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 .
Claims 6-13, 15-26, 28, 29, 31-36 have been canceled. Claims 1-5, 14, 27, 30 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-5, 14, 17-16, 18, in the reply filed on 2-19-25 is acknowledged.
Claims 27, 30 have been withdrawn.
Claims 1-5, 14 remain under consideration.
Applicant's arguments filed 2-18-26 have been fully considered but they are not persuasive.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112
Written Description
Claims 1-5, 14 remain 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.
A) The specification does not provide written description for introducing mammalian pluripotent cells into a microfluidic device and contacting the cells with any basal medium comprising FGF2, BMP4 in any 1st cell channel comprising a 1st loading reservoir and a 2nd cell channel comprising a 2nd loading reservoir in “fluid communication with” a “3rd channel compris[ing] gel matrix” to obtain an “embryonic sac” as broadly encompassed by claim 1 other than introducing mammalian pluripotent cells into a microfluidic device, contacting the cells with amniotic differentiation medium such that amniotic cells are obtained.
Claim 1 is drawn to “A method for preparing an embryonic sac, comprising: a) introducing mammalian pluripotent stem cells into a microfluidic device comprising parallel first, second, and third channels wherein the first channel is a cell channel comprising a first loading reservoir and said second channel are isa cell channel channels comprising a second loading reservoir, wherein the first and second channels are operably linked to the in fluid communication with said third channel, wherein the third channel comprises a gel matrix, wherein said mammalian pluripotent stem cells are introduced to said said [sic] first channel or said second channel of said microfluidic device via said first or second loading reservoir; and b) introducing a first medium comprising basal medium comprising FGF2 plus BMP4 into said first channel and introducing a second medium comprising basal medium comprising FGF2 into said cell loading second channel for a defined period of time to generate said embryonic sac, wherein said embryonic sac comprises a single layer of amniotic ectoderm cells that express TFAP2A at a first pole of said sac exposed to BMP4 and a stratified, epiblast epithelium comprising epithelial cells that express CDX2 and T at a second pole exposed to basal medium.”
The claim encompasses obtaining any “embryonic sac” which encompasses any combination of cells because an embryo sac contains totipotent cells, pluripotent cells, amniotic tissue, umbilical cord tissue, mesoderm, endoderm, ectoderm, mesenchymal cells, retinal, epidermal, mucosal, cardiac, muscle, liver, pancreas, adipose, gonadal, and neural cells depending upon the stage of the embryo. Applicants elected obtaining “posterior embryo-like” tissue, but the metes and bounds of such tissue cannot be determined (see 112/2nd).
The examples are limited to introducing mammalian pluripotent cells (pg 18, line 32) into channels of a microfluidic device, contacting the cells with media capable of maintaining pluripotency (e.g. serum-free mTeSR or TeSR-E8; pg 19, lines 8-14), and adding exogenous Wnt, activin, and/ or BMP4 (amniotic differentiation medium) such that “posterior” embryo tissue is obtained (pg 20, lines 21-30).
Pg 26, line 18, describes a “single layer of ectoderm-like cells at a pole exposed to BMP4, and a stratified, epiblast-like epithelium at the other pole”; however, the metes and bounds of “ectoderm-like cells”, “epiblast-like epithelium”, pre-posterior streak-like cells, when “epiblast-like epithelium” is stratified or comprises pre-posterior streak-like cells at pole” cannot be determined. The specification does not teach the “epiblast-like” cells have “pre-posterior streak-like cells” at a pole exposed to basal medium. The “single” and “stratified” layers were not obtained after putting pluripotent cells into a microfluidic device with basal media containing FGF2, and BMP4 in a “1st channel” and basal medium and FGF2 in a “2nd channel” as required in claim 1.
