DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Response to Amendment
All the objections and rejections in the previous Office Action not reiterated herein have been withdrawn.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Applications No. 60/892,653; 60/943,351; 60/974,677, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claims 9 and 24 require wherein the sidewall of at least one of the microwells comprises an anti-adherence treatment. However, provisional Applications No. 60/892,653; 60/943,351; 60/974,677 do not provide adequate support for said limitations.
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.
Claims 9, 14, 17, 21-22, 24-26, 28 and 30 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.
Independent claim 9 recites the limitations "wherein the sidewall and base wall of at least one of the microwells comprises an anti-adherence treatment, and wherein at least one of the microwells comprises one or more cells that are adhered to neither the sidewall the base wall," however, said limitation fails to comply with written description requirement. The instant specification, as originally filed, discloses that, in some embodiments, an anti-adherent coating (such as pluronic acid)may be applied to sidewalls (120) (see paragraph [0115]). However, there is nothing of record in the originally filed specification which states/suggests the base wall is coated with anti-adherent coating, such that cells do not adhere to the base wall. As such, said limitations constitute new matter.
Claims 14, 17, 21-22, 25-26, 28 and 30 are rejected by virtue of their dependence upon a rejected base claim.
Independent claim 24 recites the limitations "wherein the sidewall and base wall of at least one of the microwells comprises an anti-adherence treatment, and wherein at least one of the microwells comprises one or more cells that are not adhered to the sidewall and the base wall," however, said limitation fails to comply with written description requirement.
The instant specification, as originally filed, discloses a that, in some embodiments, an anti-adherent coating (such as pluronic acid)may be applied to sidewalls (120) (see paragraph [0115]). However, there is nothing of record in the originally filed specification which states/suggests the base wall is coated with anti-adherent coating, such that cells do not adhere to the base wall. As such, said limitations constitute new matter.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 29-30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “substantially” in claims 29-30 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how uniform the cell aggregate needs to be meet the claimed size.
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 4, 8, 10, 13, 15-16, 27 and 30 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Ravkin et al. (US 2006/0013031; “Ravkin”) in view of Sakamoto (US 2005/0106074), Duffy et al. (US 2005/000974; “Duffy”) and Wikswo et al. (US 2006/0099705; hereinafter “Wikswo”).
Regarding claims 4, 8 and 10, Ravkin discloses a plastic microwell cell culture device ([0048]) comprising: a) a body comprising an upper region defining an upper plane (FIGS. 6A-6C; [0095]-[0097]); b) a plurality of distinct wells extending downwardly from the upper plane into the body, each of the plurality of wells comprising an array of microwells in a closed bottom wall thereof (a plurality of wells (134) comprising an array of sub-wells (136); see [0095]-[0097]; see FIGS. 6B-6C); c) each of the microwells comprising an axis extending perpendicularly to the upper plane (FIGS. 5 and 6C); and d) each of the microwells comprising a sidewall (FIGS. 6B-C: frustoconical sub-wells; [0097]), wherein the microwells are defined by a width (e.g., width measured along the floor or opening of the sub-wells; see FIG. 6C), and a distance between two adjacent microwells along a bottom wall upper plane (FIG. 6: 142), and wherein the at least one of the microwells comprises one or more cells that are not adhered to the sidewall (i.e., cells adhere to the bottom of the microwells and optionally not the sidewall; [0034], [0074]). Ravkin discloses wherein each of the microwells comprises a sidewall (FIGS. 6B-C: frustoconical sub-wells; [0097]), but does not explicitly disclose wherein the sidewall of at least one of the microwells comprises four wall components that form an inverted pyramid and extend inwardly towards the axis. However, Ravkin does disclose wherein the microwells can be any desired shape and size ([0042]). Sakamoto discloses a microwell cell culture device comprising a plurality of microwells (FIG. 1: plate (1); [0058]), each of the wells can have various shapes including an inverted pyramid having four wall components (FIGS. 4A-4D; [0059]). In view of Sakamoto, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have modified the shape of the microwells of Ravkin to have inverted pyramid shape as disclosed by Sakamoto ([0059]). One of ordinary skill in the art would have made said modification since Ravkin discloses that the microwells can have desired shape and size ([0042]). Modified Ravkin does not explicitly disclose wherein the four wall components are at an angle between 20° to 80° with respect to the upper plane. Duffy discloses a device comprising a plurality of wells (FIG. 3). Each of the wells can have an inverted truncated pyramid ([0116]). Duffy further discloses that the angle can be adjusted as desired for a particular application ([0116]). In view of Duffy, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have modified the microwells of modified Ravkin to have the claimed angle to arrive at the claimed invention. One of ordinary skill in the art would have made said modification because Duffy discloses that the angle of the walls can be adjusted as desired for particular application ([0116]). Furthermore, it’s noted that the courts have held where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device (In Gardner v. TEC Systems, Inc., 725 F.2d 1338, 220 USPQ 777). See MPEP 2144.04 IV. A.
