DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-20 are pending and under consideration in this 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 of this title, 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 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over EP3037529 (06/29/2016; IDS filed 11/07/2024) in view of Chen et al. (Constitutive expression of recombinant human hyaluronidase PH20 by Pichia pastoris. Journal of Bioscience and Bioengineering. 2016, vol. 122, no. 6, pages 673-378; IDS filed 11/07/2024), Frost et al. (Recombinant human hyaluronidase (rHuPH20): an enabling platform for subcutaneous drug and fluid administration. Expert Opin. Drug Deliv. 2007, vol. 4, no. 4, pages 427-440; IDS filed 11/07/2024).
EP3037529 teaches host cells expressing human-derived pH20 hyaluronidase are cultured in a medium at 37°C and pH 7.2 for 14 days; an integral cell density increases with the culture period; 25% of sialic acid is contained; and an enzymatic activity is 1600 units/mL (see entire publication and abstract especially paragraphs [0322], [0327], [0328] and [0358] and Tables 10, 11, 12 and 28). The teachings of the reference differ from the claims in that the reference does not teach the recited method steps of lowering the culture temperature to 28-34 °C and the activity in a culture solution of the enzyme, is 10,000 unit/mL or more.
Chen et al. teach constitutive expression of recombinant human hyaluronidase PH20 in Pichia pastoris. Chen et al. teach a DNA fragment containing core domain of human PH20 gene was cloned into a constitutive expression plasmid (pGAPZαC) of Pichia pastoris to produce a fusion protein with α factor signal in the N-terminus and 6 × His as well as c-Myc tags in the C-terminus, where the resulting plasmid pGAPZαC-PH20 was integrated into the genome of P. pastoris strain GS115. Chen et al. teach that functional recombinant human PH20 (rHuPH20) was successfully expressed and secreted by the recombinant P. pastoris transformant after incubation for 2 days at 30°C; the highest hyaluronidase activity of 2 mU/mL could be obtained at 3 day in an YPD culture; and after purified by phenylboronic acid resin adsorption, rHuPH20 with a specific activity of 230 mU/mg was obtained. See entire publication and abstract especially MATERIALS AND METHODS section, RESULTS AND DISCUSSION section, and pages 674-677.
Frost et al. teach recombinant human hyaluronidase (rHuPH20) where its cDNA was cloned into a well-characterized mammalian cell line. Frost et al. teach that a commercially acceptable expression vector containing the human PH20 cDNA encoding amino acids 1 – 482 (rHuPH20) followed by a cytomegalovirus-driven bicistronic vector with the dihydrofolate reductase (DHFR) selection marker was constructed to allow for positive selection in DHFR-deficient CHO cells previously adapted to grow in chemically defined media without any animal-derived materials. Frost et al. teach that transfectants were cloned in chemically defined media and selected with increasing concentrations of methotrexate to produce a high level rHuPH20-secreting cell line. Frost et al. teach that a four-step column chromatographic downstream purification process was developed that resulted in a highly purified enzyme protein with a specific activity of over 100,000 USP Units/mg protein, where the process resulted in a 447 amino acid 61 kDa glycoprotein with a properly processed amino terminus and 6 N -linked glycosylation sites. See entire publication and abstract especially 2.2 Development of a manufacturing process for rHuPH20 section and pages 432-437.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of EP3037529 to include the methods steps as taught and/or suggested by Chen et al. and Frost et al. for production of recombinant protein including the human-derived pH20 hyaluronidase or any other variant including lowering the culture temperature to 28-34 °C. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a simple method for producing recombinant proteins including rHuPH20. It would have been obvious to further modify the teachings of EP3037529 to incorporate the recited culturing steps and/or conditions, and purify the produced PH20 using chromatography recited in the claims as routine experimentation and/or as desired for efficient production of the PH20. One of ordinary skill in the art at the time the invention was made would have a reasonable expectation of success because recombinantly producing PH20 is known in the art as shown by the above reference teachings. Hence, the claimed invention as a whole is prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
# Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of US Patent 12221638B2 (02/11/2025; PTO 892). Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
The claims and/or specification of the patents teach the claimed method for producing a recombinant protein, the method comprising: culturing host cells expressing the recombinant protein within a temperature range between 280C and 340C in a culture medium with a pH range between 6.8 and 7.2; during culturing the host cells, adjusting a glucose concentration in the culture medium to be within a range between 0.001 g/L and 4.5 g/L; and harvesting the recombinant protein from the culture medium when the produced recombinant protein shows a hyaluronidase enzymatic activity of 10,000 units/mL or higher.. Thus, the teachings anticipate the claimed invention.
# Claims 1-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of Application Serial No. 18940159. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
The claims and/or specification of the copending applications teach the claimed method for producing a recombinant protein, the method comprising: culturing host cells expressing the recombinant protein within a temperature range between 280C and 340C in a culture medium with a pH range between 6.8 and 7.2; during culturing the host cells, adjusting a glucose concentration in the culture medium to be within a range between 0.001 g/L and 4.5 g/L; and harvesting the recombinant protein from the culture medium when the produced recombinant protein shows a hyaluronidase enzymatic activity of 10,000 units/mL or higher.. Thus, the teachings anticipate the claimed invention.
Conclusion
#. No claim is allowed.
#. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christian L Fronda whose telephone number is (571)272 0929. The examiner can normally be reached Monday-Thursday and alternate Fridays between 9:00AM-5:00PM.
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/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652
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