The specification does not teach obtaining an “embryonic sac compris[ing] a single layer of amniotic ectoderm cells that express TFAP2A at a first pole” and an “epiblast epithelium comprising epithelial cells that express CDX2 and T at a second pole exposed to basal medium” as required in claim 1. The specification does not teach the structures/functions of amniotic ectoderm cells or epiblast-like epithelium obtained in the examples. The specification does not correlate the structures/functions of amniotic ectoderm-like cells or epiblast-like epithelium obtained in the examples to a single layer of “amniotic ectoderm cells that express TFAP2A” and “a stratified epiblast epithelium [that expresses] CDX2 and T” as required in claim 1. The specification does not correlate obtaining amniotic ectoderm-like cells or epiblast-like epithelium obtained in the examples to obtaining any “embryonic sac” tissue, specifically and “embryonic sac” that contains totipotent cells, pluripotent cells, amniotic tissue, umbilical cord tissue, mesoderm, endoderm, ectoderm, mesenchymal cells, retinal, epidermal, mucosal, cardiac, muscle, liver, pancreas, adipose, gonadal, and neural cells as broadly encompassed by claim 1. At best, the amniotic ectoderm-like cells or epiblast-like epithelium obtained in the examples appear to be “amniotic tissue”. Accordingly, the specification lacks written description for obtaining an “embryonic sac compris[ing] a single layer of amniotic ectoderm cells that express TFAP2A at a first pole” and an “epiblast epithelium comprising epithelial cells that express CDX2 and T at a second pole exposed to basal medium” as required in claim 1.
Response to arguments
Applicants point to Fig. 14 and pg 14 for support. Applicants’ argument is not persuasive. Fig. 14 is limited to a device with three channels. The 1st channel is connected to the 3rd channel by holes; the 2nd channel is connected to the 3rd channel by holes;.the 1st and 2nd channels are not touching; the 3rd channel contains gel matrix. These features are not in claim 1. Fig. 14 and pg 14 do not teach obtaining an embryonic sac having 1st and 2nd poles and the cellular features of claim 1.
B) While microfluidic devices were known in the art, the wording of the “a microfluidic device comprising parallel first, second, and third channels wherein the first channel is a cell channel comprising a first loading reservoir and said second channel are isa cell channel channels comprising a second loading reservoir, wherein the first and second channels are operably linked to the in fluid communication with said third channel, wherein the third channel comprises a gel matrix, wherein said mammalian pluripotent stem cells are introduced to said said [sic] first channel or said second channel of said microfluidic device via said first or second loading reservoir” does not make sense in context of differentiating pluripotent cells into amniotic tissue. The claim appears to encompass two cell culture channels and a third channel comprising gel matrix that is operably linked to the 1st and 2nd channels.
The specification is limited to using the microfluidic device in Fu WO 2018/106997 (pg 14, line 26; et al.). The microfluidic device of Fu is limited to:
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in which “cells are generated in a device comprising parallel first, second, and third channels wherein the first channel 1 and second channel 2 are cell channels comprising a loading reservoir 4 operably linked to the third channel 3 comprising a gel matrix. Exemplary devices are shown in Figure 14. As shown in Fig 14, the cell culture channel 1 (e.g., first channel) is in fluid communication with the cell induction channel 2 (e.g., second channel) via the gel channel (third channel) 3” (pg 14, lines 27-33). However, the description of what goes in what channels and how the components in each channel “communicate” cannot be determined. Fu WO 2018/106997 refers to the microfluidic device of Zheng (Adv. Healthcare Materials, 2016, Vol. 5, pg 1014-1024) in Example 3 as the microfluidic device. However, Zheng is limited to:
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It is unclear how the cell culture channel, a gel channel, a cell induction channel, and a cell loading channel in the channels in Fu or Zheng correlate to the 1st and 2nd cell channels and the 3rd gel matrix channel claimed. The specification does not correlate the limited teachings of 3 channels with specific purposes described by Zheng to the two “cell channels” and one “gel matrix” channel in claim 1. The claim encompasses channels that do not have holes in them. The claim encompasses two cell growth channels but no cell “induction channel”. However, the specification does not correlate the communication, i.e. holes between channels (?), described by Zheng to channels without holes or without a matrix in the middle as broadly encompassed by claim 1.
