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 .
Claims 1-8 are pending and under examination.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement filed 7-26-2024 has been considered. An initialed copy is enclosed.
Specification
Claim Rejections - 35 USC § 112
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.
Claims 1-8 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
The claims do not specify what “S1-S6” represent, while abbreviations are permissible, they must be clearly identified. S1 could be supernatant or step or subpart. Clarification is requested.
As to claim 1 and every claim depending thereon, the claims are confusing in that the claims provide for “bacterial cell”, versus bacterial cell suspension. Thus, which bacterial cell is being referenced is confusing as the antecedent basis is unclear. As to “S3” it is unclear what is being referenced by reaching a standard ? What standard? No such standard is defined within the claims and therefore it unclear what is reached. How is a density in the fermentation tank “monitored”. There is no clear mechanism by which density within the tank is determined without removing a sample. In “S3” what is an isotonic injection ? Clarification is requested. “S5” is confusion because it recites “the bacterial solution” which has antecedent basis in claim “S3”. As to “S5” what does a proportion of the whole bacterial solution after irradiation “is qualified”. What is this step ? What is being done to the irradiated bacterial solution… what examination is being done.. the “when” clause makes no sense because no examination step is presented. As to “S6” the claim recites that the resuspending the bacterial solution in the previous recitation, however the previous recitation provides for a bacterial solution ? There is some step missing here.
As to claim 2, what absorbance parameter.. what wavelength ? Is the “standard” the same or different than the standard in claim 1. The phrase lacks clear antecedent basis in claim 1.
As to claim 5, the claim does have clear antecedent basis and not properly further limit the method of claim 1. This claim must specify the irradiation dose of claim is a basic dose of … the language of this claim does not have proper antecedent basis in claim 1, because claim 1 does not state that a basic inactivation does is.
As to claim 6, the same issues are present in claim “6” as “a manner” has no antecedent basis in claim 5.
As to claim 7, the claim step has no antecedent basis in independent claim 1.
As to claim 8, what is stability testing, the specification merely states that it is “accelerated testing” and provides no steps or conditions under which this is performed.
The claims should be rewritten to place in proper English form, provide clear antecedent basis for all terms and be written with active steps in the present and not past tense.
Claim Rejections - 35 USC § 103
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 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.
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 as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention 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.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), 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 nonobviousness.
Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over CN2014189898B (published 2017 hereinafter ‘898; of record on PTOL-1449) in view of CN112410240A and Blake et al (WO 01/74862 A2; published 10-11-2001).
‘898 teaches the preparation of a Pseudomonas aeruginosa vaccine. The method (1) obtains the bacteria strain for preparing a vaccine, (2) breeding the bacterium by seeding in appropriate media, cultivating, and the bacterium is increase in logarithm for a time; (3) obtaining the culture medium containing the bacterium and matrix components by centrifugation/purified to remove culture medium the purification steps can be washed with various solvents to not cause allergic reactions in the body, the preferred solution is washing with sterile normal saline or PBS.(4) a bacteria are resuspended to a particular number, moved to a non-metallic vessel and the bacterial suspension is irradiated 330-3500 Gy and the modes stops 4-5 minutes to irradiate 20-25 minutes by carrying out “circular irradiation”. Dosage is 8-9Gy/minute and irradiation time is 6.2-7.3 hours (instant claims 1, 5 and 6). The bacteria are purified after irradiation and formulated into a vaccine (see pages 1-2 of the Google Patent translation) by adjustment to a final target bacterial concentration. The irradiation is to make the bacteria lose their proliferative activity and retain their metabolic activity. The loss of proliferative activity means that no colonies are produced after being culture on a suitable medium for 24-48 hours. Typically, the bacteria are used which after irradiation have a metabolic activity of 50-70% compared to non-irradiated control bacterial. The rays used in the radiation irradiation are X-rays, gamma rays or rays produced by the isotope radiation source Co60. The method of ray irradiation is low dose, long time and intermittent irradiation. The vaccine can contain an immune adjuvant and present in subcutaneous, intramuscular, oral or nasal cavity inhalation preparations (page 3 of translation). The culture conditions such as medium, time, temperature and rotation speed can be appropriately adjusted according to specific conditions. The temperature suitable for growth is generally at 35-37oC. The pH range can be acidic or basic where the bacterial will not die, the preferred rotating speed is 220 revolutions/minute, and the preferred culturing time is 16-18 hours. The number of bacteria is measured as required to confirm the progress of the culture. The bacteria can be detected by absorbance OD or turbidity and other methods common to the field. The detection method for determining adequate irradiation is set forth to detect non-proliferative ability and detection of metabolic activity retention. The dose of the vaccine can be adjusted according to the condition of the recipient, and the preferred dose is 107-5x109 bacterial bodies and the amounts can be adjusted (see pages 4-5 of the translation). The ‘898 document differs by not preparing a seed medium comprising the Pseudomonas strain, defining the amount of seed liquid to inoculate into the fermentation tank and the conditions of fermentation. The ‘898 document does not teach the centrifugal force and time of centrifugation to collect the bacterial cells from the fermentation. Finally, the ‘898 document does not define the proportion of bacteria in the irradiated bacterial solution.
