DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Objections
Claim 20 is objected to because of the following informalities: In claim 20, the limitation “a cultivation vessel” in line 3 should read “the cultivation vessel” for consistency. Appropriate correction is required.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-8, 18-26 and 28 are rejected under 35 U.S.C. 103(a) as being unpatentable over Goldstein et al. (US 6,455,306; hereinafter “Goldstein”) in view of Borremans (already of record, WO 2008/145729 A1).
Regarding claim 1, Goldstein method for culturing mammalian cells, the method comprising culturing the mammalian cells (col. 9, ll. 4-46; col. 10, ll. 40-52; claim 1) in a device comprising a stirrer system (FIG. 2: agitator having a central shaft (216); col. 7, line 67 to col. 8, line 2) and a cultivation vessel (FIGS. 1 and 2: bioreactor (115,210); col. 10, ll. 40-52). Goldstein discloses wherein the stirrer system comprising at least three stirrer elements arranged above one another on the vertical stirrer shaft that effect thorough axial and radial mixing (FIG. 2: impellers 213; col. 8, ll. 12-19). Goldstein does not explicitly disclose wherein the stirrer system consists of two radially-conveying stirrer elements and one axially-conveying stirrer element arranged above one another on a vertical stirrer shaft, wherein the axially-conveying stirrer element is arranged above the two radially-conveying stirrer elements. Borremans discloses a stirrer system comprising a reaction tank and a stirrer system consisting of two radially-conveying stirrer elements and one axially-conveying stirrer element arranged above one another on the vertical stirrer shaft, wherein the axially-conveying stirrer element is arranged above the radially-conveying stirrer elements (see page 1, line 28 to page 2, line 21). Borremans discloses that such stirrer system facilitates good mixing in the liquid within the reactor by efficiently dispersing gas bubbles in the liquid within the reactor. In view of Borremans, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have employed the stirrer system of Borremans with the cultivation vessel of Goldstein for the purpose of facilitating good mixing of gases in the liquid within the reactor by efficiently dispersing gas bubbles in the liquid within the reactor, as suggested by Borremans (page 1, line 28 to page 2, line 21).
Regarding claim 2, modified Goldstein discloses all of the structural features of the claimed stirrer system and thus considered to have a Newton number of from 5.5 to 8.0 at a Reynolds number of from 5x104 to 5x105 when used in the cultivation vessel comprising cultivation medium (abstract, col. 10. 22-28 and 40-41).
Regarding claim 3, modified Goldstein discloses all of the structural features of the claimed stirrer system and thus considered to have, when used in the cultivation vessel comprising a cultivation medium (abstract, col. 10. 22-28 and 40-41) a mixing time ϴ.95 of about 10 seconds at a power input of about 0.3 W/kg.
Regarding claim 4, modified Goldstein further discloses wherein the stirrer system consists of two disk stirrers or two Rushton turbines as the radially-conveying stirrer elements (Rushton type stirrer including at least two blades on a disk; see, Borremans, page 14, ll. 35 to page 15, ll. 5), and one inclined-blade stirrer as the axially-conveying stirrer element (see, Borremans, page 8, ll. 24-25; page 9, ll. 21-35; page 14, ll. 35 to page 15, ll. 5).
Regarding claim 5, modified Goldstein discloses wherein the radially-conveying stirrer elements have between 2 and 8 stirrer blades (see, Borremans, page 14, ll. 35 to page 15, ll. 2), and the axially-conveying stirrer element has between 2 and 10 stirrer blades (see, Borremans, claims 1 and 5; page 15, ll. 3-5).
Regarding claim 6, modified Goldstein discloses wherein all the conveying stirrer elements have the same diameter d (see, Borremans, page 11, ll. 16-21).
Regarding claim 7, modified Goldstein discloses wherein the ratio of the diameter d of the stirring elements to the diameter D of the cultivation vessel is in the range of from 0.32 to 0.35 (see, Borremans, page 10, ll. 35 to page 11, ll. 11).