Claim 1 requires “introducing [ ] basal medium comprising FGF2 plus BMP4 into said channel and introducing basal medium comprising FGF2 into the second channel” and introducing mammalian pluripotent cells into the first or second channel. However, the specification does not provide adequate guidance regarding how to use the device described by Zheng or any other microfluidic device to obtain an “embryonic sac compris[ing] a single layer of amniotic ectoderm cells that express TFAP2A at a first pole” and an “epiblast epithelium comprising epithelial cells that express CDX2 and T at a second pole exposed to basal medium” as required in claim 1. The specification fails to provide adequate guidance for what to do after putting pluripotent cells into the 1st channel comprising basal medium containing FGF2 and BMP4 or the 2nd channel comprising basal medium and FGF2 to obtain the “embryonic sac” having the structure claimed. The specification fails to provide adequate guidance regarding the specific gel, the flow techniques, the “fluid communication”, and differentiation protocols required to obtain after putting the pluripotent cells into the device. For example, claim 4 says additional components are added to the basal medium after a period of time, but the specification does not teach which additional component are required or when they must be added to obtain an “amniotic sac” having the structure set forth in claim 1. Claim 14 requires there are “posts” and “gel matrix” in the 3rd chamber and cells are cultured “in pockets between said posts and said gel matrix”; however, the cells are only added to the 1st or 2nd channel, so it is unclear how/when the cells move to the 3rd channel or how they form “pockets” in between “posts” and “gel matrix”. The specification fails to provide adequate of how to apply those limited teachings of Zheng to other microfluidic devices will be required. Therefore, it is unclear how to use the device of Zheng or any other device to obtain the “amniotic sac” in claim 1.
Response to arguments
Applicants point to Fig. 14 and pg 14 for support. Applicants’ argument is not persuasive. Fig. 14 is limited to a device with three channels. The 1st and 2nd channels are connected to the 3rd channel by holes; the 1st and 2nd channels are not touching. These features are not in claim 1. The specification does not provide adequate guidance regarding the specific gel, the flow techniques, the “fluid communication”, and differentiation protocols required to obtain after putting the pluripotent cells into the device to obtain an embryonic sac having 1st and 2nd poles and the cellular features of claim 1.
Indefiniteness
Claims 1-5, 14 remain 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.
A) The metes and bounds of an “embryonic sac compris[ing] a single layer of amniotic ectoderm cells that express TFAP2A at a first pole” and an “epiblast epithelium comprising epithelial cells that express CDX2 and T at a second pole exposed to basal medium” in claim 1 cannot be determined.
Applicants use the phrase “posteriorized embryonic-like sac” on pg 4, line 8; pg 6, line 1 and 9; pg 7, line 5; pg 7, line 1; pg 10, line 32; pg 15, line 17; and pg 27, line 2 without defining the metes and bounds of the phrase.
Pg 11, lines 27-32, states “‘embryo-like tissue’ refers to tissue differentiated in vitro (e.g., from a stem cell) that has one or more properties of an embryo (e.g. one or more of primordial germ cell-like cells, amniotic ectoderm-like cells, and an epiblast-like epithelium). However, embryo-like tissue lacks all properties of an embryo and is generally unable to develop beyond the embryo stage. In some embodiments, embryo-like tissue lacks a primitive endoderm and/or trophoblast.” However, this is not a definition because it does not provide the metes and bounds of the phrase. Pg 11, lines 27-32, merely discuss examples of “embryo-like tissue” without defining the metes and bounds of the phrase. It is unclear whether tissue having any feature mentioned, e.g. tissue obtained from any stem cell, as broadly encompassed by “tissue differentiated in vitro (e.g. from a stem cell) that has one or more properties of an embryo” such as cells with nuclei that proliferate and differentiate.
The metes and bounds of “PGC-like cells”, amniotic ectoderm-like cells” and “epiblast-like epithelium” within the discussion on pg 11 are also unclear because the terms are not defined. This discussion may guide and hint at what is encompassed by the phrase, but it does not define the phrase.
