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 3, 4, 6 have been canceled. Claim 13 has been added. Claims 1, 2, 5, 7-13 are pending.
Applicant's arguments filed 5-13-26 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 Objections
The steps in claim 1 should be labeled a), b), c) for clarity and ease of discussion.
The first “differentiating” by “culturing” in claim 1 is actually one step and can be written more succinctly. The active step and result should be set forth more clearly. The step can be written more accurately as ---culturing mammalian pluripotent cells in medium comprising [bFGF, VGFA, SCF, BMP4, and CHIR] such that mesodermal cells are obtained---.
The second “differentiating” by “culturing” in claim 1 is also one step and can be written more succinctly for reasons set forth above as --- culturing the mesodermal cells in medium comprising [TOP, EPO, IGF1, bFGF, VEGFA, SCF, FLT3L, GCSF, and IL6] such that early hemogenic endothelial (EHE) cells are obtained---.
The third “differentiating” by “culturing” in claim 1 is also one step and can be written more succinctly for reasons set forth above as --- culturing the EHE cells in medium comprising [IL5, IL5, DLL, bFGF, VEGFA, SCF, FLT3L, GCSF, IL6, IGF1, and IL15] such that late hemogenic endothelial (LHE) cells are obtained---.
Claim 2 does not make sense because “somatic cell nuclear transfer derived stem cells” and “adult derived mesenchymal stem cells” are not pluripotent cells. Claim 2 can be written more succinctly as ---wherein the pluripotent cell is an embryonic stem cell or an induced pluripotent stem cell---.
Claim 5 can be written more succinctly as ---wherein the EHE cell a) has morphological characteristics of rod cells; b) fluoresces yellow; c) has a doubling rate of 15-35 hours; or d) expresses [CD31, TIE2, CD144, or CD34]---. Although this does not make sense because other cells have morphological characteristics of rod cells (especially rod cells), fluoresce yellow, have a doubling rate of 15-35 hours, and express CD31, TIE2, CD144, or CD34. The features claimed, neither individually or collectively, capture the features that are unique to and define EHE cells.
Claim 6 can be written more succinctly as ---wherein the LHE cell a) has morphological characteristics of cobblestone cells; or b) expresses [CD31,… …or FLK1]---. Although this does not make sense because other cells have morphological characteristics of cobblestone cells (especially cobblestone cells), and express CD31, CD144, or CD34. The features claimed, neither individually or collectively, capture the features that are unique to and define LHE cells.
Claim Rejections - 35 USC § 112
Written Description
Claims 1, 2, 5, 7-12 remain and claim 13 is 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.
The specification lacks written description for differentiating pluripotent cells into mesoderm cells, then “early hemogenic endothelial cells”, then “late hemogenic endothelial cells” or “lymphoid lineage blood cells” as broadly encompassed by claim 1 other than hematopoietic cells, mesoderm cells, hemogenic endothelial cells, then T-cells and NK cells. Claim 1 encompasses obtaining any “lymphoid lineage blood cell” from mammalian pluripotent cells. The specification is limited culturing mammalian pluripotent cells in medium containing bFGF, VEGF, and SCF such that mesodermal cells are obtained; ii) culturing the mesodermal cells in medium containing TPO, EPO, and IGF1 such that hemogenic endothelial (HE) cells are obtained; and iii) culturing the HE cells in medium containing IL5, IL7 and DLL such that T-cells and NK cells are obtained (Examples). The specification does not correlate obtaining HE cell to obtaining “early” HE cells as required in claim 1. The specification does not correlate obtaining T-cells and NK cells to obtaining any “late” HE cells as required in claim 1. Accordingly, the claim lacks written description for the breadth claimed.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
The specification does not teach putting bFGF, VEGF, SCF, ascorbic acid, BMP4, and CHIR in the first medium as required in item a) of claim 1. Original claim 3 is limited to using bFGF, VEGF, SCF, ascorbic acid, and BMP4. The specification does not teach using bFGF, VEGF, SCF, ascorbic acid, BMP4, and CHIR as claimed. Accordingly, the concept is new matter.
The specification does not teach putting IL5, IL7, DLL, bFGF, VEGF, SCF, FLT3L, GCSCF, IL6, IGF1 and IL15 in the 3rd medium as required in item c) of claim 1. Original claim 6 is limited to using IL5, IL7, DLL, and “bFGF, VEGF, SCF, FLT3L, GCSCF, and IL6, IGF1, IL15; or a mixture of the aforementioned factors”. The specification does not teach using IL5, IL7, DLL, bFGF, VEGF, SCF, FLT3L, GCSCF, IL6, IGF1 and IL15 to make T-cell and NK cells as encompassed by claim 1. Accordingly, the concept is new matter.
