeptide are supposed to protect the protein-epitopes form damage it would have been obvious that they are contacted with the whole cell during irradiation. One of ordinary skill in the art would have recognized that an irradiation-inactivated bacterial vaccine is generally considered safer than an unattenuated vaccine, and therefore would have used the methods set forth above to generate an irradiation-inactivated A. baumannii immunogen. Facing the technical problem of providing an alternative method of producing an attenuated A. baumanni whole cell vaccine, the skilled person would have had a reasonable expectation of success that applying routine culturing + routine irradiation would ultimately lead to an attenuated A. baumanni strain.
Status of claims:
No claims are presently allowed.
The concept of using irradiation (ultraviolet and/or ionizing radiation) to damage DNA, specifically gene involved in virulence/growth-rate, and thereby reduce DNA-damage has been done for countless bacteria, and then it seems obvious that the same should also be feasible for A. baumanni. All organisms and thus all bacteria have some growth-critical genes, after all.
Pertinent art not presently relied upon:
Dollery et al (Vaccines. January 2021. 9(2): ; provided by Applicants- published after Applicants effective priority date of 12/22/20)
Spellberg et al (US 2012/301474; provided by Applicants) teaches A.baumanii protein vaccines. The only mentioned feature in the product by process claim 40 does not limit the nature/structure of the ultimately isolated immunogen. A known product/protein is not rendered novel merely by being produced by a new method.
Nitzan et al (Current Microbio. June 2001. 42(6): 408-414) discloses photo-inactivation of A. baumannii.
Seo, H. (Clin. Exper. Vaccine Research. July 2015. 4(2): 145-158; provided by Applicants) is a review article that irradiation for vaccine development is broadly applicable to a large and varied host of different pathogens/cells/viruses.
Dubensky et al (Current Opinion in Biotech. December 2012. 23(6): 917-923; provided by Applicants) and Pace et al (Vaccine. October 1998. 16(16): 1563-1574; provided by Applicants) are review articles which teach using gamma-irradiation (Dubensky) and UV-inactivation (Pace) to obtain attenuated bacteria is common knowledge in the art.
Kadke 2019; XPO36786047 discloses A. baumannii growth in TSB under planktonic conditions.
Ainsworth et al (2017; Vaccine. 35(26): 3387-3394; provided by Applicants). discloses UV-inactivated A. baumanni as such (chapter 2.4 and 2.5; and abstract). This is used as analyte. The context as a whole is vaccination with live attenuated strains (see title). Inactivated whole cells of A. baumanni as vaccine candidates seem to be state of the art (page 3388, left column, lines 6-19). It does not specify how long UV was applied.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 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.
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/JENNIFER E GRASER/Primary Examiner, Art Unit 1645 6/1/26
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