Modified Ravkin discloses wherein the microwells are defined by a width (e.g., width measured along the floor or opening of the sub-wells; see FIG. 6C), and two adjacent microwells are spaced apart by a distance (see FIGS. 6A-6C). Modified Ravkin does not explicitly disclose wherein the microwells are defined by a width of less than 1 millimeter, and a distance between any two adjacent microwells along the bottom wall is less than the width and less than 100 microns. However, in another embodiments, modified Ravkin does disclose that the microwells can have any desired shape, size and spacing between the microwells ([0042]-[0043]). For example, a spacing between two adjacent microwells (apertures or sub-wells) can be less than a width of the microwells (a width of less than 1 millimeter; see [0038]-[0051]-[0054]). It would therefore have been prima facie obvious to one of ordinary skill in the art at the time of the invention to have modified the width and spacing between adjacent microwells of modified Ravkin to arrive at the claimed invention. One of ordinary skill in the art would have made said modification for the purpose of maximizing sample capacity and minimize sample cross-contamination as disclosed by modified Ravkin ([0052]). Further, one of ordinary skill in the art would have made said modification because said modification would have been a matter of an engineering design choice which a person of ordinary skill in the art would have found obvious since the claimed device would not perform differently than the prior art device of modified Ravkin. Modified Ravkin discloses wherein each of the microwells comprises an adherent cells ([0034]), but does not explicitly disclose wherein the sidewall comprises an anti-adherence treatment such that cells do not adhere to the sidewall. However, modified Ravkin does disclose wherein the adherent cells can be allowed to adhere to the sidewall, the bottom of the microwells, or both ([0034], [0074]). Wikswo discloses a bioreactor comprising a substrate having a plurality of array of chambers (FIG. 1A: 204; [0076]), each comprising a plurality of chambers (see, e.g., FIGS. 1A-1B: chambers 206; [0076]). Wikswo further discloses wherein sidewalls of the plurality of chambers can be coated with materials that inhibit or enhance cell adhesion (Wikswo at [0080]-[0081]). In view of Wikswo, it would have been prima facie obvious to one of ordinary skill in the art to have employed the anti-adherent treatment of Wikswo to the sidewall of the microwells of modified Ravkin to prevent the adherent cells to attach to the sidewall when not desired (i.e., when adherence cells attachment to the bottom of the microwells is desired; [0074]). Furthermore, it’s noted that the courts have held where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device (In Gardner v. TEC Systems, Inc., 725 F.2d 1338, 220 USPQ 777). See MPEP 2144.04 IV. A.
Regarding claim 13, modified Ravkin further discloses wherein the distance is less than 10 microns (e.g., 25% of a sub-well having a diameter 20 microns; see [0054] of Ravkin).
Regarding claims 15-16, modified Ravkin further discloses wherein the wells have a dimension (width) at the upper plane (see, e.g., Ravkin at FIG. 6c), but does not explicitly disclose wherein the wells have the claimed dimension. However, Modified Ravkin further discloses that the wells can have any suitable size and shape ([0041]). It would therefore have been prima facie obvious to one of ordinary skill in the art to have modified the dimensions of the wells of modified Ravkin to comprise the claimed dimension since Ravkin discloses that the wells can be any suitable size and shape (Ravkin at [0041]). Moreover, it’s noted that the courts have held where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device (In Gardner v. TEC Systems, Inc., 725 F.2d 1338, 220 USPQ 777). See MPEP 2144.04 IV. A.
