The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-21 are under examination on the merits.
DETALIED ACTION
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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) 1 and 6-19 are rejected under 35 U.S.C. 103 as being unpatentable over Steinmetz et al., “Steinmetz’ (Infection and Immunology, 63(10), 3959-3965, 1995, cited in the IDS). Steinmetz in page 3690, column 1, teaches about purification of B. pseudomallei exopolysaccharide (containing CPS) as following:
mucoid strain NTTC 7431 was grown to confluence on modified Ashdown agar plates (5) for 72 h at 37ºC. Colonies were harvested with 20 ml of 0.01 M phosphate-buffered saline (PBS) (0.01 M sodium phosphate buffer made isotonic with saline; pH 7.4) per plate. The collected mucoid material was pooled and stirred vigorously with a magnetic
stirrer for 1h to separate the mucoid layer from the cells and to obtain a uniform
solution. The solution was then centrifuged for 4h at 20,000 Xg at 48ºC to remove
the whole bacteria. The supernatant was heated for 30 min at 80ºC to kill the
remaining viable bacteria and centrifuged for 30 min at 20,000 Xg at 48ºC. The
supernatant was precipitated by adding cold absolute ethanol to a final concentration of 80% (vol/vol) for 1 to 2h at -20ºC. The precipitate was collected by
centrifugation for 30 min at 3,000 3 g at 48ºC, washed once in 80% ethanol for 30
min, and again centrifuged for 30 min. This washing step was repeated once with
96% ethanol. The precipitate was then dissolved in 0.01 M PBS (containing 10
mM MgCl2 and 1 mM CaCl2), and RNase A (100 mg/ml; Sigma) and DNase I
(100 mg/ml; Sigma) were added and the mixture was incubated for 2.5 h at 37ºC
to remove the contaminating RNA and DNA. After incubation, enzymes were
inactivated and denatured by being heated for 30 min at 80ºC and then subjected
to centrifugation for 30 min at 20,000 3 g at 48C. The supernatant was used for
a second precipitation procedure with 80% ethanol as described above, and after
centrifugation, the precipitate was dissolved in 2 ml of deionized water. This
crude material was then used for affinity chromatography.
Immunoglobulin G1 (IgG1) MAb 3015 was coupled to protein A-Sepharose beads (Pharmacia) by using dimethylpimelimidate as a coupling reagent.
The column was loaded with 1 mg of the crude material per 2.5 ml of wet beads.
For elution of the polysaccharide from the column, 100 mM triethylamine (pH
11.5) was used. Fractions were collected and immediately neutralized with acetic
Acid (which is a weak acid). Each fraction was tested in the ELISA (see above) for the presence of exopolysaccharide by using MAb 3015, and positive fractions were pooled, dialyzed against aqua dest (water) overnight, and finally lyophilized.
The purity of the exopolysaccharide preparation was analyzed by SDS-PAGE
followed by a highly sensitive silver staining procedure for the detection of
proteins (23) and LPS (24). For a more sensitive detection of LPS, a quantitative
Limulus amoebocyte lysate assay was kindly performed by Behringwerke AG,
Marburg, Germany. The A260 was measured for DNA and RNA detection.
Therefore, the teachings of Steinmetz as a whole, which refer to all major steps of instant invention with slight but obvious variations render claims 1, and 6-19 obvious.
Claim(s) 2-5, 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Steinmetz (cited above) further in view Bayliss et al., “Bayliss” (Carbohydr Res , 2017 Nov 27; 452:17–24) further in view of Brett (US2020/0338179, 10/29/20, which will be used from now on, for citing relevant text, see also its corresponding patent US patent No.11,235,046, 2/2022).
As mentioned above, Steinmetz suggests a method for isolating CPS from Burkholderia comprising steps (a)-(h) of this invention. Said reference however, does not mention a method of isolating CPS from B. thailandensis.
Bayliss in its abstract teaches that B. thailandensis strain E555 is closely related to B. pseudomallei and B. mallei, but is non-pathogenic to humans and based on immunological cross-reactivity has previously been shown to express a B. pseudomallei-like CPS. In page 18, of Bayliss, it is stated that Whilst extraction of CPS from a virulent B. thailandensis E555 would be an improvement over current methods, as it does not require such inconvenient and expensive procedures for antigen isolation. the CPS (antigen obtained) itself is very much larger than carbohydrate antigens used in licensed vaccines which utilize oligosaccharides, and is not ideal or optimal for melioidosis glycoconjugate development. Bayliss however, does not teach an E555 mutant that which when being subject to extraction for antigen, results in smaller CPS fragments useful for vaccine preparations.
Brett in Example 2, teaches about the preparation of CPS from B. Thailandensis BT2683 mutant which is derived from B. Thailandensis E555, and isolation of said CPS by phenol extraction method (see [0087], inherently resulting in production of 6-deoxy-hetan CPS which has been used by Brett for the production of conjugate vaccines.
Before the effective filing of this application, it would have been obvious to one of ordinary skill in the art who is interested in preparing melioidosis vaccine, to start with the method of Steinmetz and substitute its B. psuedomallei by the B. thailandensis mutants recommended by Bayliss and more specifically, by the mutant of Brett.
One of ordinary skill in the art is motivated in substituting the Burkholderia cells of Steinmetz with E555 mutants of Bayliss and more specifically that of Brett BT2683, because when it comes to preparing vaccines against Melioidosis, the antigens obtained from E555 mutants of Bayliss and more specifically those from Brett BT2683 are more convenient and safer to prepare while being as potent, rendering this invention obvious.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARYAM MONSHIPOURI whose telephone number is (571)272-0932. The examiner can normally be reached full-flex.
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, Melenie L Gordon can be reached at 571-272-8037. 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.
/MARYAM MONSHIPOURI/Primary Examiner, Art Unit 1651
Prosecution Insights