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 23 and 24 have been added. Claims 1-15, 17, 18, 20-24 are pending.
Election/Restrictions
Applicants elected Group I, claims 1-3, 6-11, 22, with traverse in the reply filed on 12-12-25.
Claims 4, 5, 12-15, 17, 18, 20, 21 remain withdrawn from further consideration.
Claims 1-3, 6-11, 22-24 are under consideration.
Applicant's arguments filed 6-9-26 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 composition of claim 1 comprises three things which can be set forth more clearly as: ---A composition comprising: i) isolated mammalian thymic stromal cells; ii) isolated mammalian thymic epithelial cells that express EPCAM, CD205, or FOXN1; iii) isolated mammalian hematopoietic progenitor cells that express CD34 or CD45; and iv) media---.
Use of “one more marker comprising EPCAM, CD205, and FOXN1” together with “CD34+ and CD45+ [HPCs}” together in claim 1 makes it confusing. Use of “+” is redundant if the cells express CD34 or CD45. Use the same format to describe the expression patterns of thymic epithelial cells and HPCs, just say --- isolated mammalian thymic epithelial cells that express EPCAM, CD205, or FOXN1---.
The phrase “wherein the thymic epithelial cells” in item ii) of claim 1 is redundant.
If applicants are attempting to invoke Markush group language in the phrase “one more marker comprising EPCAM, CD205 and FOXN1” in claim 1, then the phrase “selected from the group consisting of” is missing.
Since hematopoietic progenitors inherently MUST express CD34, it is unclear how the limitation of expressing CD34 further limits the hematopoietic progenitors.
This suggestion is not to be construed as allowable. It is merely set forth to clarify applicants’ invention in an attempt to expedite prosecution.
The term “subject” in the phrase “mammalian subject” in claim 2 is redundant. Just say mammal.
It is unclear how the phrase “obtaining the HPCs from a subject to be treated for a condition” in claim 2 further limits the HPCs in claim 1. The concept of “a mammalian subject” in claim 2 is broad because any mammal can be “treated” for anything, so it is unclear how the phrase further limits the cells. 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 “thymic mesenchymal cells are derived from mammalian thymi or differentiated human pluripotent stem cells (HPSCs) or other stem cells or splanchnic mesenchyme” in claim 6 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”.
It is unclear how the composition that “was 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 of singular “one or more of AIRE, CD205, EPCAM…” in claim 8 along with “one or more of a tissue-restricted antigens (TRAs)” in claim 8 does not make sense.
If applicants are attempting to invoke Markush group language in claim 8, then the phrase “selected from the group consisting of” is missing. Just list them all in the alternative which implies and encompasses “one or more”.
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). Just list them all in the alternative which implies and encompasses “one or more”.
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). Just list them all in the alternative which implies and encompasses “one or more”.
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). Just list them all in the alternative which implies and encompasses “one or more”.
Claim Rejections - 35 USC § 112
Claims 3, 8, 9, 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 “plurality of thymic mesenchymal cells expressingPDGFRa wherein the plurality of thymic mesenchymal cells expressing PDGFRa are in addition to the composition, or wherein the plurality ofthymic mesenchymal cells expressing PDGFRa~ are the plurality ofmammalian thymic stromal cells” 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 teach anything other than thymic epithelial cells that are thymic mesenchymal cells that express PDGFR or that they are in addition to the thymic epithelial cells. Applicants do not teach a composition comprising: i) isolated mammalian thymic stromal cells; ii) isolated mammalian thymic epithelial cells that express EPCAM, CD205, or FOXN1; iii) isolated mammalian hematopoietic progenitor cells that express CD34 or CD45; iv) media; and v) thymic MSCs expressing PDGFRa as required in 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 7. 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.
Response to arguments
Applicants argue the amendment overcomes the rejection. Applicants’ argument is not persuasive for reasons set forth above.
Claim Rejections - 35 USC § 102
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.
Response to arguments
Applicants argue Vizcardo is limited to skeletal derived stromal cells and does not describe thymic cells having the structure claimed. Applicants’ argument is not persuasive. 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 is not limited to skeletal stromal cells.
Applicants point to para 53 and 58 of Vizcardo. Applicants’ argument is not persuasive for reasons set forth above.
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.
Response to arguments
Applicants argue Blackburn does not teach the composition claimed (pg 9). Applicants’ argument is not persuasive for reasons set forth above.
Applicants’ discussion of dependent claims is noted. Applicants’ argument is not persuasive for reasons set forth above.
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.
Response to arguments
Applicants argue Parent does not teach the composition claimed (pg 10). Applicants’ argument is not persuasive for reasons set forth above.
Applicants’ discussion of dependent claims is noted. Applicants’ argument is not persuasive for reasons set forth above.
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
Prosecution Insights