The metes and bounds of the elected posteriorized “embryonic sac” tissue is indefinite because it is unclear how the position or location of the tissue within the embryo defines the structure/function of the tissue. Depending upon the stage of the embryo, the “posterior” of an embryo may contain totipotent cells, pluripotent cells, amniotic tissue, umbilical cord tissue, mesoderm, endoderm, ectoderm, mesenchymal cells, retinal, epidermal, mucosal, cardiac, muscle, liver, pancreas, adipose, gonadal, and neural cells. So it is unclear what structures/functions are encompassed by the concept of “posterior “embryo tissue. For example, it is unclear whether anterior embryo tissue can be “like” posterior embryo tissue because it is unclear how the location of the tissue distinguishes the tissues when the have the same structure/function. In another example, it is unclear whether any ectoderm stem cell found in a newborn is encompassed by the claim because it is like ectoderm stem cells found in the posterior (or anterior) of an embryo.
The art at the time of filing did not define the metes and bounds of posteriorized “embryonic sac” tissue.
It is unclear when tissue is “posteriorized” or “posteriorized embryo sac” as elected.
It is unclear when embryo tissue, specifically posterior embryo tissue, is a “sac”.
The art at the time of filing did not define the metes and bounds of posteriorized “embryonic sac” tissue as elected.
Therefore, those of skill would not be able to determine the line at which a tissue was/was not an posteriorized “embryonic sac” tissue as required in claim 1 and elected because the metes and bounds of the phrase cannot be determined.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
B) The metes and bounds of the structures of the microfluidic device in claim 1 cannot be determined. The wording of the “a microfluidic device comprising parallel first, second, and third channels wherein the first channel is a cell channel comprising a first loading reservoir and said second channel are isa cell channel channels comprising a second loading reservoir, wherein the first and second channels are operably linked to the in fluid communication with said third channel, wherein the third channel comprises a gel matrix, wherein said mammalian pluripotent stem cells are introduced to said said [sic] first channel or said second channel of said microfluidic device via said first or second loading reservoir” does not make sense in context of differentiating pluripotent cells into “embryonic sac” tissue.
The specification is limited to using the microfluidic device in Fu WO 2018/106997 (pg 14, line 26; et al.). The microfluidic device of Fu is limited to:
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in which “cells are generated in a device comprising parallel first, second, and third channels wherein the first channel 1 and second channel 2 are cell channels comprising a loading reservoir 4 operably linked to the third channel 3 comprising a gel matrix. Exemplary devices are shown in Figure 14. As shown in Fig 14, the cell culture channel 1 (e.g., first channel) is in fluid communication with the cell induction channel 2 (e.g., second channel) via the gel channel (third channel) 3” (pg 14, lines 27-33). However, the description of what goes in what channels and how the components in each channel “communicate” cannot be determined. Fu WO 2018/106997 refers to the microfluidic device of Zheng (Adv. Healthcare Materials, 2016, Vol. 5, pg 1014-1024) in Example 3 as the microfluidic device. However, Zheng is limited to:
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It is unclear how the 1st and 2nd cell culture channels and 3rd gel channel in claim 1 correlate to any of the channels in Fu or Zheng. The specification does not correlate the limited teachings of 3 channels with specific purposes described by Zheng to the breadth of channels and configurations in claim 1. The claim encompasses channels that do not have holes in them or are in “fluid communication”. However, the specification does not correlate the “fluid communication”, i.e. holes between channels (?), described by Zheng to channels without holes that are in are in “fluid communication” as broadly encompassed by claim 1.
Claim 1 never requires the mammalian pluripotent cells touch the basal media containing FGF and MBP4 or the basal medium containing FGF2 because the media may push the cells out of the 1st or 2nd channel into another channel.
It is unclear how the 1st and 2nd cell channels are structurally different (if at all) or how they are used to create polarized embryonic sac tissue with cells that express TFAP2A on one pole and cells that express CDX2 and T on the other.