Regarding claim 27, modified Ravkin further discloses that each microwell comprises a plurality of cells ([0034], [0074], [0083]), but does not explicitly disclose wherein the one or more cells are aggregate of plurality of cells. However, it would have been prima facie obvious to one of ordinary skill in the art to have substituted the one or more cells in the microwells of the device of modified Ravkin with the claimed cells to arrive at the claimed invention. One of ordinary skill in the art would have made said modification for the purpose of assaying cell aggregate. 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 type of cells with another.
Regarding claim 29, modified Ravkin further discloses that each microwell comprises a plurality of cells ([0034], [0074], [0083]), but does not explicitly disclose wherein the one or more cells are aggregate of a plurality of cells, and each aggregate is substantially uniform in size. However, it would have been prima facie obvious to one of ordinary skill in the art to have substituted the one or more cells in the microwells of the device of modified Ravkin with the claimed cells to arrive at the claimed invention. One of ordinary skill in the art would have made said modification for the purpose of assaying cell aggregates. 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 type of cells with another.
Response to Arguments
Applicant’s arguments with respect to claim(s) 4, 8-10, 13-17, 21-22 and 24-30 have been considered but are moot in view of the new ground of rejection.
In response to the Applicant’s argument regarding the term “substantially” recited in claims 29-30 (see Remarks/Arguments at pages 5 to 6), Applicant’s argument is not persuasive. The term “substantially” in claims 29-30 is a relative term which renders the claim indefinite. It is unclear how uniform the cell aggregate needs to be to meet the claimed aggregate size. It is unclear the degree of uniformity that is required for the cell aggregate to be considered “substantially uniform. ”Thus, the scope of said limitation is unclear.
In response to the Applicant’s argument that modifying Ravkin to comprise an inverted pyramidal microwells would frustrate the purpose of Ravkin (see Remarks/Arguments at pages 6 to 7), Applicant’s argument is not persuasive. Nothing in Ravkin that precludes from employing microwells having an inverted pyramid shape. In fact, Ravkin explicitly states that the microwells can be varies shapes and sizes including frustoconical wells. Further, as discussed in the rejection, the newly found prior art (Sakamoto) discloses that cell culture microwells can be have various shapes including wells having frustoconical and inverted pyramid shapes. As to the Applicant’s argument regarding the formation of cell aggregates within the microwells, as discussed in the rejection, the combination of Ravkin and Sakamoto discloses the claimed microwells having the claimed shape. Thus, the combination is considered to be capable of forming desired cells within the microwells included cell aggregates. In response to applicant's argument that the device disclosed by Ravkin is inoperable for the purpose of producing uniformly-sized cell aggregates, due to frustoconical sub-wells intended for adherent cell culture, a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In this case, the applied prior art disclose all of the structural features of the claimed microwells and thus fully capable of producing cell aggregates. In response to the Applicant’s argument that Duffy is silent regarding microwells within wells (Remarks/Arguments at page 7), Applicant’s argument is not persuasive. Ravkin is the primary reference and disclosed the claimed device having microwells within wells. As discussed in the revised rejection above, Duffy is relied upon for disclosing the claimed angle and not the shape of microwells. Duffy is a pertinent art because Duffy discloses that the tapering of the sidewalls of the wells in which cells are disposed can be varied. Duffy does not need to disclose microwells within wells as such feature is disclosed by the primary reference. In response to the Applicant’s argument regarding the reference of Wikswo (Remarks/Arguments at page 7), Wikswo is relied upon for disclosing that sidewalls of the plurality of chambers containing cells can be coated with materials that inhibit or enhance cell adhesion. Wikswo is pertinent art because, similar to Ravkin, discloses culturing cells in plurality of chambers (wells). In response to applicant's argument that the combination of Ravkin, Duffy and Wikswo fails to teach or suggest a device that advantageously produces a plurality of uniformly-sized cell aggregates (Remarks/Arguments at page 9), a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In this case, the applied prior art disclose all of the structural features of the claimed microwells and thus fully capable of producing cell aggregates. In this case, the applied prior art disclose all of the structural features of the claimed microwells and thus fully capable of producing cell aggregates.
Conclusion
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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/LIBAN M HASSAN/Primary Examiner, Art Unit 1799