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 .
Notes
All the objections and rejections in the previous Office Action not reiterated herein have been withdrawn.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: “at least one cell harvest system” in claim 17; and “at least one harvest module” in claim 19.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim(s) 10 is/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Amended dependent claim 10 recites the limitation "at least one flow controller for controlling a flow rate and direction of fluid material transferred into each of said plurality of 3-D culture vessels," however, said limitation fails to comply with written description requirement. The instant specification, as originally filed, discloses wherein the apparatus further comprises means such as meters, external computer and/or other means for controlling a flow rate of medium transferred into, and/or out of, each of the culture vessels (see, e.g., paragraph [0045]). However, there is nothing of record in the originally filed specification which states/suggests the apparatus comprises a controller that controls flow rate and direction of fluid material transferred into each of the culture vessels, as claimed. The specification is silent as to the structure that comprise the “flow controller” that performs the recited function of “for controlling a flow rate and direction of fluid material transferred into each of said plurality of 3-D culture.” Further, the specification is silent as to how the flow rate and direction is controlled. For support, Applicant cites paragraph [0040] of the instant specification. However, there is nothing in the cited paragraph that describes a flow controller that controls flow rate and direction of materials. As such, said limitation fails to comply with the written description requirement.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2, 4, 6, 10 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Merchav et al. (US 2005/0176143; hereinafter “Merchav”) in view of Ma (US 6,875,605) and Mohr et al. (DE 19801763-A1; with English machine translation) (hereinafter “Mohr”).
Regarding claims 1 and 10, Merchav discloses a cell culture apparatus, comprising: (a) at least one central medium container, said at least one central medium container comprising at least one cell culture medium, wherein said at least one central medium container does not contain cells (FIG. 1: medium reservoir 1; [0051] and [0113]); and (b) a plurality of three-dimensional (3-D) culture vessels configured for growing cells, wherein each of said plurality of 3-D culture vessels comprises at least one cell carrier, wherein said at least one cell carrier comprises at least one three-dimensional (3-D) matrix (FIG. 1: culture vessels 20, each including a surface adapted to contain the at least one cell carrier; [0013], [0020], [0051], [0077], [0089] and [0112]); wherein said at least one central medium container is operably connected to said plurality of 3-D culture vessels via at least one medium conduit that directs said at least one cell culture medium from said at least one central medium container through said at least one 3-D matrix of said plurality of 3-D culture vessels in a parallel configuration (FIG. 1); and wherein said cell culture medium flows through each of said plurality of 3-D culture vessels downward with the gravitation force and upward against the gravitation force (the plurality of 3-D culture vessels of Merchav are structurally the same as the instant plurality of 3-D culture vessels and thus considered to be fully capable of flowing through each of said plurality of 3-D culture vessels downward with the gravitation force and upward against the gravitation force). Merchav discloses wherein a pump is coupled between the central medium container and the plurality of culture vessels (FIG. 1), but does not explicitly disclose wherein each of said plurality of 3-D culture vessels is connected to at least one circulation pump configured to direct the medium to flow bot upwards against gravity and downwards with gravity in each of said plurality of 3-D culture vessels. However, it would have been prima facie obvious to one having ordinary skill in the art to have duplicated the pump of Merchav such that each of the culture vessels is coupled to a pump, since it has been held that a mere duplication of working parts of a device involves only routine skill in the art (MPEP § 2144.04 VI. B.). One would have been motivated to have duplicated the pump of Merchav such that each of the culture vessels is coupled to a pump for the purpose of providing desired fluid flow profile in each of the culture vessels. Ma discloses a cell culture apparatus comprising a plurality of culture vessels (see, FIGS. 2 and 7). Ma further discloses wherein a pump can be coupled to the plurality of culture vessels (FIG. 7) or that each of the plurality of culture vessels can be coupled to a separate pump (FIG. 2). In view of Ma, it would have been prima facie obvious to one of ordinary skill in the art to have modified the cell culture apparatus of Merchav with the cell culture apparatus of Ma such that such that each of the culture vessels is coupled to a separate pump. One of ordinary skill in the art would have made said modification for the purpose of providing desired fluid flow profile in each of the culture vessels separately. Modified Merchav does not explicitly disclose wherein the circulation pump is a bidirectional circulation pump, and at least one flow controller for controlling a flow rate and direction of fluid material transferred into each of said plurality of 3-D culture.
