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 .
DETAILED ACTION
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.
Status of the Claims
Claims 1-31 are currently pending.
Claim 1-31 have been considered on the merits.
Drawings
The disclosure is objected to because of the following informalities:
The drawings are objected to because of the following informalities: there is description of color in the Specification of Fig. 4 in 0027-0028 and Fig. 5 in 0029, and the various colors cannot be distinguished from each other since the figures are in black and white.
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.
Specification
The disclosure is objected to because of the following informalities: the use of trademarks.
The use of the terms: FreeStyle™ F-17 in 0068-0069; Kolliphor® P188 in 0068; Beckman Coulter Vi-Cell™ Viability Analyzer in 0068; PEI MAX® reagent in 0069; KingFisher® purification in 0069 and 0071; Twist Bioscience® in 0070; Milli-Q® water in 0071; and Caliper LabChip® GXII Touch instrument in 0072, which are a trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
The disclosure is objected to because of the following informalities:
Claim 1 is objected to missing the conjunction “and” after the phrase “fresh cell culture media” in line 10, and in the interest of improving claim form, it is suggested that the word “and” be added. In other words, “and” needs to be include between steps (c) and (d).
Claim 16 is objected to missing the conjunction “and” after the phrase “fresh cell culture media” in line 10, and in the interest of improving claim form, it is suggested that the word “and” be added. In other words, “and” needs to be include between steps (c) and (d).
Appropriate correction is appreciated.
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.
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 1-30 are rejected under 35 U.S.C. 103 as being unpatentable over Jäger et al. (BMC Biotechnology, 2013) (ref. of record) as evidenced by Heng et al. (Antibody Therapeutics, Jan. 10, 2022).
With respect to claims 1 and 16, Jager teaches a method for transfecting a population of mammalian cells with DNA encoding a target molecule (abstract).
With respect to step (a) of claims 1 and 16, Jager teaches providing the cells in a cell culture medium (pg. 12-13 bridging para.).
With respect to step (b) of claims 1 and 16, Jager teaches that the transfection of DNA in HEK293 cells can be performed by cationic liposomes and polymers (pg. 2 Col. 2 para. 1). Specifically, Jagar teaches contacting HEK293 cells with DNA/PEI (polyethylenimine) complex where there is 10 µg of DNA (pg. 16 Col. 1 para. 3) and contacting HEK293-6E cells with PEI and DNA complex where there is 1 µg of DNA (pg. 16 Col. 1-2 bridging para.). Although, Jager teaches performing a transfection step by contacting the cells with a cationic polymer/DNA complex (pg. 16 Col. 1 para. 3 to Col. 2 para. 1), it would have been obvious to one of ordinary skill in the art to modify Jager to use a cationic liposome instead. At the time of the claimed invention, one of ordinary skill in the art would have been motivated to modify the teachings of Jagar in such a way that the transfection is performed with a cationic liposome for the purpose being able to transfect the cells. Furthermore, it would have been obvious to one skilled in the art to have further modified Jager such that transfection is performed with a cationic liposome, since methods of transfecting cells, including HEK293 cells, were known to use cationic liposomes as taught by Jager. Such a modification merely involves the substitution of one known type of cationic transfection reagent for another for the transfection of cells.
Jagar is silent with respect to the mg DNA:cell number ratio and does not teach that it is about 0.25 mg: 1x 109 cells as recited in step (b) of claims 1 and 16. Even though Jager does not teach the mg DNA:cell number ratio recited in claims 1 and 16, one of ordinary skill in the art would recognize that the mg DNA:cell number ratio in a transfection is a result effective variable and that the mg DNA:cell number ratio would be matter of routine optimization depending as evidenced by Heng. Heng reports optimizing recombinant antibody production through transfection and culture conditions (abstract). Heng reports that transfection parameters that are optimized include seeding cell density and DNA concentration (pg. 31 Col. 1 para. 2).
With respect to step (c) of claims 1 and 16, Jager teaches 48 hours after transfection adding one volume of fresh cell culture medium with 0.5% Tryptone NI, and then adding glucose 3 days (72 hrs) after the transfection (Fig. 6 and Fig. 8 legends, pg. 8 Col. 1 last para. and pg. 17 Col. 2 para. 1). Jager further teaches the method where the glucose in the medium for the HEK293 cells is 4.5 g/L (pg. 13 Col. 1).
Jager does not teach the method where 2-6 hours after the transfection these components are added to the cell culture as recited in step (c) of claim 16. Similarly, Jager does not teach the method where 4 hours after the transfection these components are added to the cell culture as recited in claim 28. Although Jager does not teach same timing as claimed for the addition of fresh cell culture medium, Tryptone NI and glucose, one of ordinary skill in the art would recognize that this timing is a result effective variable and that the timing would be matter of routine optimization as evidenced by Heng. Heng reports optimizing recombinant antibody production through transfection and culture conditions (abstract). Heng reports culture parameters that are optimized include medium replacements, serum deprivation, use of cell line maintenance antibiotic, incubation temperature, culture volume, harvesting time and nutrient supplementation (pg. 31 Col. 1 para. 2).
