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 . 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.
Claim Rejections - 35 USC § 103 - Obviousness
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.
Claim(s) 1-4, 6-11 and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (US 2022/0081478 A1).
Kin taught a stable liquid pharmaceutical formulation (e.g., reads on a mixture of ingredients; reads on the instant claims 8 and 15) [0032, 0041, 0062-0063, 0072] comprising an antibody, and uses thereof [abstract]. Specifically, Kim taught a pharmaceutical formulation comprising: about 100 mg/ml of adalimumab (e.g., reads on an anti-TNFα antibody); a buffer comprising phosphate; mannitol as an excipient [see Table 12]; and polysorbate 20 as a surfactant [see again Table 12], wherein the pH was 5 to 7 [claim 1].
Claims 1, 8 and 15 are rendered prima facie obvious over the teachings of Kim, because it is prima facie obvious to combine prior art elements according to known methods, in order to yield predictable results. In the instant case, all the claimed elements (e.g., formulation of an anti-TNFα antibody, buffer, excipient, surfactant) were known in the prior art (e.g., Kim) and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would yield nothing more than predictable results (e.g., a pharmaceutical formulation comprising an antibody) to one of ordinary skill in the art. MPEP 2143.A.
The instant claims 1, 8 and 15 recite 80 mg/mL to 200 mg/mL antibody; pH of 4 to 7.5.
Kim taught an antibody at 100 mg/mL, and a pH of 5 to 7. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Kim reads on claims 1-2, 4, 7-9, 11 and 14-15.
Claims 3 and 10 are rendered prima facie obvious because Kim taught 4.1 mM to 12 mM succinate buffer [claim 7].
The instant claims 3 and 10 recite succinate buffer at 10 mM or 20 mM. Kim taught 4.1 mM to 12 mM succinate buffer. A prima facie case of obviousness exists because of overlap, as discussed above.
Claims 6 and 13 are rendered prima facie obvious because Kim taught polysorbate 20 at 0.01 % (w/v) to 0.2 % (w/v).
The instant claims 6 and 13 recite polysorbate 20 at a concentration of 0.01 % to 0.1 % (w/v). Kim taught polysorbate 20 at 0.01 % (w/v) to 0.2 % (w/v). A prima facie case of obviousness exists because of overlap, as discussed above.
Claim(s) 5 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Kim et al (US 2022/0081478 A1), in view of Manning et al (US 2014/0186361 A1).
The 35 U.S.C. 103 rejection over Kim was previously described.
Additionally, Kim taught mannitol from about 1 % (w/v) to about 10 % (w/v) [0060], and an aqueous medium [0025].
Kim did not teach glycerol, as recited in claims 5 and 12.
Manning taught stable aqueous formulations of adalimumab [title and abstract], comprising, as excipients, glycerol and mannitol [0296], at between 0.001 to 5 weight percent [0298].
Since Kim taught aqueous formulations of adalimumab, generally comprising excipients, it would have been prima facie obvious to one of ordinary skill in the art to include, within the teachings of Kim, glycerol at between 0.001 to 5 weight percent, as taught by Manning. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. In the instant case, it is prima facie obvious to select glycerol for incorporation into an aqueous formulation of adalimumab, based on its recognized suitability for its intended use as an excipient, as taught by Manning.
The instant claims 5 and 12 recite 8.25 mM to 14 mM mannitol and 217 mM to 272 mM glycerol.
Kim taught 54.9 mM to 549 mM mannitol. Manning taught 0.108 mM to 540 mM glycerol. A prima facie case of obviousness exists because of overlap, as discussed above.
The Examiner notes the following:
Kim’s teachings of 1-10 % mannitol is 54.9 to 549 mM.
This calculation is based on the following:
A 10% w/v solution contains 10 grams of mannitol per 100 mL of solution (or 100 grams per liter).
The molecular weight of mannitol is 182.17 grams per mole (g/mol).
To calculate the molarity (moles per liter):Molarity = (Mass of solute) ÷ (Molecular weight of solute × Volume of solution)
Molarity = (100 g) ÷ (182.17 g/mol×1 L) ≈ 0.54899 mol/L
Converting this to millimolar (mM) (1 M = 1000 mM):0.54899 M × 1000 ≈ 549 mM
The Examiner notes that the conversion of 1 % mannitol to mM is calculated as similarly as the 10 % endpoint, to result in 54.9 mM mannitol.
Manning’s teachings of 0.001-5 % glycerol is 0.108 mM to 540 mM.
This calculation is based on the following:
Molar mass of glycerol (C3H8O3): 92.09g/mol
Density of water: 1.0g/mL
A 0.001 wt.% solution is 0.001g of glycerol in every 100g of the total solution.
The mass of
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100g corresponds to a volume of 100mL (or 0.1L).
Moles of glycerol = (mass) ÷ (molar mass) = (0.001g) ÷ (92.09g/mol) ≈ 1.086×10-5 mol
Molar concentration of glycerol = (moles) ÷ (volume) = (1.086×10-5 mol) ÷ (0.1 L) ≈ 1.086×10-4 mol
Conversion to millimolar = Millimolarity (mM) = 1.086×10-4 M×1000 ≈ 0.1086mM
The Examiner notes that the conversion of 5 % glycerol to mM is calculated as similarly as the 0.001 % endpoint, to result in 540 mM glycerol.
Conclusion
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/CELESTE A RONEY/Primary Examiner, Art Unit 1612