DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
1. Claims 1-30 have been cancelled. Claim 31 has been amended. Claims 32-50 are new.
Claims 31-50 are pending and under examination.
2. Upon further considerations, the rejection of claim 31 under 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn.
Double Patenting
3. 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 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 37, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web- based eTerminal Disclaimer may be filled out completely online using web- screens. An eTerminal Disclaimer that meets all requirements is auto- processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying- online/eterminal-disclaimer.
4. Claims 31-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 11,827,692. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same method for producing a recombinant protein by culturing CHO cells in a serum-free medium. The specific species of recombinant protein recited in the patent claims anticipates the genus recited in the instant claims. The instant specification discloses that: the bioreactor is inoculated with 0.5 x 106 to 3 x 106 cells/ml; perfusion could take place prior to the production phase; and a packed cell volume of less than or equal to 35% is achieved when using a VCD of 10x106-0.8x108 cells/ml during the production phase (i.e., between 10x106-1x108, as recites in the patent claims 1 and 11) (see p. 2, second and third paragraphs; p. 3, last paragraph; p. 4, lines 5-7; p. 9, first full and third paragraphs). The patent specification also discloses that a VCD of 10x106-0.8x108 cells/ml in the production phase results in a packed cell volume of less than or equal to 35% (see column 7, lines 40-50 and 55-60).
Thus, the instant claims and the patent claims are obvious variants.
5. Claims 31-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Patent No. 11,673,941. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same method for producing a recombinant protein by culturing CHO cells in a serum-free medium. The instant specification discloses that the bioreactor is inoculated with 0.5 x 106 to 3 x 106 cells/ml; and that perfusion could take place prior to the production phase (see p. 2, second and third paragraphs; p. 4, lines 5-7). While the patent claim 20 does not recite a packed cell volume, the patent specification discloses that a VCD of 10x106-80x106 cells/ml in the production phase results in a packed cell volume of less than or equal to 35% (see column 7, lines 40-50 and 55-61). While the patent claims do not recite purifying the recombinant proteins, one of skill in the art would have considered further purifying the recombinant protein as an obvious variant.
Thus, the instant claims and the patent claims are obvious variants.
6. Claims 31-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of U.S. Patent No. 11,634,476. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same method for producing a recombinant protein by culturing CHO cells in a serum-free medium comprising asparagine at a concentration of 5 mM or less. The instant specification discloses that the bioreactor is inoculated with 0.5 x 106 to 3 x 106 cells/ml; that perfusion could take place prior to the production phase and it can start at day 3; a VCD of 10x106-80x106 cells/ml during the production phase translates to less than or equal to 35% packed cell volume (see p. 2, second and third paragraphs; p. 3, last paragraph; p. 4, lines 5-7; p. 9, first full and third paragraphs). While the patent claim 24 does not recite a packed cell volume, the patent specification discloses that a VCD of 10x106-80x106 cells/ml (i.e., less 1x108) in the production phase results in a packed cell volume of less than or equal to 35% (see column 7, lines 40-50 and 55-61). While the patent claims do not recite purifying the recombinant protein, one of skill in the art would have considered further purifying the recombinant protein as an obvious variant.
Thus, the instant claims and the patent claims are obvious variants.
7. Claims 31-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,685,772. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same method for producing a recombinant protein by culturing CHO cells in a serum-free medium by using perfusion with a medium comprising asparagine at a concentration of 15 mM or less. The specific species of recombinant proteins recited in the patent claims anticipate the genus recited in the instant claims.
The instant specification discloses that the bioreactor is inoculated with 0.5 x 106 to 3 x 106 cells/ml; that perfusion could take place prior to the production phase and it can start at day 3; a VCD of 10x106-80x106 cells/ml during the production phase translates to less than or equal to 35% packed cell volume (see p. 2, second and third paragraphs; p. 3, last paragraph; p. 4, lines 5-7; p. 9, first full and third paragraphs).
While the patent claims 1, 11, and 21 do not recite a packed cell volume, the patent specification discloses that a VCD of 10x106-80x106 cells/ml (i.e., less 1x108) in the production phase results in a packed cell volume of less than or equal to 35% (see column 7, lines 40-50 and 55-61). The patent specification discloses that culture days 5-7 correlate to at least 10x106 viable cells/ml, i.e., perfusion starts when the viable cell density is at least 10x106 cells/ml, as required by the instant claims 36 and 46 (see Fig. 1-6A). While the patent claims do not recite purifying the recombinant proteins, one of skill in the art would have considered further purifying the recombinant proteins as an obvious variant.
Thus, the instant claims and the patent claims are obvious variants.