Mohr discloses a cell culture apparatus comprising a plurality of parallel culture vessel (see, e.g., FIGS. 3-7; [0035], [0051] and [0058] of the translation document), and a bidirectional circulation pump coupled to the parallel culture vessels ([0066], [0077]-[0080]). Mohr further discloses at least one flow controller for controlling a flow rate and direction of fluid material transferred into each of said plurality of culture vessels (control program; [0064] and [0077]-[0081]). In view of Mohr, it would have been prima facie obvious to one of ordinary skill in the art before the time of the effective filing date of the claimed invention to have employed the bidirectional circulation pump with flow controller of Mohr in place of circulation pump of Merchav to arrive at the claimed invention. One of ordinary skill in the art would have made said modification because said modification would have resulted in a pump having the added advantage of quickly reaching target level values ([0027]). Further, one of ordinary skill in the art would have made said modification because said modification would have been the substitution of one known circulation pump for another for the predictable result of conveying fluid through a system (see Mohr at [0050]).
Regarding claim 2, modified Merchav further discloses wherein at least one 3-D matrix is a fibrous synthetic matrix ([0039]).
Regarding claim 4, modified Merchav further discloses wherein said plurality of 3-D culture vessels further comprises at least one living cell ([0077], [0089] and [0112]).
Regarding claim 6, modified Merchav further discloses wherein said at least one central medium container comprises at least one means of monitoring and controlling the pH of said at least one cell culture medium (FIG. 1: pH probe inserted into the medium reservoir 1; [0051] and [0113]).
Regarding claim 12, modified Merchav further discloses wherein said at least one living cell is an adherent stromal cell that is derived from placenta, adipose tissue, bone marrow, or combinations thereof ([0012]-[0013] and [0072]).
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Merchav in view of Ma and Mohr as applied to claim 4 above, and further in view of Flendrig (US 6,372,495).
Regarding claim 5, modified Merchav discloses the cell culture apparatus according to claim 4. Modified Merchav does not explicitly disclose wherein said plurality of 3-D culture vessels are further operably connected to a means of measuring viability of said at least one living cell. Flendrig discloses that it is well-known in the art to employ means of measuring cell viability with cell culture vessels (bioreactors; col. 14, ll. 20-27). In view of Flendrig, it would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the means of measuring viability of living cells with the cell culture vessels of modified Merchav to arrive at the claimed invention. One of ordinary skill in the art would have made said modification since Flendrig discloses that it is well-known in the art to employ means of measuring cell viability with cell culture vessels (col. 14, ll. 20-27).
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Merchav in view of Ma and Mohr as applied to claim 1 above, and further in view of Guertin et al. (US 2012/0028234; hereinafter “Guertin”).
Regarding claim 8, modified Merchav discloses the cell culture apparatus according to claim 1. Modified Merchav further discloses wherein said at least one central medium container comprises at least one means of collecting data on a condition within said at least one central medium container (FIG. 1: pH probe inserted into the medium reservoir 1; [0051] and [0113]). Merchav does not explicitly disclose wherein said central medium container comprises a means of collecting data on conditions within said central medium container. Guertin discloses an apparatus comprising a plurality of culture vessels (FIG. 4: vessels 110a-b), each having a matrix therein ([0044] and [0054]), and a medium reservoir coupled to the plurality of culture vessels (FIG. 4: medium tank 118). Guertin further discloses wherein multiple sensors can be coupled to a medium tank (FIG. 4: 112a-b; [0057]-[0060] and [0087]). In view of Guertin, it would have been prima facie obvious to one of ordinary skill in the art to have employed the multiple sensors of Guertin with the medium reservoir of Merchav to arrive at the claimed invention. One of ordinary skill in the art would have made said modification for the purpose of maintaining the medium within the medium reservoir at the desired conditions and thereby provide optimum culturing environment for the cell culture within the culture vessels.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Merchav in view of Ma and Mohr as applied to claim 1 above, and further in view of Goodwin et al. (US 9,643,133; hereinafter “Goodwin”).