Regarding claim 8, modified Goldstein discloses wherein the pitch of the stirrer blades of the axially-conveying stirrer element is between 10° and 80° relative to the stirrer shaft (see, Borremans, page 8, ll. 24-26; page 9, ll. 33-35).
Regarding claim 18, Goldstein a device for culturing mammalian cells, comprising: a cultivation vessel (FIGS. 1 and 2: bioreactor (115,210); col. 10, ll. 40-52) and a stirrer system (FIG. 2: agitator having a central shaft (216); col. 7, line 67 to col. 8, line 2). Goldstein discloses wherein the stirrer system comprising at least three stirrer elements arranged above one another on the vertical stirrer shaft that effect thorough axial and radial mixing (FIG. 2: impellers 213; col. 8, ll. 12-19). Goldstein does not explicitly disclose wherein the stirrer system consists of two radially-conveying stirrer elements and one axially-conveying stirrer element arranged above one another on a vertical stirrer shaft, wherein the axially-conveying stirrer element is arranged above the two radially-conveying stirrer elements. Borremans discloses a stirrer system comprising a reaction tank and a stirrer system consisting of two radially-conveying stirrer elements and one axially-conveying stirrer element arranged above one another on the vertical stirrer shaft, wherein the axially-conveying stirrer element is arranged above the radially-conveying stirrer elements (see page 1, line 28 to page 2, line 21). Borremans discloses that such stirrer system facilitates good mixing in the liquid within the reactor by efficiently dispersing gas bubbles in the liquid within the reactor. In view of Borremans, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have employed the stirrer system of Borremans with the cultivation vessel of Goldstein for the purpose of facilitating good mixing of gases in the liquid within the reactor by efficiently dispersing gas bubbles in the liquid within the reactor, as suggested by Borremans (page 1, line 28 to page 2, line 21).
Regarding claim 19, modified Goldstein discloses a gas feed a (FIG. 2: port 242 is coupled to a sparging line 243 arranged adjacent the bottom of the cultivation tank; col. 8, ll. 46-50); and at least one inlet for adding one or more solutions (FIG. 2: ports (220,221); col. 8, lines 28-30). Modified Goldstein discloses wherein the gas feed of the cultivation vessel is arranged at the bottom of the cultivation tank (FIG. 2: port 242; col. 8, ll. 46-50). The claimed invention differs from the combination in that the gas feed is at the bottom of the cultivation vessel. However, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have rearranged the gas feed of Goldstein at the bottom of the cultivation vessel, since it has been held that a mere rearrangement of element without modification of the operation of the device involves only routine skill in the art (see also MPEP § 2144.04 VI. C.).
Regarding claim 20, modified Goldstein discloses all of the structural features of the claimed stirrer system and thus considered to have a Newton number of from 5.5 to 8.0 at a Reynolds number of from 5x104 to 5x105 when used in the cultivation vessel comprising cultivation medium (abstract, col. 10. 22-28 and 40-41).
Regarding claim 21, modified Goldstein discloses all of the structural features of the claimed stirrer system and thus considered to have, when used in the cultivation vessel comprising a cultivation medium (abstract, col. 10. 22-28 and 40-41) a mixing time ϴ.95 of about 20 seconds at a power input of about 0.05 W/kg and has a mixing time Ф 0.95 of about 10 seconds at a power input of about 0.3 W/kg when used in the cultivation vessel comprising cultivation medium.
Regarding claim 22, modified Goldstein further discloses wherein the stirrer system consists of two disk stirrers or two Rushton turbines as the radially-conveying stirrer elements (Rushton type stirrer including at least two blades on a disk; see, Borremans, page 14, ll. 35 to page 15, ll. 5), and one inclined-blade stirrer as the axially-conveying stirrer element (see, Borremans, page 8, ll. 24-25; page 9, ll. 21-35; page 14, ll. 35 to page 15, ll. 5).
