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 16 and 19 have been canceled. Claims 1-15, 17, 18, 20-22 are pending.
Election/Restrictions
Claim 22 is drawn to a kit comprising the composition of claim 1 and should have been included with Group I in the restriction sent 10-15-25.
Applicant's election with traverse of Group I, claims 1-3, 6-11, 22 in the reply filed on 12-12-25 is acknowledged. The traversal is on the ground(s) that Groups III and IV are dependent upon claim 1. This is not found persuasive because Group III requires a search of active steps for making the composition of claim 1, but the composition of claim 1 does not necessarily have to be made using the method steps of Group III. Group IV is a method of using the composition of claim 1 for treatment, but the composition can be used for research in vitro and does not have to be used for treatment. A search of all the steps in Groups III and IV together with the composition of Group I together would be undue. The requirement is still deemed proper and is therefore made FINAL.
Claims 4, 5, 12-15, 17, 18, 20, 21 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12-12-25.
Claims 1-3, 6-11, 22 are under consideration.
Claim objections
The composition of claim 1 comprises three things which can be set forth more clearly as: ---A composition comprising: i) mammalian thymic stromal cells; ii) mammalian thymic epithelial cells; and iii) mammalian hematopoietic cells---. Please use “i)”, “ii)” and “iii)” for ease of examination, discussion, and prosecution.
It is unclear whether the phrase “expressing one or more marker comprising EPCAM, CD205, and FOXN1” is limited to the “thymic epithelial cells” or whether it applies to both the “thymic stromal cells” and the “thymic epithelial cells”.
Use of “one more marker comprising EPCAM, CD205, and FOXN1” together with “expressing one or more of CD34+ and CD45+” together in claim 1 makes it confusing. Use of “+” is redundant if the cells express CD34 or CD45.
If applicants are attempting to invoke Markush group language, then the phrase “selected from the group consisting of” is missing. It is unclear whether the “one more marker comprising EPCAM, CD205 and FOXN1” applies to just the thymic epithelial cells or both the thymic stromal cells and thymic epithelial cells. It would be simpler and clearer to simply say: ---A composition comprising: i) mammalian thymic stromal and epithelial cells that express EPCAM, CD205 or FOXN1; and ii) mammalian hematopoietic cells that express CD34 or CD45---. However, since hematopoietic cells inherently MUST express CD34, it is unclear how the limitation of expressing CD34 further limits the hematopoietic cells. This suggestion is not to be construed as allowable. It is merely set forth to clarify applicants’ invention in an attempt to expedite prosecution.
It is unclear how the phrase “HPCs are derived from a subject to be treated” in claim 2 further limits the HPCs in claim 1. The concept of “a subject” in claim 2 is broader than “mammalian” cells in claim 1, and any subject can be “treated” for anything, so it is unclear how the phrase further limits the cells. It is also unclear when HPCs are “derived”. It is unclear whether applicants are attempting to invoke product-by-process language within the method claim or whether applicants are attempting to limit the HPCs to those having specific structures/functions. It is unclear whether applicants are attempting to claim an active step of isolating the HPCs from a mammal with disease, an active step of isolating the HPCs from cord blood, an active step of differentiating pluripotent cells into the HPCs, or differentiating “other cell populations” into the HPCs, or if there is some structure/function that is inherent in HPCs isolated “from cord blood, from differentiated pluripotent stem cells, or from other stem cell populations”
It is unclear how the phrase “cells are derived from mammalian thymi or differentiated HPSCs (human pluripotent stem cells) or other stem cells or splanchnic mesenchyme” in claim 4 further limits the thymic or HPCs in claim 1. It is unclear when cells are “derived”. It is unclear whether applicants are attempting to invoke product-by-process language within the method claim or whether applicants are attempting to limit the cells to those having specific structures/functions. It is unclear whether applicants are attempting to claim an active step of isolating the cells from mammalian thymuses, an active step of isolating (i.e. differentiating) the cells from human pluripotent cells, an active step of differentiating stem cells or “splanchnic mesenchyme” into the cells, or if there is some structure/function that is inherent in cells isolated “from mammalian thymuses” or differentiated from human pluripotent cells, stem cells, or “splanchnic mesenchyme”.
HPSCs should be spelled out before being abbreviated, not the other way around as in claim 6.
It is unclear how the composition cultured for 1 week to about 3 months in claim 7 further limits the structure or function of the cells in the composition of claim 1. This is an active step and invokes product-by-process language, but it is unclear how the structures/functions of the cells in claim 7 differ from the structures/functions of the cells in claim 1.
Use “(1)” in the phrase “one (1)” in claim 7 is redundant.
Use “(3)” in the phrase “three (3)” in claim 7 is redundant.