Regarding claim 15, modified Merchav discloses the cell culture apparatus according to claim 1. Modified Merchav does not explicitly disclose at least one heating blanket for each of said plurality of 3-D culture vessels so as to allow temperature control and insulation of each of said plurality of 3-D culture vessels. Goodwin discloses a cell culture apparatus comprising a culture vessel coupled to a heating jacket for regulating the temperature of the container (col. 3, ll. 30-37). In view of Goodwin, it would have been prima facie obvious to one of ordinary skill in the art to have employed the heating blanket of Goodwin with each of the plurality of 3-D culture vessels of modified Merchav for the purpose of maintaining the content within the plurality of 3-D culture vessels as the desired temperature.
Claim(s) 16 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Merchav in view of Ma and Mohr as applied to claim 1 above, and further in view of Altman et al. (US 2004/0219659; hereinafter “Altman”).
Regarding claim 16, modified Merchav discloses the cell culture apparatus according to claim 1. Modified Merchav does not explicitly disclose at least one flow diffuser configured to split said at least one cell culture medium entering from said at least one central medium container homogeneously within said plurality of 3-D culture vessels. Altman discloses a cell culture vessel comprising a flow diffuser (FIG. 1A: flow splitter adapted to split flow from an environment chamber into perfusion flow and a second flow). In view of Altman, it would have been prima facie obvious to one of ordinary skill in the art to have employed the flow diffuser of Altman with the apparatus of Merchav to arrive at the claimed invention. One of ordinary skill in the art would have made said modification for the purpose of introducing desired materials into the plurality of 3-D culture vessels simultaneously as suggested by Altman (FIG. 1A).
Regarding claim 20, modified Merchav does not explicitly disclose at least one flow disruptor configured to spread said at least one cell culture medium entering from said at least one central medium container homogeneously within said plurality of 3-D culture vessels.. Altman discloses a cell culture vessel comprising a flow diffuser (FIG. 1A: flow disruptor adapted to split flow from an environment chamber into perfusion flow and a second flow). In view of Altman, it would have been prima facie obvious to one of ordinary skill in the art to have employed the flow disruptor of Altman with the apparatus of Merchav to arrive at the claimed invention. One of ordinary skill in the art would have made said modification for the purpose of introducing desired materials into the plurality of 3-D culture vessels simultaneously as suggested by Altman (FIG. 1A).
Claim(s) 17-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Merchav in view of Ma and Mohr as applied to claim 1 above, and further in view of Conway et al. (WO 2016/113369-A1; hereinafter “Conway”).
Regarding claims 17 and 19, modified Merchav discloses the cell culture apparatus according to claim 1. Modified Merchav further discloses said at least one central medium container (FIG. 1: vessel 1), at least one harvest bag (cells are harvested and thus intrinsically includes harvest container; [0120], [0133]), and at least one harvest module for housing said plurality of 3-D culture vessel (i.e., an incubator for enclosing the cell culture apparatus (bioreactor system) of Merchav; see [0112] of Merchav). Modified Merchav does not explicitly disclose at least one cell harvest system comprising at least one tower (pump housing). Conway discloses a cell culture apparatus comprising a plurality of pumps and a tower for housing the plurality of pumps (FIG. 2). In view of Conway, it would have been obvious to one of ordinary skill in the art to have employed the tower of Conway with the cell culture apparatus of modified Merchav to arrive at the claimed invention. One of ordinary skill in the art would have made said modification for the purpose of protecting the pumps from the external environment. Further, one of ordinary skill in the art would have made said modification for east of transport of the pumps. Modified Merchav does not explicitly disclose at least one electrical cabinet. However, modified Merchav discloses wherein the cell culture apparatus includes controllers for automating the cell culture apparatus ([0048]). It would therefore have been prima facie obvious to one of ordinary skill in the art to have employed an electrical cabinet with the cell culture apparatus of modified Merchav for the purpose of protecting the electrical components of the controllers from the external environment. Further, one of ordinary skill in the art would have made said modification since such a component is well-known in the art to protect the electrical components of controllers from the environment.
