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
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-12 and species: 80 mg/mL to 300 mg/mL, 100 mM to 400 mM, 0.01% w/v to 0.1%, arginine hydrochloride, histidine buffer, and 10 to 100 mM as the histidine buffer concentration in the reply filed 09/26/2025 is acknowledged.
Claims 1-5, 7-12, and new claims 22-38 are now under consideration in the instant Office Action.
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.
Claims 1-5, 7-11, and 22-38 are rejected under 35 U.S.C. 103 as being unpatentable over Luthman et al. (in WO 2020/023530 A2, in IDS filed 09/19/2022), in view of Morichika et al. (US 2016/009419 A1, in instant PTO-892)
Luthman et al. teaches “methods comprising administering a composition comprising a therapeutically effective amount of at least one anti-Aβ protofibril antibody... In some embodiments, the at least one anti-Aβ protofibril antibody is BAN2401”, see Abstract. Luthman et al. teach an antibody referred to as “BAN2401”, which is a 100% sequence identity match to instant SEQ ID NOs: 1 and 2, as well as the antibody known as “lecanemab” and “Leqembi®”. Luthman et al. also teaches that the BAN2401 antibody can be supplied as any formulation suitable for administration to a human subject, for example, as a sterile, clear solution for injection containing 10 mg/mL, in a single-use 10 mL vial (total 100 mg/vial) comprising 25 mM sodium citrate, 125 mM sodium chloride, 0.02% (w/v) polysorbate 80, and having pH of 5.7 when administered intravenously, see paragraph 0689. This meets the limitations of instant claims 1 and 33 wherein the sequences to the anti-Aβ protofibril antibody are taught, instant claims 34-38 wherein the antibody taught in the reference is a match to the antibody referred to as “lecanemab” in the claims, instant claim 7 wherein the citrate buffer is 10 to 100 mM, instant claim 12 wherein the citrate buffer is 30 to 50 mM, and instant claims 1, 11, 12, 22, 33, 34, 35 wherein the pH ranges from 4.5 to 5.5.
However, Luthman et al. does not teach a high concentration antibody formulation. Morichika et al. remedies this deficiency.
Morichika et al. teaches “antibody-containing formulation, and particularly, to a stable liquid formulation containing a high concentration of an antibody”, see paragraph 0001. Morichika et al. discuss the constraints on creating a high concentration antibody formulation for administration, teaching that “designing an antibody-containing formulation for subcutaneous injection, since a dose of an antibody per administration is large (about 100 mg to 200 mg) and an amount of an injection solution is generally limited in subcutaneous injection, it is necessary to increase a concentration of an antibody in a liquid to be administered. In view of this, in many cases, high concentration formulations are used, which are prepared by the lyophilization-concentration technique, in which a lyophilized formulation is reconstituted in water having a volume smaller than that before lyophilization. However, a strong demand exists for a liquid formulation which does not require reconstitution, and which is easy to handle”, see paragraph 0003.
Morichika et al. teach a high concentration antibody dosage of “preferably has an antibody concentration of not less than 50 mg/mL, more preferably not less than 100 mg/mL, still more preferably not less than 120 mg/mL, and yet more preferably not less than 150 mg/mL. It should be noted that a liquid formulation containing antibody at a concentration of 120 mg/mL or higher, or preferably 150 mg/mL or higher, has not been developed for commercial use” with the “highest concentration of antibody in the liquid formulation according to the present invention may be typically 300 mg/mL, preferably 250 mg/mL and more preferably 200 mg/mL. Therefore, the antibody-containing liquid formulation according to the present invention preferably has an antibody concentration of from 50 to 300 mg/mL, more preferably from 100 to 300 mg/mL, still more preferably from 120 to 250 mg/mL, and yet more preferably from 150 to 200 mg/mL”, see paragraphs 0041-0042. This meets the limitations of instant claims 1 and 23 wherein the concentration of the anti-Aβ protofibril antibody is 80 mg/mL to 300 mg/mL, instant claims 2, 3, 4, 24, 25, 26, 33, 34, 35 wherein the concentration of the anti-Aβ protofibril antibody is 100 mg/mL to 200 mg/mL, instant claim 11 wherein the concentration of the anti-Aβ protofibril antibody is 80 mg/mL to 240 mg/mL, and instant claim 12 wherein the concentration of the anti-Aβ protofibril antibody is 80 mg/mL to 120 mg/mL.
