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 1-10 are pending in this application are were examined on their merits.
Specification
The disclosure is objected to because of the following informalities: in ¶ 0004, "Celsius degree" should read "degrees Celsius".
Appropriate correction is required.
Claim Objections
Claim 5 objected to because of the following informalities: "Celsius degree" should read "degrees Celsius". Appropriate correction is required.
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.
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.
Claim 3 is 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.
Regarding claim 3: claim 3 further defines the tetravalent dengue inactivated vaccine by reciting the “coating quantities” of DENV-1 – 4 inactivated antigens. As the coating quantities do not refer to the tetravalent dengue inactivated vaccine the wording renders the claim indefinite because it is unclear how the antigens (a liquid) are immobilized as such to be quantified and in a well.
For purposes of compact prosecution and applying prior art, claim 3 was interpreted herein to be antigen immobilized on a plate with a concentration of 1.0 -1.5 µg/well.
It is noted any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office 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.
The factual inquiries 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, 2, and 4-10 are rejected under 35 U.S.C. 103 as being unpatentable over Thomas et al. (WO 2016/145149, hereinafter "Thomas"), and further in view of Hou et al. (Front. Immunol. 2022 Feb 24 13:840104, hereinafter "Hou") and Kirkpatrick et al. (The Journal of Infectious Diseases, Volume 212, Issue 5, 1 September 2015, Pages 702-710, hereinafter "Kirkpatrick").
Regarding claim 1, Thomas teaches a tetravalent dengue vaccine, comprising four serotypes of inactivated antigens; wherein the four serotypes of inactivated antigens comprise a dengue virus serotype 1 (DENV-1) inactivated antigen, a DENV-2 inactivated antigen, a DENV-3 inactivated antigen, and a DENV-4 inactivated antigen (Claim 3 “[t]he immunogenic composition of claim 1, wherein the one or more inactivated dengue viruses consist of an inactivated DENV-1, and inactivated DENV-2, and inactivated DENV-3, and an inactivated DENV-4).
The reference does not teach that the volume ratio of DENV-1 inactivated antigen: DENV-2 inactivated antigen: DENV-3 inactivated antigen: DENV-4 inactivated antigen is 0.5-1.5: 2-3: 4-6: 1-2.
However, it would have been prima facie obvious before the effective filing date of the claimed invention to optimize the volume ratios of the four serotypes of inactivated antigens because Hou teaches that “[a]n ideal dengue vaccine should confer effective and balanced protection against all four dengue serotypes to minimize [antibody-dependent enhancement] ADE” (Introduction ¶3). This is further evidenced by Kirkpatrick, which teaches that the ideal ratios of dengue antigens are not expected to be 1:1:1:1 as at least DENV-2 requires a higher concentration for sufficient seroconversion and balanced protection against infection (Discussion ¶1).
Taken together, Hou and Kirkpatrick provide a clear, teaching, suggestion, and motivation to determine the optimal ratio of the four dengue serotypes. The optimal ratio of all serotypes advantageously prevents ADE as altering the amount of antigen has been shown in the art to change the immune response. As ADE occurs when the immune response is skewed and unbalanced, protection against dengue requires a balanced immune response to all four dengue serotypes. Adjusting the ratio of dengue antigens within a vaccine to create an equal immune response to all four serotypes would be advantageous in protecting against dengue infection and ADE.
Regarding claim 2, Thomas further discloses that the tetravalent inactivated dengue vaccine can include other components other than solely the antigens as Thomas included an adjuvant in their vaccine formulation. It would have been obvious to someone with ordinary skill in the art to perform routine optimization to determine the ideal ratio of antigens to other vaccine components.
Claims 4-10 recite various steps for preparing the claimed tetravalent dengue inactivated vaccine. Claims 4-10 were interpreted herein as product-by-process claims.
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
“The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by-process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing a nonobvious difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803, 218 USPQ 289, 292-33 (Fed. Cir. 1983).
Here, the claims are drawn to a tetravalent dengue inactivated vaccine, and not a method for making the same. As such, for purposes of applying prior art, claims 4-10 were broadly interpreted to encompass any tetravalent dengue inactivated vaccine having the claimed volume ratio 0.5-1.5: 2-3: 4-6: 1-2 (DENV-1: DENV-2: DENV-3: DENV-4). As discussed above, the combination of Thomas, Kirkpatrick, and Hou teaches the claimed tetravalent dengue inactivated vaccine and, therefore, in the absence of evidence to the contrary, claims 4-10 are reasonably encompassed by Thomas, Kirkpatrick, and Hou.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Thomas, Hou, and Kirkpatrick as applied to claims 1, 2, and 4-10 above, and further in view of "Helpful ELISA Hints" published by BIO-RAD (https://www.bio-rad-antibodies.com/helpful-elisa-hints.html, with WayBack Machine Publication date of 21 July 2017 having the link: https://web.archive.org/web/20170721012536/https://www.bio-rad-antibodies.com/helpful-elisa-hints.html, accessed on 17 November 2025, hereinafter "BIO-RAD").
As discussed above, claim 1, 2, and 4-10 were rendered prima facie obvious over Thomas, Hou, and Kirkpatrick. Claim 3 recites that the “coating quantities of the DENV-1 inactivated antigen, DENV-2 inactivated antigen, DENV-3 inactivated antigen, and DENV-4 inactivated antigen each are in a range of 1.00 microgram per well (µg/well) to 1.50 µg/well.”
The references do not teach the coating quantities of DENV-1 – 4 inactivated antigens being in a range of 1.00 – 1.50 µg/well. However, BIO-RAD teaches that “typical coating conditions involve adding 50-100µl of coating buffer, containing antigen or antibody at a concentration of 1-10 µg/ml” (7. Coating). This translates to 0.1 – 1.0 µg/well of antigen. The prior art end point overlaps with the instant claim. In the case where the claimed ranges “overlap or lie inside ranges disclosed in the prior art,” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Moreover, it would have been further obvious to one skilled in the art at the time of filing to combine the prior art as there is a reasonable expectation of success since the prior art establishes typical coating concentrations for ELISA coating and antigen immobilization.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Conclusion
NO CLAIMS ARE ALLOWED
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Cassandra Senn Grizer whose telephone number is 571-272-2292. The examiner can normally be reached M-Th 0630 - 1700 ET.
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/CASSANDRA SENN GRIZER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672