Regarding claim 18, the limitations of the claim is directed to a manner of operating disclosed apparatus, it is noted that neither the manner of operating a disclosed device nor material or article worked upon further limit an apparatus claim. Said limitations do not differentiate apparatus claims from prior art. See MPEP § 2114 and 2115.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-2, 4-6, 8, 10, 12 and 15-20 have been considered but are moot in view of the new ground of rejection. The newly found reference of Mohr is relied upon for disclosing the claimed bidirectional circulation pump.
In response to the Applicant’s argument regarding claim 1 (see paragraph bridging pages 9 to 10 of the Remarks), Applicant’s argument is noted but it not persuasive. Nothing in Merchav that suggests the cells are discharged from the culture vessel into the circulation circuit. If the cells were to be discharged from the culture vessel into the circulation circuit of Merchav, such process would be detrimental to the cells being cultured as the circulation circuit comprises valves, pump and agitator. Further, nothing in Merchav that suggests that the circulating culture medium in the circulation circuit (even if it contains cells) are introduced into the central medium container that contains fresh media. The examiner would respectfully contend that contrary to the Applicant’s assertions, in Merchav, cells are not circulated in the circulation circuit because Merchav explicitly states that the cells are removed from the culture vessels after completing the cell culture process (see [0113]) which suggest that the cells do not exit the culture vessel into the circulation circuit.
In response to the Applicant’s argument regarding claim 1 (first full paragraph on page 10 of the Remarks), Applicant’s argument is noted but it is not persuasive. The instant specification defines the at least one cell carrier as a microcarriers such as alginate based carriers ([0020]). The microcarriers are packed inside the vessels and can include fibrous 3D carrier (]0020]). While the instant specification discloses that the microcarriers are arranged within the culture vessels, nothing in the instant specification that defines the microcarrier as having a separate structure for containing the 3-D matrix. The applied prior art discloses the structure of the claimed carrier comprising a 3-D matrix which is consistent with the definition disclosed by the instant specification.
In response to the Applicant’s argument regarding claim 1 (see paragraph bridging pages 10 to 11 of the Remarks), Applicant’s argument is noted but it not persuasive. Merchav explicitly discloses that the culture vessels are arranged parallel and that fluid media is circulated through the culture vessels.
In response to the Applicant’s argument regarding claim 1 (first full paragraph on page 11 of the Remarks), Applicant’s argument is noted but it is not persuasive. While the instant specification discloses pumps for controlling a flow rate of fluid material perfused into each of the vessels (Specification at [0056]), there is no explicit recitation in the instant specification that the pumps allow independent control of the flow rate in each of the plurality of 3-D culture vessel. Further, the instant pumps do not require special features that allow the pumps to perform the recited functions. Thus, the pumps recited in the claims are considered to be conventional pumps adapted for moving fluid through a system. Moreover, it is well-known in the art that conventional pumps are generally adapted to move fluids in the system at the desired rate. Therefore, each of the pumps of modified Ma can be set to move fluids in each of the vessels at desired rate which reads on independent control of flow rate by the pumps. As such, since the pumps disclosed by Ma are structurally the same as the instant pumps and thus considered to be capable of meeting the recited function of “allow independent control of the flow rate” as recited in independent claim 1.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LIBAN M HASSAN whose telephone number is (571)270-7636. The examiner can normally be reached on 8:30 AM - 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Marcheschi can be reached on 5712721374. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LIBAN M HASSAN/ Primary Examiner, Art Unit 1799
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