Morichika et al. found that “in solutions in which a high concentration of antibody was dissolved a buffer solution containing the amino acid arginine, the amount of generated dimer was smaller than that in solutions to which arginine was not added. From these results, it was found that arginine is effective as a stabilizer for inhibiting dimerization. Further, in solutions in which a high concentration of antibody was dissolved in a buffer solution containing arginine and methionine, the inhibitory effect against dimerization was observed at a total concentration of arginine and methionine which is lower than the concentration of arginine alone needed for attaining the same inhibitory effect. From these results, it was found that a synergistic effect is obtained by the addition of arginine and methionine in combination”, see paragraph 0059. Morichika et al. found that an effective concentration for the “arginine concentration is 100 to 300 mM, and the methionine concentration is 10 to 50 mM”, see paragraph 0062. This meets the limitations of instant claim 1 wherein the arginine concentration is 100 mM to 400 mM, instant claim 5 wherein the formulation comprises methionine, instant claim 8 wherein the arginine concentration is 125 mM to 350 mM, instant claims 9 and 10 wherein the arginine concentration is 200 mM, instant claim 11 wherein the arginine concentration is 140 mM to 260 mM, instant claim 12 wherein the arginine concentration is 240 mM to 360 mM, instant claim 32 wherein the formulation comprises arginine, and instant claims 33, 34, 35 wherein the arginine concentration is 190 mM to 210 mM.
Morichika et al. teaches the use of polysorbate 80 as surfactants and stabilizers in the formulation wherein the concentration “is generally 0.0001 to 10% (w/v), preferably 0.001 to 5%, more preferably 0.005 to 3%”, see paragraph 0068. This meets the limitations of instant claim 1 wherein the polysorbate is at 0.01% w/v to 0.1% w/v, instant claim 11 wherein the polysorbate is at 0.02% w/v to 0.08% w/v, instant claim 12 wherein the polysorbate is at 0.02% w/v to 0.08% w/v, instant claim 33 wherein the polysorbate is at 0.04% w/v to 0.06% w/v, instant claim 34 wherein the polysorbate is at 0.05% w/v, and instant claim 35 wherein the polysorbate is at 0.05% w/v.
Morichika et al. teaches that the high concentration antibody formulation can have a pH range from 4 to 8, with more preferable embodiments including buffer solutions ranging from “5.0 to 7.5… A buffering agent which can be used in the present invention is one which can adjust the pH in this range and which is pharmaceutically acceptable”, see paragraph 0063. This meets the limitations of instant claims 1, 11, 12, 22, 33, 34, 35 wherein the pH ranges from 4.5 to 5.5.
Morichika et al. teaches “the high concentration antibody-containing liquid formulation according to the present invention, the buffer is preferably a histidine buffer or glycine buffer, and a histidine buffer is especially preferred. The concentration of the buffer solution is generally 1 to 500 mM, preferably 5 to 100 mM, still more preferably 10 to 20 mM”, see paragraph 0063. This meets the limitations of instant claims 1 and 23 wherein the formulation contains a pharmaceutically acceptable buffer, instant claims 7, 22, 27 wherein the histidine buffer is 10 to 100 mM, instants claims 10, 29, 34, 35 wherein the histidine buffer is 25 mM, instant claims 11, 28, 33 wherein the histidine buffer is 15 to 35 mM, instant claims 30 and 31 wherein the buffer is a histidine buffer.
It would be obvious at the time of the instant invention to use the high concentration of the anti-Aβ protofibril antibody known as “BAN2401” taught by Luthman et al., which is an antibody used as a treatment that results in the reduction of amyloid beta plaques related to Alzheimer’s Disease, with the formulation optimized for high concentration antibodies taught by Morichika et al., which uses routine optimization to find a suitable formulation for antibodies when they are needed for intravenous or subcutaneous administration. One would be motivated to combine the antibody with the formulation with the expectation of creating a “liquid formulation containing a high concentration of an antibody … with which reformulation by concentration by lyophilization is not necessary, and hence does not require reconstitution. The antibody-containing liquid formulation according to the present invention can be stored in a liquid state for a long time. Since the antibody-containing liquid formulation according to the present invention can be produced by a process not including a lyophilization step, addition of a sugar or the like as a cryoprotective agent is not necessary”, see paragraph 0030 of Morichika et al. This ensures the longevity of the antibody in formulation, success and ease of its administration to human subjects at high concentrations, and addresses common concerns of storing high concentration antibody formulations such as protein aggregation and protein loss overtime in varying conditions.
Therefore, claims 1-5, 7-12, and 22-38 are rejected as obvious over Luthman et al. and Morichika et al.
Conclusion
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/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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