All of these factors make the structure of the microfluidic device and the channels indefinite.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
C) The metes and bounds of the structures of the microfluidic device in claim 14 cannot be determined. The structure of the 3rd channel containing “posts” and “gel matrix” with stem cells “cultured in pockets between said posts and said gel matrix” cannot be envisioned. The cells are introduced into the 1st or 2nd “channel” containing basal media containing FGF2 and BMP4 or FGF2, but claim 14 never requires the cells contact the culture media or that the cells and media are introduced into the same channel or that the “posts” in claim 14 are something other than the channels in claim 1.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
35 USC § 102
The rejection of claims 1-5, 14, 18 under 35 U.S.C. 102a1 as being anticipated by Fu (WO 2018106997) was withdrawn. Fu introduced pluripotent cells into a microfluidic device in E6 basal medium comprising BMP4 (pg 6, lines 3-4; pg 7, lines 4-5; pg 11, lines 1-6; pg 19, lines 2-3; Fig. 7 & 13). The microfluidic channels in Fig. 13 described on pg 11, lines 1-10, of Fu have the same structure as the microfluidic device comprising a culture and fluidic channel in claim 1. Fu taught introducing cells into the “cell culture channel” and the culture media into the “induction channel” and “cell loading channel” as required in claim 1 because they are the same channel. The cells were cultured for a period of time such that a “posteriorized embryonic-like sac” was obtained as required in claim 1 because Fu obtained amniotic tissue in the shape of a “sac” from the pluripotent cells (pg 21, lines 15-25). Fu taught the tissue obtained was similar to posteriorizing primitive streak tissue (Fig 7 description on pg 6; Example 2 last 6 paragraphs) which is equivalent to “P-ELS” tissue as required in claim 1. The “sac” had a “single layer of amniotic ectoderm-like cells at a pole” and a “stratified epiblast-like epithelium comprising pre-posterior streak-EPI cells at a pole” as required in claim 1 because the metes and bounds of the cells encompassed by the phrases cannot be determined (see 112/2nd) and because Fu taught poled amniotic tissue having the structures claimed:
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Fu cultured the cells in media containing BMP4 (pg 6, lines 3-4; pg 7, lines 4-5; pg 11, lines 1-6; pg 19, lines 2-3; Fig. 7 & 13) and noggin (pg 17, line 10; pg 21, line 4) which “alter BMP” as encompassed by claim 2. Fu cultured the cells in media containing BMP4 (pg 6, lines 3-4; pg 7, lines 4-5; pg 11, lines 1-6; pg 19, lines 2-3; Fig. 7 & 13) and treated cells with noggin (pg 17, line 10; pg 21, line 4) which is a component selected from the group “BMP4, noggin” as required in claim 3. Fu treated cells with BMP4 and noggin “after a defined period of time” as required in claim 4 because any time is a “after a defined period of time”. Fu cultured cells for 2 days (Fig. 6) which is 0-120 hours as required in claim 5. Fu used Matrigel which is a “gel matrix” as required in claim 14. The Matrigel is in a “plurality of posts” as required in claim 14 because the metes and bounds are unclear (see 112/2nd). Fu taught the cells expressed TFAP2A (Example 2) as required in claim 18. However, while Fu used mTesR1 medium comprising BMP4, Fu did not teach using FGF2 as newly required in claim 1 (previously in now-canceled claim 13).
The rejection of claims 1-5, 14, 18 under 35 U.S.C. 102a1 as being anticipated by Fu (11672832) was withdrawn. The effective filing date of the claims is 9-9-19, the filing date of provisional application 62897565 (Fu & Zheng). The effective filing date of 11672832 (by another inventive entity - Fu, Gumucio, Shao, Taniguchi, Zhen, & Esfahani) is at least 6-6-19, the 371c1 filing date of PCT/US2017/065261), and possibly 12-8-17, the filing date of 16467154. Fu differentiated pluripotent cells into posterior amniotic tissue using medium (claim 1; Example 1) using a microfluidic device (col. 16, Example 3, lines 30-33). The microfluidic channels described by Fu and cited in col. 16, lines 30-33, have the same structure as the microfluidic device comprising a culture and fluidic channel in claim 1. The cells were introduced into the culture channel and the culture media was introduced into the fluidic channel as required in claim 1 because they are the same channel. The cells were cultured for a period of time such that embryo-like tissue was obtained as required in claim 1 because Fu differentiated pluripotent cells into posterior amniotic tissue (Examples 1 & 3). Fu taught introducing cells into the “cell culture channel” and the culture media into the “induction channel” and “cell loading channel” as required in claim 1 because they are the same channel. The cells were cultured for a period of time such that a “posteriorized embryonic-like sac” was obtained as required in claim 1 because Fu obtained amniotic tissue in the shape of a “sac” from the pluripotent cells (pg 21, lines 15-25). Fu taught the tissue obtained was similar to posteriorizing primitive streak tissue (Fig 7 description on pg 6; Example 2 last 6 paragraphs) which is equivalent to “P-ELS” tissue as required in claim 1. The “sac” had a “single layer of amniotic ectoderm-like cells at a pole” and a “stratified epiblast-like epithelium comprising pre-posterior streak-EPI cells at a pole” as required in claim 1 because the metes and bounds of the cells encompassed by the phrases cannot be determined (see 112/2nd) and because Fu taught poled amniotic tissue having the structures claimed. Fu treated cells with BMP4 (col. 8, line 26) or noggin (pg 17, line 10; pg 21, line 4) which “alter BMP” as encompassed by claim 2.
