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
1. The Amendment filed November 03, 2025 in response to the Office Action of August 06, 2025 is acknowledged and has been entered. Claims 1-31 and 33-38 have been cancelled. Claim 32 had been amended.
2. Claim 32 is currently being examined.
Rejections Maintained
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.
3. Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over US 2013/0034559 A1 (Queva et al. Feb. 7, 2013), “Queva” in view of US 2006/0088523 A1 (Andya et al. Apr. 27, 2006), “ Andya” for the reasons of record set forth below.
Queva teaches human monoclonal antibodies against B7-H1/PD-L1. See abstract and ¶¶ 0005 and 0012.
Queva teaches the anti- B7-H1/PD-L1 comprises the light chain of SEQ ID NO: 77 which comprises the currently claimed SEQ ID NOs: 3 and 8-10. See c ¶¶ 0084-0085 and claim 36 and Appendix.
Queva teaches the anti- B7-H1/PD-L1 comprises the heavy chain of SEQ ID NO: 72 which comprises the currently claimed SEQ ID NOs: 4-7. See ¶¶ 0084-0085 and claim 36 and Appendix.
MEDI4736 comprises SEQ ID NOS: 3-10. See p. 6-lines 11-15 of the instant specification.
Queva teaches liquid therapeutic formulations for the antibodies of the invention. See ¶¶ 0291-0303. Queva teaches therapeutic the antibody formulations can contain buffers, amino acids, disaccharides, surfactants like Tween. See ¶ 0295.
Queva teaches as set forth above, but does not teach the all of the specific concentrations and components of the formulation claimed.
Andya teaches antibody formulations off histidine-acetate, pH 5.5 to 6.5 that retard antibody degradation. See abstract and ¶¶ 0042-0043.
Andya teaches the antibody formulations are liquid. See ¶¶ 0401-0403.
Andya teaches antibody buffer formulations with histidine buffers including histidine HCl and histidine acetate. See ¶¶ 0101, 0417, 0423-427, and 0436-0440.
Andya teaches histidine HCl and histidine acetate buffers reduce the formations of insoluble aggregates of antibodies in the buffered solutions. See ¶¶ 0423-0427 and Fig. 10.
Andya teaches that the antibody can be in amounts 10 mg/mL to about 250 mg/mL or 20 mg/mL to about 40 mg/mL See ¶¶ 0045 and 0048.
Andya teaches that the histidine buffer can be in the concentrations, preferably, from about 10 mM to about 40 mM or most preferably about 20 mM. See ¶¶ 0370 and 0423-0429.
Andya teaches that the saccharide in the formulations can be selected from the group consisting of trehalose and sucrose, in an amount from about 10 mM to about 1 M or from about 60 mM to about 250 mM. ¶¶ 0045, 0102, 0359, 0375, 0473, and 0486.
Andya teaches using trehalose dihydrate in the formulations. See ¶ 0486.
Andya teaches using polysorbate 20 and polysorbate 80 in the formulations as a surfactant at a concentration preferably from about 0.01% to about 0.1%, for example about 0.02% . See ¶¶ 0103, 0376 and 0417.
Andya teaches the use of polysorbate 20 in histidine-HCl and sucrose formulation effectively prevented formation of insoluble particulates.. See ¶¶ 0430-0440.
Andya teaches Pertuzumab formulated into 20 mM histidine-acetate buffer with 120 mM sucrose and 0.02% polysorbate 20 was the most stable around pH 6.0. See ¶ 0416.
Andya teaches that the formulations are aqueous formulations that may be frozen or lyophilized. See ¶¶ 0052, 0091, 0374 and 0382.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Queva and Andya use histidine/histidine HCl, disaccharides like trehalose dihydride, and surfactants like polysorbate 20 and polysorbate 80 in the formulations at around pH 6 for the anti- B7-H1/PD-L1 antibodies of Queva because Queva teaches formulating the antibodies for therapy and Andya teaches that each of these components can improve solubility and stability of the antibodies in formulation solutions. One would have been motivated to adjust the concentrations of the various components of the antibody formulations and pH of the formulation to optimize the stability and solubility of the antibodies in the formulations.
Response to Arguments
4.
PNG
media_image1.png
138
720
media_image1.png
Greyscale
PNG
media_image2.png
890
657
media_image2.png
Greyscale
PNG
media_image3.png
851
675
media_image3.png
Greyscale
PNG
media_image4.png
882
677
media_image4.png
Greyscale
PNG
media_image5.png
217
645
media_image5.png
Greyscale
Applicant's arguments have been considered, but have not been found persuasive. With regard to the predictability of making liquid formulation of the antibody, as set forth above both Queva and Andya teach making liquid antibody formulations. Additionally, as previously set forth and above Andya teaches that the antibody can be in amounts 10 mg/mL to about 250 mg/mL. Thus, it is not unpredictably to make liquid antibody formulation with an antibody concentration of 50 mg/ml in view of Queva and Andya.
With regard to the teachings of Warne, Warne teaches that in addition to a liquid formulation of adalimumab at 50 mg/ml, Warne teaches a liquid formulation of Ustekinumab at 90 mg/ml and golimumab at 100 mg/ml. See Table 1. Thus, Warne does not teach high concentration liquid antibody formulations are unpredictable.
Additionally, Warne teaches that to save time and effort teach that many laboratories use “platform formulations” in which a suitable high concentration, robust formulations are broadly used for early stage biologics to increase efficiency. See abstract.
Warne teaches additionally teaches that the pH range for higher concentration antibodies is 6.0 + 0.4 and that the six most highly concentrated antibodies use L-histidine as the buffer. See p. 209-right column-1st full paragraph. Warne teaches that since most of the high concentration antibodies are formulated at a pH of 6.0 + 0.4 making high concentration formulations outside of this range does not appear to be of value. Warne teaches Thus, given that L-histidine has a pKa of 6.0 using L-histidine as the buffer is a logical choice. See p. 209-right column-last paragraph.
Warne teaches additionally teaches that 16 of 21 antibody formulations use either polysorbate 20 or 80. Warne teaches given that broad use of polysorbate 20 or 80 they recommend including polysorbate 20 or 80 at a level suitable to that required by the protein concentration. See p. 209-right column-2nd and 3rd paragraphs.
Given the teaching Queva, Andya and Warne, the art shows that rather than being unpredictable, the making of stable liquid antibody formulations was predictable for one of skill in the art at the time the invention was filed. Thus, the rejection is maintained for the reasons previously set forth above.
Conclusion
5. All other objections and rejections recited in the Office Action of August 06, 2025 are withdrawn in view of Applicant’s amendments and arguments.
6. No claims allowed.
7. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached on M-F 8:30-5:30 Eastern Time
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, Janet L Epps-Smith can be reached on 571-272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Peter J Reddig/
Primary Examiner, Art Unit 1642