With respect to step (d) of claims 1 and 16, Jager teaches harvesting the supernatant after 5 to 6 days (120-144) (Fig. 8 legend). In addition, with respect to step (d) of claims 1 and 16, Jager teaches ScFv-Fc-RNase (a target molecule) was purified from supernatants harvested 8 days (192 hrs) after transfection (Fig. 6 legend). Although Jager does not teach the exact ranges recited in claims 1 and 16 for the time of harvesting of the target molecule, the ranges overlap significantly with the ranges taught. Furthermore, one of ordinary skill in the art would recognize that the harvesting time of the target molecule is a result effective variable and that the harvesting time would be matter of routine optimization as evidenced by Heng. Heng reports optimizing recombinant antibody production through transfection and culture conditions (abstract). Heng reports culture parameters that are optimized include harvesting time (pg. 31 Col. 1 para. 2).
With respect to claims 2-5 and 17-20, Jager teaches the method where cells are HEK293-6E suspension cells and HEK293 adherent cells (abstract and pg. 12-13 bridging para.).
With respect to claims 6 and 21, Jager teaches seeding 5 x 105 cells/ml prior to transfection (pg. 16 Col. 1 last para.).
Jager does not teach seeding the cells at a concentration of 1 x 106 cells/ml as recited in claims 7 and 22. Although Jager does not teach the exact seeding concentration of cells recited in claims 7 and 22 for seeding, one of ordinary skill in the art would recognize that the concentration of cells that are seeded prior transfection is a result effective variable and that the timing would be matter of routine optimization depending on such factors as the desired confluency at the time of transfection, when the transfection is being performed, and the cell type and as evidenced by Heng. Heng reports optimizing recombinant antibody production through transfection and culture conditions (abstract). Heng reports that transfection parameters that are optimized include seeding cell density and volume (pg. 31 Col. 1 para. 2).
With respect to claims 8 and 23, Jager teaches the concentration of Tryptone N1 is 0.5% (5 g/L) (Fig. 6 and Fig. 8 legends, pg. 8 Col. 1 last para. and pg. 17 Col. 2 para. 1).
With respect to claims 9 and 24, Jager teaches the method where the concentration of glucose is 4.5 g/L (pg. 13 Col. 1).
With respect to claims 10 and 25, Jager teaches one volume of fresh cell culture medium is added (Fig. 6 and Fig. 8 legends, pg. 8 Col. 1 last para. and pg. 17 Col. 2 para. 1).
With respect to claims 11, 12, 26 and 27, Jager teaches the method where valproic acid is added 3 days (72 hours) after the transfection at a final concentration of 3.75 mM (Fig. 6 legend).
Jager does not teach the method where the valproic acid is added 88-104 hours after transfection as recited in claims 11 and 26. Similarly, Jager does not teach the method where the valproic acid is added about 96 hours after transfection as recited in claims 15 and 30. Although Jager does not teach the range of time of when the valproic acid is added after transfection recited in claims 11 and 26 for seeding, one of ordinary skill in the art would recognize that the timing of the addition of the valproic acid after transfection is a result effective variable and that the timing would be matter of routine optimization depending on such factors as the cell type, the cell density and the molecule being produced and as evidenced by Heng. Heng reports optimizing recombinant antibody production through transfection and culture conditions (abstract). Heng reports culture parameters that are optimized include medium replacements, serum deprivation, use of cell line maintenance antibiotic, incubation temperature, culture volume, harvesting time and nutrient supplementation (pg. 31 Col. 1 para. 2).
With respect to claim 13, Jager teaches step (c) is performed 48 hours after the transfection (Fig. 6 and Fig. 8 legends, pg. 8 Col. 1 last para. and pg. 17 Col. 2 para. 1).
With respect to claims 14 and 29, Jager teaches step (d) is performed 8 days (192 hours) after transfection (Fig. 6 legend). Jager does not teach the method where step (d) is performed 168 hours after transfection as recited in claims 14 and 29. Although Jager does not teach the exact ranges recited in claims 1 and 16 for the time of harvesting the target molecule after transfection, one of ordinary skill in the art would recognize that the harvesting time of the target molecule is a result effective variable and that the timing would be matter of routine optimization as evidenced by Heng. Heng reports optimizing recombinant antibody production through transfection and culture conditions (abstract). Heng reports culture parameters that are optimized include harvesting time (pg. 31 Col. 1 para. 2).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claim 31 is rejected under 35 U.S.C. 103(a) as being unpatentable over Jager as evidenced by Heng (as applied to claims 1-30 above), and further in view of Estes et al. (iScience, 2021).
The teachings of Jager can be found in the previous rejection above.
Jager does not teach the method where the target molecule is a multispecific antigen binding protein as recited in claim 31.
However, Estes teaches a similar method of transfecting HEK293 cells with DNA encoding a target molecule where the target molecule is a multispecific antigen binding protein (abstract, pg. 17 para. 4, and pg. 18 para. 3). Estes further teaches that bispecific antibodies have new therapeutic functionalities compared to monoclonal antibodies (pg. 2 para. 1).
Accordingly, at the effective time of filing of the claimed invention, one of ordinary skill in the art would have been motivated to modify the method of transfecting a population of mammalian cells of Jager to include transfecting a DNA encoding for a multispecific antigen binding protein for the benefit of being able to produce additional useful therapeutic target molecules as taught by Estes. It would have been obvious to one of ordinary skill in the art to make such a modification to Jager, since similar methods of transfecting mammalian cells such as HEK293 cells for the expression and harvesting of multispecific antigen binding proteins was known as taught by Estes. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in making such a modification to Jager, since Estes teaches a similar transfection method using mammalian cells.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached on 571-272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632
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