Claim 8 lists “AIRE” twice. Please delete one of them.
Use of singular “AIRE, CD205, EPCAM…” in claim 8 along with plural “tissue-restricted antigens (TRAs)” in the phrase “express one or more of AIRE,… (TRAs)” is grammatically incorrect. Please use the phrase ---a tissue-restricted antigen---.
Use of parentheses in claim 8 to describe HLA-DQ as being Class II makes the claim unclear. HLA-DQ MUST inherently be a Class to HLA molecule, so “(Class II)” is redundant.
If applicants are attempting to invoke Markush group language in claim 8, then the phrase “selected from the group consisting of” is missing. As written, the phrase uses “and” which makes it confusing, so it is unclear if all of the markers must be expressed or if only one of the markers must be expressed. It would be simpler to say ---“wherein the thymic stromal [and? or?] epithelial cells express AIRE, CD205,… … or a tissue-restricted antigen (TRA)--- (assuming applicants are attempting to recite open claim language).
If applicants are attempting to invoke Markush group language in claim 9, then the phrase “selected from the group consisting of” is missing. As written, the phrase uses “and” which makes it confusing, so it is unclear if all of the markers must be expressed or if only one of the markers must be expressed. It would be simpler to say ---“wherein the TRA is INS, IA2, GAD1, myelin basic protein, or thyroglobulin--- (assuming applicants are attempting to recite open claim language).
If applicants are attempting to invoke Markush group language in claim 10, then the phrase “selected from the group consisting of” is missing. As written, the phrase uses “and” which makes it confusing, so it is unclear if all of the markers must be expressed or if only one of the markers must be expressed. It would be simpler to say ---“wherein the thymic cells or HPCs express CD5, CD7,… …CD150--- (assuming applicants are attempting to recite open claim language).
If applicants are attempting to invoke Markush group language in claim 11, then the phrase “selected from the group consisting of” is missing. As written, the phrase uses “and” which makes it confusing, so it is unclear if all of the markers must be expressed or if only one of the markers must be expressed. It would be simpler to say ---“wherein the thymic stromal cells express CD105, CD90,… or TE-7--- (assuming applicants are attempting to recite open claim language).
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 3, 11 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.
The specification lacks written description for any cell expressing PDGFRα as broadly encompassed by claim 3 other than mesenchymal cells. PDGFRα is a marker for mesenchymal cells (para 11; para 30; end of para 41; para 42; para 80, et al.). The specification does not correlate PDGFRα expression to any thymic, liver, hematopoietic, skin, lung, muscle, reproductive, or stem cells as broadly encompassed by claim 3. Accordingly, the concept lacks written description.
The specification lacks written description for any thymic stromal cell expressing PDGFRβ as broadly encompassed by claim 11 other than mesenchymal cells. PDGFRβ is a marker for mesenchymal cells (para 7). The specification does not correlate PDGFRβ expression to any thymic stromal cells as required in claim 3. Accordingly, the concept lacks written description.
The specification lacks written description for thymic cells expressing any TRAs as required in claims 8 and 9. Tissue-restricted antigens (TRAs) include insulin, MBP, thyroglobin, and any other tissue-specific antigen, e.g. pancreas-, eye-, hair-, et al. specific antigen. The specification is limited to thymic cells expressing thymic-specific antigens, e.g. AIRE. The specification does not correlate any thymic cells expressing thymic-specific antigens thymic cells expressing insulin, MBP, thyroglobin, or any pancreas-, eye-, hair-, et al. specific antigen. Accordingly, the concept of TRAs in claims 8 and 9 lacks written description.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 6-11, 22 are rejected under 35 U.S.C. 102a1 as being anticipated by Vizcardo (20200270571).
Vizcardo taught a composition comprising mammalian thymic stromal (para 53, 58, 59; claim 1) and thymic epithelial (para 21, 42, 48, 54-56, 58, 65, 78, 105, 109, 110, 116, 119, 120, 122; claim 1) cells and mammalian CD34+ human cord blood cells (HBCs) (para 10, 13, 71, 110).
Vizcardo taught the HPCs were from cord blood (para 10, 13, 71, 110) as required in claim 2.
Vizcardo taught the composition comprised MSCs (para 4, 58, 62, 72, 107, 123, 124) which inherently MUST express PDGFRα as required in claim 3.
Vizcardo taught the cells were derived from mammalian thymi, HPSC, stem cells as required in claim 6 for reasons set forth above.
Vizcardo taught the cells were cultured for days, weeks, and months (para 15-21, 28-30, 32, 34, 36, 38, 40, 43, 44, 47-49, 52, 73, 105-107, 110, 112, 114-116, 119, 120, 122, 127, 129, 131, 133, 135) as required in claim 7.