8. Claims 31-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 14-41 of U.S. Patent No. 11,292,829. Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same method for producing a recombinant protein/inducing growth arrest by culturing CHO cells in a serum-free medium by using perfusion with a medium comprising asparagine at a concentration of 15 mM or less. While the patent claims do not specifically teach producing a recombinant protein, one of skill in the art would have reasonably concluded that the CHO cells express a recombinant protein and that the production phase is for obtaining high yields of recombinant protein; one of skill in the art would have considered further purifying the recombinant protein as an obvious variant.
The instant specification discloses that the bioreactor is inoculated with 0.5 x 106 to 3 x 106 cells/ml; that perfusion could take place prior to the production phase and it can start at day 3; and a packed cell volume of less than or equal to 35% is achieved when the VCD during the production phase is 10x106-0.8x108 cells/ml (i.e., not more than 1x108 cell/ml, as required by the patent claim 1) (see p. 2, second and third paragraphs; p. 3, last paragraph; p. 4, lines 5-7; p. 9, first full and third paragraphs).
Thus, the instant claims and the patent claims are obvious variants.
Claim Rejections - 35 USC § 103
9. 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.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
10. Claims 31-50 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Etcheverry et al. (U.S 5,721,121), in view of all Marchant et al. (Mol. Biotechnol., 2008, 39: 69-77), Seewöster et al. (Biotechnol. Bioengin., 1997, 55: 793-797), and Douwenga et al. (Genetic Engineering & Biotechnology News, April 2010).
Etcheverry et al. teach a method for producing a recombinant protein from CHO cells cultured in a fed-batch bioreactor with a serum-free medium, the method comprising: (i) a growth phase, in which the CHO cells are expanded at 37⁰C; (ii) a transition phase entailing switching to production conditions by decreasing the temperature from 37⁰C to 30-35⁰C; and (iii) a production phase in which the CHO cells are cultured at 30-35⁰C (claims 31, 32, 38-42, and 48-50). Etcheverry et al. teach isolating and purifying the recombinant protein and formulating it into a pharmaceutical composition (claims 33, 34, 43, and 44) (see column 4, lines 5-19; column 10, lines 29-37; column 10, lines 56-64; column 14, lines 22-27; column 16, line 66 through column 17, line 24; Examples I and II; claims 1-8).
Etcheverry et al. do not teach using perfusion in the production phase (claims 31 and 41). However, using perfusion in the production phase is suggested by the prior art. For example, Marchant et al. teach that recombinant protein production per cell is increased if the CHO cells are maintained in the stationary phase at 32⁰C and that the recombinant protein yield could be increased if the stationary phase is maintained for a prolonged time (see p. 74, column 2, first full paragraph). Seewöster et al. teach that, when asparagine concentration in the culture medium reaches 10 µM, CHO cells enter the stationary phase, which can be maintained at this low concentration of asparagine (see paragraph bridging p. 794 and 795; p. 796, Fig. 3). Douwenga et al. teach that, in perfusion culture, fresh medium is continuously added, while the exhausted products are removed; while it allows for higher yields, perfusion culture generates large volumes of diluted product, which imposes significant challenges for downstream recovery and purification. Douwenga et al. teach that perfusion could be used in conjunction with fed-batch to produce a single concentrated batch at the end of the culture (see paragraphs 3-6). Based on the combined teachings pf Marchant et al., Seewöster et al., and Douwenga et al. one of skill in the art would have reasonably concluded that (1) maintaining the CHO cells of Etcheverry et al. in a prolonged stationary phase during the production phase would increase the recombinant protein yield; (2) a prolonged stationary phase could be achieved by maintaining the asparagine concentration at 10 µM; and (3) maintaining the asparagine concentration at 10 mM could be achieved by perfusion with a medium comprising 10 µM asparagine. One of skill in the art would have found obvious to modify Etcheverry et al. by perfusing CHO cells in the production phase with a medium comprising 10 µM (claims 37 and 47), with the reasonable expectation that doing so would enhance the recombinant protein yield by maintaining the CHO cells in a prolonged stationary production phase.
Furthermore, Etcheverry et al. teach that the packed cell volume (PCV) and viable cell density (VCD) are result-effective variables with respect to recombinant protein yield (see column 5, lines 1-8; Fig. 1). One of skill in the art would have found obvious to use routine experimentation and vary the VCD at the start of perfusion (i.e., also the day when perfusion is started and PCV), with the reasonable expectation that doing so would identify the optimal conditions for recombinant protein production (claims 31, 35, 36, 41, 45, and 46). Routine optimization is not considered inventive and no evidence has been presented that the selection the claimed ranges was other than routine or that the results should be considered unexpected in any way as compared to the closest prior art (see MPEP 2144.05 II).
Thus, the claimed invention was prima facie obvious at the time the invention was made.
11. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633
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