Regarding claim 23, modified Goldstein discloses wherein the radially-conveying stirrer elements have between 2 and 8 stirrer blades (see, Borremans, page 14, ll. 35 to page 15, ll. 2), and the axially-conveying stirrer element has between 2 and 10 stirrer blades (see, Borremans, claims 1 and 5; page 15, ll. 3-5).
Regarding claim 24, modified Goldstein discloses wherein all the conveying stirrer elements have the same diameter d (see, Borremans, page 11, ll. 16-21).
Regarding claim 25, modified Goldstein discloses wherein the ratio of the diameter d of the stirring elements to the diameter D of the cultivation vessel is in the range of from 0.32 to 0.35 (see, Borremans, page 10, ll. 35 to page 11, ll. 11).
Regarding claim 26, modified Goldstein discloses wherein the pitch of the stirrer blades of the axially-conveying stirrer element is between 10° and 80° relative to the stirrer shaft (see, Borremans, page 8, ll. 24-26; page 9, ll. 33-35).
Regarding claim 28, Goldstein a device for culturing mammalian cells, comprising: a cultivation vessel comprising a mammalian cell culture medium and mammalian cells in the mammalian cell culture medium (FIGS. 1-2: bioreactor (115,210) containing mammalian cells and culture medium; Abstract, col. 10. 22-28 and 40-41); a vertical stirrer shaft along a middle axis of the cultivation vessel (FIG. 2: agitator having a central shaft 216; col. 7, line 67 to col. 8, line 2); a stirrer system consisting of two radially-conveying stirrer elements and one axially-conveying stirrer element arranged above one another on the vertical stirrer shaft, wherein the axially-conveying stirrer element is arranged above the radially-conveying stirrer elements; a gas feed (FIG. 2: port 242 is coupled to a sparging line 243 arranged adjacent the bottom of the cultivation tank; col. 8, ll. 46-50); and at least one inlet for adding one or more solutions (FIG. 2: ports 220,221; col. 8, lines 28-30). Goldstein further discloses a stirrer system comprising at least three stirrer elements arranged above one another on the vertical stirrer shaft that effect thorough axial and radial mixing (FIG. 2: impellers 213; col. 8, ll. 12-19). Goldstein does not explicitly disclose wherein the stirrer system consists of two radially-conveying stirrer elements and one axially-conveying stirrer element, wherein the axially-conveying stirrer element is arranged above the radially-conveying stirrer elements. Borremans discloses a stirrer system comprising a reaction tank and a stirrer system consisting of two radially-conveying stirrer elements and one axially-conveying stirrer element arranged above one another on the vertical stirrer shaft, wherein the axially-conveying stirrer element is arranged above the radially-conveying stirrer elements (see page 1, line 28 to page 2, line 21). Borremans discloses that such stirrer system facilitates good mixing in the liquid within the reactor by efficiently dispersing gas bubbles in the liquid within the reactor. In view of Borremans, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have employed the stirrer system of Borremans with the cultivation vessel of Goldstein for the purpose of facilitating good mixing of gases in the liquid within the reactor by efficiently dispersing gas bubbles in the liquid within the reactor, as suggested by Borremans (page 1, line 28 to page 2, line 21).
Goldstein discloses wherein the gas feed of the cultivation vessel is arranged at the bottom of the cultivation tank (FIG. 2: port 242; col. 8, ll. 46-50). The claimed invention differs from the combination in that the gas feed is at the bottom of the cultivation vessel. However, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have rearranged the gas feed of Goldstein at the bottom of the cultivation vessel, since it has been held that a mere rearrangement of element without modification of the operation of the device involves only routine skill in the art (see also MPEP § 2144.04 VI. C.).
Claim 9 is rejected under 35 U.S.C. 103(a) as being unpatentable over Goldstein et al. (already of record, US 6,455,306; hereinafter “Goldstein”) in view of Borremans (WO 2008/145729 A1) and Pla et al. (already of record, CA 2910619-A1; hereinafter “Pla”).
