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 .
Priority
The present application is a § 371 National Stage entry of PCT/US2023/018527 (filed on 04/13/2023) which claims benefit of U.S. provisional application 63/331,059 (filed on 04/14/2022).
Claim Status
Claims 1-23 are currently pending and have been examined on their merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/30/2024 is in compliance with the provisions of 37 C.F.R. 1.97. All references cited in this IDS have been fully considered.
Drawings
The drawings are objected to because they improperly present multiple views.
Specifically, the drawing standards require that “[p]artial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation "FIG." (37 CFR § 1.84(u)(1)). Accordingly, the views of FIG. 1 should be amended to FIG. 1A, FIG. 1B, FIG. 1C, and FIG. 1D.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 1 is objected to because the article “a” should be added before “test molecule”.
Claims 2-9, 11, and 13-23 are objected to because the word “claim” is not a proper noun and should not be capitalized.
Claim 9 is objected to because the abbreviation “EMD” should be fully defined when first used in the claims. Based upon applicant’s specification, it appears that this refers to “EMD Millipore” (specification, [0037]). For the reasons discussed below in the Examiner’s Note, although these claims have not been treated on their merits, the use of these trademarks and trade names are improper and they should not be present in the claim listing.
Claims 8-9 and 18 are objected to because “Bio-Rad”, “Cedarlane”, and “EMD” are trademarks and/or tradenames and should be accompanied by the appropriate trademark symbols. For the reasons discussed below in the Examiner’s Note, although these claims have not been treated on their merits, the use of these trademarks and trade names are improper and they should not be present in the claim listing.
Claims 7-9 and 17-23 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims 7-9 and 17-23 have not been further treated on the merits.
Appropriate correction is required.
Examiner’s Note
Claims 8-9 and 18 have not been treated on the merits because they are in improper multiple dependent form. In the interest of prosecution, it is noted that these claims are improper under 35 U.S.C. § 112(b) because they use a trademark or trade name to identify a source of goods. If the trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of the 35 U.S.C. 112(b)(MPEP § 2173.05(u)). For example, each of the listed companies could change the identity of their complement and it is therefore unclear which structures are actually covered by the scope of the claims. Additionally, it is unclear what the structure of “complement from Bio-Rad” (or EMD or Cedarlane) is or how it differs structurally from complement acquired elsewhere.
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.
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.
Claims 1-6, 10, and 12-16 are rejected under 35 U.S.C. 103 as being unpatentable over Duensing et al. (Cold Spring Harbor Protocols, 2018, Vol. 2, pages 135-137; cited in IDS filed on 10/30/2024).
Duensing teaches that a useful feature of therapeutic antibodies is the ability to kill the cells to which they bind and antibodies are capable of mediating cell killing in a variety of ways (abstract). Among these is complement-mediated mechanisms (Id.). Duensing teaches that extensive, multidose characterizations of a series of candidates can be performed in a short amount of time using assays developed for high-throughput flow cytometry (Id.)
Regarding claims 1-6, Duensing teaches a complement-dependent cytotoxicity assay (see protocol title). Duensing teaches a step of preparing cells by detaching (if adherent), washing with PBS, centrifuging, resuspending, filtering, counting, and seeding into a clear U-bottom 96-well tissue culture-treated plate (p. 136, “Cell Preparation”). Duensing then teaches a step of adding complement source and test antibody (i.e., test molecule; see [0027] of the specification) at various concentrations to each well. Although Duensing does not specify the order of addition (i.e., if complement is added to cells + test molecule or if test molecule is added to cells + complement), it would have been obvious to have arrived at either solution. See MPEP § 2144.04(IV)(C) which states that “selection of any order of mixing ingredients is prima facie obvious. Accordingly, Duensing at least renders obvious a method of performing a complement-dependent cytotoxicity assay comprising adding complement to a mixture of target cells and test molecule.
Duensing differs from claims 1-6 because it does not teach that the speed of complement addition is at least 250 µL/s, at least about 400 µL/s, about 400 µL/s, about 450 µL/s, about 500 µL/s, and at least about 500 µL/s, respectively.
Nonetheless, a person having ordinary skill in the art could have arrived at these speeds as a result of routine experimentation. Duensing does not provide any particular rate of complement addition and therefore a person having ordinary skill in the art would have been prompted to experiment with various speeds in order to arrive at an optimal speed for performing the prior art assay such as in order to find a balance between a need for “extensive, multidose characterization of a series of candidates…in a short amount of time” (abstract) and for ensuring accurate assay results. There is no evidence of record that the claimed ranges of addition speeds elicit an unexpected or remarkable result over the breadth of the claims. In other words, the CDC assay is well-established in the art and merely determining optimal reaction conditions (absent evidence of criticality) remains prima facie obvious (MPEP § 2144.05(II)(A)).