Fu cultured the cells in media containing BMP4 and treated cells with noggin which is a component selected from the group “BMP4, noggin” as required in claim 3. Fu treated cells with BMP4 and noggin “after a defined period of time” as required in claim 4 because any time is a “after a defined period of time”. Fu cultured cells for 2 days (Fig. 6) which is 0-120 hours as required in claim 5. Fu used gel matrixes (col. 7, line 55, through col. 3, line 3: Examples; claims) as required in claim 14. The Matrigel is in a “plurality of posts” as required in claim 14 because the metes and bounds are unclear (see 112/2nd). Fu taught the cells expressed TFAP2A (Example 2; claim 6) as required in claim 18. However, while Fu used mTesR1 medium comprising BMP4, Fu did not teach using FGF2 as newly required in claim 1 (previously in now-canceled claim 13).
Claim Rejections - 35 USC § 103
A) Claims 1-5, 14 remain rejected under 35 U.S.C. 103 as being unpatentable over Fu (WO 2018106997) or Fu (11672832) in view of Takasato (12134785)
The effective filing date of the claims is 9-9-19, the filing date of provisional application 62897565 (Fu & Zheng).
Fu (‘997) introduced pluripotent cells into a microfluidic device in E6 basal medium comprising BMP4 (pg 6, lines 3-4; pg 7, lines 4-5; pg 11, lines 1-6; pg 19, lines 2-3; Fig. 7 & 13). The microfluidic channels in Fig. 13 described on pg 11, lines 1-10, of Fu have the same structure as the microfluidic device comprising a culture and fluidic channel in claim 1. Fu taught introducing cells into the “cell culture channel” and the culture media into the “induction channel” and “cell loading channel” as required in claim 1 because they are the same channel. The cells were cultured for a period of time such that a “embryonic sac” was obtained as required in claim 1 because Fu obtained amniotic tissue in the shape of a “sac” from the pluripotent cells (pg 21, lines 15-25). Fu taught the tissue obtained was similar to posteriorizing primitive streak tissue (Fig 7 description on pg 6; Example 2 last 6 paragraphs) which is equivalent to “embryonic sac” tissue as required in claim 1. The “sac” inherently MUST have “a single layer of amniotic ectoderm cells that express TFAP2A at a first pole” and an “epiblast epithelium comprising epithelial cells that express CDX2 and T at a second pole exposed to basal medium” as required in claim 1 because the metes and bounds of the cells encompassed by the phrases cannot be determined (see 112/2nd) and because Fu taught poled amniotic tissue having the structures claimed:
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Fu cultured the cells in media containing BMP4 (pg 6, lines 3-4; pg 7, lines 4-5; pg 11, lines 1-6; pg 19, lines 2-3; Fig. 7 & 13) and noggin (pg 17, line 10; pg 21, line 4) which as encompassed by claim 2.
Fu cultured the cells in media containing BMP4 (pg 6, lines 3-4; pg 7, lines 4-5; pg 11, lines 1-6; pg 19, lines 2-3; Fig. 7 & 13) and treated cells with noggin (pg 17, line 10; pg 21, line 4) which is a component selected from the group “BMP4, noggin” as required in claim 3.
Fu treated cells with BMP4 and noggin “after a defined period of time” as required in claim 4 because any time is a “after a defined period of time”.