Regarding claim 9, Goldstein method for culturing mammalian cells, the method comprising culturing the mammalian cells (col. 9, ll. 4-46; col. 10, ll. 40-52; claim 1) in a device comprising a stirrer system (FIG. 2: agitator having a central shaft (216); col. 7, line 67 to col. 8, line 2) and a cultivation vessel (FIGS. 1 and 2: bioreactor (115,210); col. 10, ll. 40-52). Goldstein discloses wherein the stirrer system comprising at least three stirrer elements arranged above one another on the vertical stirrer shaft that effect thorough axial and radial mixing (FIG. 2: impellers 213; col. 8, ll. 12-19). Goldstein does not explicitly disclose wherein the stirrer system consists of two radially-conveying stirrer elements and one axially-conveying stirrer element arranged above one another on a vertical stirrer shaft, wherein the axially-conveying stirrer element is arranged above the two radially-conveying stirrer elements. Borremans discloses a stirrer system comprising a reaction tank and a stirrer system consisting of two radially-conveying stirrer elements and one axially-conveying stirrer element arranged above one another on the vertical stirrer shaft, wherein the axially-conveying stirrer element is arranged above the radially-conveying stirrer elements (see page 1, line 28 to page 2, line 21). Borremans discloses that such stirrer system facilitates good mixing in the liquid within the reactor by efficiently dispersing gas bubbles in the liquid within the reactor. In view of Borremans, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have employed the stirrer system of Borremans with the cultivation vessel of Goldstein for the purpose of facilitating good mixing of gases in the liquid within the reactor by efficiently dispersing gas bubbles in the liquid within the reactor, as suggested by Borremans (page 1, line 28 to page 2, line 21). Modified Goldstein does not explicitly disclose wherein the mammalian cells comprise a nucleic acid encoding the polypeptide. However, modified Goldstein does disclose wherein mammalian cells are cultured within the cultivation vessel (abstract, col. 10. 22-28 and 40-41). Pla discloses a device and method for culturing mammalian cells in a cultivation vessel for producing desired culture product (page 15, last full paragraph; page 27, fourth full paragraph). Pla further discloses wherein the cells can be mammalian cells comprising a nucleic acid encoding a recombinant protein (abstract, page 15, last full paragraph). In view of Pla, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have substituted the cells in the cultivation vessel of modified Goldstein with the cells as disclosed by Pla. One of ordinary skill in the art would have made said modification for the purpose of producing desired culture product as disclosed by Pla (page 15, last full paragraph). Further, one of ordinary skill in the art would have made said modification because said modification would have been the simple substitution of one known cells for another for the predictable result of culturing cells to produce desired cell culture.
Claim 27 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Goldstein in view of Borremans as applied to claim 18 above, and further in view of Kearns et al. (already of record, US 5,286,646).
Regarding claim 27, modified Goldstein discloses the device according to claim 18. Modified Goldstein does not explicitly disclose a dialysis module comprising a semi-permeable membrane located within the cultivation vessel to provide an exchange area between the mammalian cell culture medium in the cultivation vessel and a fresh mammalian cell culture medium. Kearns discloses a device capable of culturing mammalian cells. Kearns further discloses a dialysis module comprising a semi-permeable membrane located within a cultivation vessel. The semi-permeable membrane provides an exchange area between the mammalian cell culture medium in the cultivation vessel and a fresh mammalian cell culture medium (col. 6, ll. 14-19; col. 10, ll. 5-10). The semipermeable membrane is selected so that the cells and large molecules, such as proteinaceous materials, cannot pass through the membrane, but remain in the bioreactor (Abstract). Kearns further discloses an agitator with radially-conveying elements and axially-conveying elements with stirrer blades being used in conjunction with the dialysis module. In view of Kearns, it would have been obvious to a person of skill in the art at the time the invention was made to have employed the dialysis module disclosed by Kearns with the cultivation vessel of modified Goldstein in order to provide a simple and economic device for culturing cells which makes possible an increased cell density and consequently, an increased product yield (see, Kearns, col. 3 lines 55-60).
Conclusion
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/LIBAN M HASSAN/Primary Examiner, Art Unit 1799
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