CN112410240A (published 2-26-2021; hereinafter ‘240). ‘240 teaches collection of Pseudomonas bacteria by centrifugation for 20 minutes at 5000g (page 5 of 9 of Google patent translation).
Blake et al teach conventional fermentation methods for Bacillus pertussis were a 20 liter-bioreaction containing 11 liters of media with inoculated growing bacterial starter culture. The starter cultures were prepared by inoculating shaker flasks containing medium and incubated until an optical density of >1.0 OD600 (page 9, lines 11-17). Blake et al teach that bacterial cultures were inoculated and maintained between approximately 35-37oC and connected to a biocommand unit that collected data for pH, agitation, dissolved oxygen, temperate and air flow rate. Additional pumps for anti-foam agents, and pH control reagents were added as needed as known to those of ordinary skill in the art. Airflow was adjusted to 4.0 liters per minute, dissolved oxygen was maintained at 40% and pH was maintained at approximately 7.2 (page 9, lines 3-11).
It would have been prima facie obvious to one having skill in the art at the time of filing to modify the fermentation method of ‘898 to charge the fermenter with a seed liquid at 2-10% of the fermentation volume, optimize the conditions for fermentation such as the fermentation temperature, the rotation speed, pH value, aeration rate and dissolved oxygen and fermentation time to arrive at the claimed parameters as well as optimizing the collection of Pseudomonas bacteria according to ‘240 using the centrifugation parameters according to ‘240 because and it routine in the art to charge a large fermenter with a starter inoculum/seed and optimize the fermentation parameters of temperature, pH, rotation speed, aeration rate, dissolved oxygen and fermentation time for Pseudomonas aeruginosa because Blake et al such optimization of industrial processes for bacterial production are routine in the art. It further would have been obvious to determine the bacterial cell content of the irradiated bacterial solution by spectrophotometry or other standard means as the art as combined all teach that spectrophotometry provides for a measure of bacterial number/density. Additionally, “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). As to claim 7 and 8, it is routine in the art to determine the inactivation time and dose for irradiating bacteria and also to determine the metabolic activity and lack of bacterial cell proliferation by conventional incubation procedures as a measure of vaccine stability. As such, the steps are conventional and routine optimization procedures for fermentation of bacteria in an industrial setting, the irradiation of fermented bacteria is known to the art for vaccine production and the confirmation of non-proliferative nature of the irradiated bacteria and the presence of metabolic activity is desired in the production of the vaccine. For the foregoing reasons, the method is prima facie obvious to the skilled artisan at the time the invention was filed.
Citation of Relevant Art
Li et al (Scientific Reports, 6:18823, 2015, pages 1-12) teaches X-ray irradiated vaccine confers protection against pneumonia caused by P. aeruginosa.
Ma et al (Signal Transduction and Targeted Therapy 6:353, 2021) teach that an inactivated whole-cell Pseudomonas aeruginosa vaccine acts through the cGAS-STING pathway.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Patricia Duffy/Primary Examiner, Art Unit 1645
Prosecution Insights