Vizcardo taught the cells expressed DDL4 (para 4, 39, 55, 56, 63, 122, 134, 135; claim 1) and FOXN1 (para 13, 14, 18-20, 29, 48, 50, 65, 110-112, 119, 128, 129; claims 4, 7) and TRA (para 46) and CD205 (para 55) as required in claim 8.
Claim 9 has been included because it further limits the TRA in claim 8 without limiting the claim to cells that express “one or more of INS, IA2, GAD, myelin basic protein, and thyroglobin” and because the cells of Vizcardo inherently MUST express INS, IA2, GAD, myelin basic protein, or thyroglobin because they were obtained using means described by applicants as being part of the invention.
Vizcardo taught the cells express CD34 for reasons set forth above (para 10, 13) as required in claim 10. The cells may also express TCRa or b or CD49 (para 63) as required in claim 10.
The cells of Vizcardo inherently MUST express CD105, CD90, CD73, VIM, PDGFRβ, FGF7, FGF10, or TE7 as required in claim 11 because they were obtained using means described by applicants as being part of the invention.
Claim 22 has been included because it is drawn to a kit comprising the composition of claim 1 which is the same as the composition described by Vizcardo.
Claims 1, 3, 6-11, 22 are rejected under 35 U.S.C. 102a1 as being anticipated by Blackburn (WO 02051988).
Blackburn taught a composition comprising mammalian thymic epithelial cells and hematopoietic cells (claims 17, 22, 23) and adding thymic non-epithelial cells of the thymic stromal (pg 19, line 6). The thymic epithelial cells express FOXN1 (Fig. 3). Hematopoietic cells inherently MUST express CD34 because that is what defines them as hematopoietic cells. This is equivalent to the composition of claim 1.
Blackburn taught the composition comprised MSCs (claim 14) which inherently MUST express PDGFRα as required in claim 3.
Blackburn taught the cells were derived from mammalian thymi, HPSC, stem cells as required in claim 6 for reasons set forth above.
Blackburn taught the cells were cultured for days, weeks, and months (pg 28, line 3; pg 28, line 26; pg 36, line 19) as required in claim 7.
The cells of Blackburn inherently MUST express one of the markers in claim 8 because they were obtained using means described by applicants as being part of the invention.
Claim 9 has been included because it further limits the TRA in claim 8 without limiting the claim to cells that express “one or more of INS, IA2, GAD, myelin basic protein, and thyroglobin” and because the cells of Blackburn inherently MUST express INS, IA2, GAD, myelin basic protein, or thyroglobin because they were obtained using means described by applicants as being part of the invention.
Blackburn taught the cells express CD34 for reasons set forth above as required in claim 10.
The cells of Blackburn inherently MUST express CD105, CD90, CD73, VIM, PDGFRβ, FGF7, FGF10, or TE7 as required in claim 11 because they were obtained using means described by applicants as being part of the invention.
Claim 22 has been included because it is drawn to a kit comprising the composition of claim 1 which is the same as the composition described by Blackburn.
Claims 1, 6-11, 22 are rejected under 35 U.S.C. 102a1 as being anticipated by Parent (9850465).
Parent taught a composition comprising mammalian thymic epithelial cells and hematopoietic cells (col. 38, line 10). The thymic epithelial cells express FOXN1 (col. 3, line 29). The thymic epithelial cells are thymic stromal cells because they are “the main component of the thymic stroma (col. 1, lines 29-31). Hematopoietic cells inherently MUST express CD34 because that is what defines them as hematopoietic cells. This is equivalent to the composition of claim 1.
Blackburn taught the cells were derived from mammalian thymi, HPSC, stem cells as required in claim 6 for reasons set forth above.
Claim 7 has been included because culturing the cells for a week to 3 months does not alter the structure/function of the cells.
The cells of Parent inherently MUST express one of the markers in claim 8 because they were obtained using means described by applicants as being part of the invention.
Claim 9 has been included because it further limits the TRA in claim 8 without limiting the claim to cells that express “one or more of INS, IA2, GAD, myelin basic protein, and thyroglobin” and because the cells of Parent inherently MUST express INS, IA2, GAD, myelin basic protein, or thyroglobin because they were obtained using means described by applicants as being part of the invention.
Parent taught the cells express CD34 for reasons set forth above as required in claim 10.
The cells of Parent inherently MUST express CD105, CD90, CD73, VIM, PDGFRβ, FGF7, FGF10, or TE7 as required in claim 11 because they were obtained using means described by applicants as being part of the invention.
Claim 22 has been included because it is drawn to a kit comprising the composition of claim 1 which is the same as the composition described by Parent.
Conclusion
No claim is allowed.
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.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638