Fu cultured cells for 2 days (Fig. 6) which is 0-120 hours as required in claim 5.
Fu used Matrigel which is a “gel matrix” as required in claim 14. The Matrigel is in a “plurality of posts” as required in claim 14 because the metes and bounds are unclear (see 112/2nd).
Fu taught the cells expressed TFAP2A (Example 2) as required in claim 1.
The effective filing date of 11672832 (by another inventive entity - Fu, Gumucio, Shao, Taniguchi, Zhen, & Esfahani) is at least 6-6-19, the 371c1 filing date of PCT/US2017/065261), and possibly 12-8-17, the filing date of 16467154.
Fu differentiated pluripotent cells into posterior amniotic tissue using medium (claim 1; Example 1) using a microfluidic device (col. 16, Example 3, lines 30-33). The microfluidic channels described by Fu and cited in col. 16, lines 30-33, have the same structure as the microfluidic device comprising a culture and fluidic channel in claim 1. The cells were introduced into the culture channel and the culture media was introduced into the fluidic channel as required in claim 1 because they are the same channel. The cells were cultured for a period of time such that embryonic sac tissue was obtained as required in claim 1 because Fu differentiated pluripotent cells into posterior amniotic tissue (Examples 1 & 3). Fu taught introducing cells into the “cell culture channel” and the culture media into the “induction channel” and “cell loading channel” as required in claim 1 because they are the same channel. The cells were cultured for a period of time such that a “embryonic sac” was obtained as required in claim 1 because Fu obtained amniotic tissue in the shape of a “sac” from the pluripotent cells (pg 21, lines 15-25). Fu taught the tissue obtained was similar to posteriorizing primitive streak tissue (Fig 7 description on pg 6; Example 2 last 6 paragraphs) which is equivalent to “embryonic sac” tissue as required in claim 1. The “sac” inherently MUST have “a single layer of amniotic ectoderm cells that express TFAP2A at a first pole” and an “epiblast epithelium comprising epithelial cells that express CDX2 and T at a second pole exposed to basal medium” as required in claim 1 because the metes and bounds of the cells encompassed by the phrases cannot be determined (see 112/2nd) and because Fu taught poled amniotic tissue having the structures claimed. Fu taught the cells expressed TFAP2A (Example 2; claim 6) as required in claim 1.
Fu treated cells with BMP4 (col. 8, line 26) or noggin (pg 17, line 10; pg 21, line 4) as encompassed by claim 2.
Fu cultured the cells in media containing BMP4 and treated cells with noggin which is a component selected from the group “BMP4, noggin” as required in claim 3.
Fu treated cells with BMP4 and noggin “after a defined period of time” as required in claim 4 because any time is a “after a defined period of time”.
Fu cultured cells for 2 days (Fig. 6) which is 0-120 hours as required in claim 5.
Fu used gel matrixes (col. 7, line 55, through col. 3, line 3: Examples; claims) as required in claim 14. The Matrigel is in a “plurality of posts” as required in claim 14 because the metes and bounds are unclear (see 112/2nd).
Fu did not teach using FGF2 as required in claim 1.
However, Takasato taught differentiating pluripotent cells into posterior amniotic tissue (col. 14, line 63, through col. 15, line 15) using in BMP4 and activin (col. 12, lines 12-20) and using FGF2 (e.g. col. 12, line 64).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to differentiate pluripotent cells into posterior amniotic tissue in a microfluidic device as described by Fu (‘997) or Fu (‘832) using BMP4 and activin or FGF2 as described by Takasato. Those of ordinary skill in the art at the time of filing would have been motivated to do so to improve the production of posterior amniotic tissue.
Response to arguments
Applicants argue the combined references did not teach using two different mediums introduced into different channels. Applicants’ argument is not persuasive because Fu used basal medium plus BMP4 and the combined teachings of Fu and Takasato taught using BMP4 and FGF2.
Conclusion
No claim is 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.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO’s Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public.
For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
If attempts to reach the examiner are unsuccessful, the examiner's supervisor, Tracy Vivlemore, can be reached on 571-272-2914.
The official fax number for this Group is (571) 273-8300.
Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638