Thus, claims 1-6 are considered to be obvious over Duensing as a result of routine experimentation.
Regarding claim 10, as discussed above, Duensing renders obvious a method of performing a complement-dependent cytotoxicity assay comprising mixing complement, target cells, test molecule, and media. Although Duensing does not specify the order of addition (i.e., if target cells and test molecule are added to a mixture comprising complement and media or some other order of steps), it would have been obvious to have arrived at either solution. See MPEP § 2144.04(IV)(C) which states that “selection of any order of mixing ingredients is prima facie obvious.
Thus, claim 10 is obvious over Duensing.
Regarding claims 12-16, as discussed above, Duensing renders obvious a method of performing a complement-dependent cytotoxicity assay comprising mixing complement, target cells, and a test molecule. Duensing differs from claims 12-16 because it does not teach that the speed of complement addition is at least 250 µL/s, at least about 400 µL/s, about 400 µL/s, about 450 µL/s, and at least about 500 µL/s, respectively.
Nonetheless, a person having ordinary skill in the art could have arrived at these speeds as a result of routine experimentation. Duensing does not provide any particular rate of complement addition and therefore a person having ordinary skill in the art would have been prompted to experiment with various speeds in order to arrive at an optimal speed for performing the prior art assay such as in order to find a balance between a need for “extensive, multidose characterization of a series of candidates…in a short amount of time” (abstract) and for ensuring accurate assay results. There is no evidence of record that the claimed ranges of addition speeds elicit an unexpected or remarkable result over the breadth of the claims. In other words, the CDC assay is well-established in the art and merely determining optimal reaction conditions (absent evidence of criticality) remains prima facie obvious (MPEP § 2144.05(II)(A)).
Thus, claims 12-16 are considered to be obvious over Duensing as a result of routine experimentation.
Claims 1-6 and 10-16 are rejected under 35 U.S.C. 103 as being unpatentable over Duensing et al. (Cold Spring Harbor Protocols, 2018, Vol. 2, pages 135-137; cited in IDS filed on 10/30/2024) in view of Offner et al. (WO 2016/096788 A1; cited in IDS filed on 10/30/2024).
The teachings of Duensing are set forth above and applied herein. Duensing is found to render obvious claims 1-6, 10, and 12-16.
Regarding claim 11, as discussed above, Duensing teaches addition of “complement source (Human AB serum)” (p. 136, “Killing Assay”). Accordingly, Duensing differs because it does not teach that the complement is baby rabbit complement.
Nonetheless, Offner also teaches improved CDC assays (abstract) and specifically teaches that “[i]t has been found that for determining complement dependent cytotoxicity of a composition that comprises molecules that on one hand specifically bind to one or more cell surface antigens and the on the other hand comprise an Fc-region polypeptide of human origin… a non-syngeneic complement has to be used’’ (p. 14, lines 3-11). For example, Offner provides an assay showing CDC-mediated killing of BT-474 cells by anti-HER2 antibodies (Example 6). Said method comprises seeding 10,000 BT-474 cells on 96-well plates and adding 50 µL baby rabbit complement, followed by measuring cell index every 5 minutes (p. 38, lines 3-11). Offner summarizes these findings by stating “[i]t has been surprisingly found that the combination of human cancer cells, a human or humanized antibody and a non-syngeneic complement of rabbit origin results in a functional assay (p. 15, lines 18-20).
Thus, because Duensing provides a generic CDC assay protocol involving addition of 50 µL of Human complement source and because Offner teaches that the use of baby rabbit complement results in a functional assay and in some cases is required in order to arrive at a functional assay. As such, it would have been obvious to have simply substituted Duensing’s “complement source” with Offner’s baby rabbit complement. The function of Human AB serum and baby rabbit complement were both known in the art at the time of filing and the result of the substitution would have been a functional CDC assay which is capable of testing cells such as cancer cells, as discussed by Offner. This obviousness is based upon the “Simple Substitution of One Known Element for Another to Obtain Predictable Results” rationale set forth in in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
Thus, claim 11 is obvious over Duensing in view of Offner.
Conclusion
No claim is allowed.
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/GRANT C CURRENS/Examiner, Art Unit 1651
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