Indefiniteness
Claims 1, 2, 5, 7-12 remain and claim 13 is 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 “early hemogenic endothelial cells” in claim 1 cannot be determined. The specification and the art at the time of filing do not teach the structures/functions that define when hemogenic endothelial (HE) cells are “early”. The term “early” is relative and at the discretion of the person of skill and may be different for everyone. Time and chronology CANNOT be used to describe the structure and functions of hemogenic endothelial cells. Perhaps markers can be used to define when they are “early” HE cells; however, such markers are missing from the specification and the art at the time of filing. It is unclear what functions define HE cells as “early”. Without such a definition, the metes and bound of when HE cells are “early” cannot be determined, especially when they are in vitro and not in context of an embryo in utero. Accordingly, those of skill would not be able to determine when they were infringing on the claim.
Response to arguments
Applicants argue the phrase refers to a chronological, sequential distinction within the culture process rather than a subjective judgement and point to pg 15. Applicants’ argument is not persuasive because that explanation makes it even MORE unclear. Time and chronology CANNOT be used to describe the structure and functions of hemogenic endothelial cells. Perhaps markers can be used to define when they are “early” HE cells; however, such markers are missing from the specification and the art at the time of filing. It is unclear what functions define HE cells as “early”. Without such a definition, the metes and bound of when HE cells are “early” cannot be determined, especially when they are in vitro and not in context of an embryo in utero.
B) The metes and bounds of “late hemogenic endothelial cells” in claim 1 cannot be determined. The specification and the art at the time of filing do not teach the structures/functions that define when hemogenic endothelial (HE) cells are “late”. The term “late” is relative and at the discretion of the person of skill and may be different for everyone. Time and chronology CANNOT be used to describe the structure and functions of hemogenic endothelial cells. Perhaps markers can be used to define when they are “late” HE cells; however, such markers are missing from the specification and the art at the time of filing. It is unclear what functions define HE cells as “late”. Without such a definition, the metes and bound of when HE cells are “late” cannot be determined, especially when they are in vitro and not in context of an embryo in utero. Accordingly, those of skill would not be able to determine when they were infringing on the claim.
Response to arguments
Applicants argue the phrase refers to a chronological, sequential distinction within the culture process rather than a subjective judgement and point to pg 15. Applicants’ argument is not persuasive because that makes it even MORE unclear. Time and chronology CANNOT be used to describe the structure and functions of hemogenic endothelial cells. Structures and functions are required to define when they are “late” HE cells which is missing from the specification and the art at the time of filing. Without such a definition, the metes and bound of when HE cells are “late” cannot be determined.
C) Claim 5 remains indefinite because it is unclear when an EHE cell has “rod-type morphological characteristics”. Claim 1 requires obtaining lymphoid lineage blood cells from mesodermal, EHE, and LHE cells, but rod cells are in the eye and not mesodermal, EHE, LHE, or blood cells. Or perhaps applicants are attempting to set forth the shape, but the metes and bounds of when a “rod-like” shape has been obtained cannot be determined. It is also unclear when cells have “bright yellow light” as required in item b) because cells don’t have lights. If it is simply a color, it is unclear when a yellow cell is “bright yellow” as claimed. Accordingly, those of skill would not be able to determine when they were infringing on the claim.
Response to arguments
Applicants argue those of skill would not confuse these cells with rod cells. Applicants’ argument is not persuasive. If they are not rod cells, then it is unclear what they ARE in context of HE cells. The definition of when cells are “rod-like” is not defined in the specification or the art at the time of filing.
Applicants’ discussion of “bright yellow” is noted but does not discuss when yellow fluorescence is “bright”. The specification does not define when yellow fluorescence is “bright”.
D) Claim 7 is indefinite because it is unclear when a LHE cell has “cobblestone-type morphological characteristics”. Perhaps applicants are attempting to set forth the shape, but the metes and bounds of when a “cobblestone-like” shape has been obtained cannot be determined, especially when the cell is isolated and not amongst other cells. It is unclear whether any monolayer of cells will do or if a particular shape of cell is required. It is unclear if any overlap of cells is encompassed by the claim or the cells must be a monolayer without any overlap. If there is a shape associated with cobblestone, it is unclear if the “cobblestone” cells must be irregular or if they can be circular. Accordingly, those of skill would not be able to determine when they were infringing on the claim.
Response to arguments
Applicants argue the phrase was well-established because it was used in 12545945 and 20240131077. Applicants’ argument is not persuasive. ‘077 describes the cobblestone morphology of RPEs, but does not define when RPEs are “cobblestone” or the metes and bounds of when they are “like” cobblestones. There is no definition of the metes and bounds of when LHE, T-cells, or NK cells have “cobblestone-like type morphological characteristics”. It is unclear whether any monolayer of cells will do or if a particular shape of cell is required. It is unclear if any overlap of cells is encompassed by the claim or the cells must be a monolayer without any overlap. If there is a shape associated with cobblestone, it is unclear if the “cobblestone” cells must be irregular or if they can be circular.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 2, 5, 7-12 under 35 U.S.C. 103 as being unpatentable over Rajesh (20100279403) in view of Themeli (20160009813) and Garelick (WO 2016123100), Valamehr (AU 2016211671) has been withdrawn because the prior art did not reasonably teach or suggest the combination of growth factors in the three steps of claim 1.
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.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
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