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 .
Claim Status
Claims 21, 24, 26, 29-30, 33-39 and 42-47 are pending.
Claims 33-39 are withdrawn.
Claims 21, 24, 26, 29-30 and 42-47 are under examination.
Objections to Specification
The objection to the specification due to informalities as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Withdrawn Claim Objections
The objection to claim 24 due to informalities as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Withdrawn Claim Rejections - 35 USC § 112(a)
Written Description
The rejection of claims 29 and 42 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paragraph, as failing to comply with the written description requirement as set forth in the previous office action is withdrawn in view of Applicant’s amendments.
Maintained Claim Rejections - 35 USC § 112(a)
Enablement
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 21, 24, 26, 29-30 and 42-47 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Wands Factors
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some 'experimentation.'” Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
Breadth of the Claims
Instant claims encompass:
recovering “cells that are CD135+ and CD110+” (claim 21 and dependents).
This encompasses cells that are positive for and therefore express both the marker CD135 and the marker CD110.
recovering “cells that are CD135+CD110+APLNR+” (claim 24)
This encompasses cells that are positive for and therefore express all three markers of CD135, CD110 and APLNR.
Direction or Guidance Presented
While contemplating methods comprising recovering CD135+CD110+ cells (pg. 8, 14-15), Applicant provides limited guidance of recovering cells that are CD135+ or CD110+ (Example 2; pg. 40-43)
Present Working Examples
Example 1 (pg. 31-40)
Cells were stained with the antibody hAPJ-APC. Sorting was carried out on a Moflo ASTRIOS Beckman Coulter apparatus and the purity was 98.1% APLNR positive cells. (pg. 33 1st para. “Sorting of APLNR positive cells” ; Figure 4A).
Example 2 (pg. 40-43)
Dissociated EB cells were stained with the antibody CD110-PE (MPL) or CD135- PE (FLT3) then re-stained with PE-MicroBeads (Miltenyi) and finally sorted with the MACS® cell separation device (pg. 40 “Cell Sorting” para.
Absent Working Examples
There is no example provided encompassing recovering cells that are positive for the marker CD135 and are also positive for the marker CD110.
The State of the Prior Art and Unpredictability of the Art
Regarding the cells that are positive for both of the markers CD110 and CD135, the prior art appears to be silent to cells that are positive for both of the markers CD110 and CD135.
Applicant is directed to the art of record of Wang et al. (BD Biosciences; January, 2012; accessed at https://www.bdbiosciences.com/content/dam/bdb/marketing-documents/BD_Multiparametric_Immuno_Stem_Cells_AppNote.pdf), which evidences Expression of CD110 or CD135 during hematopoietic stem cell differentiation. Applicant is directed to Figure 1 of Wang, which is copied below.
PNG
media_image1.png
701
728
media_image1.png
Greyscale
Figure 1 of Wang evidences that CD135 and CD110 appear to be expressed on different progenitor cell types. Specifically, megakaryocyte erythroid progenitor cells (MEPs) express CD110 and are negative for CD135, and granulocyte macrophage progenitor cells (GMPs) are positive only for CD135 (see also Table 1).
Therefore, because instant claims require hematopoietic cells (instant preamble of “preparing a hematopoietic cell graft or enriching a population of cells for hematopoietic stem cells”), because Wang evidences CD110 and CD135 appear to be expressed on different cell types in the hematopoietic lineage, and because the prior art is further silent to populations of hematopoietic cells that express both CD110 and CD135, Applicant is not enabled for recovering cells that are positive for both the marker CD110 and the marker CD135.
Unpredictability of the Art and Quantity of Experimentation Necessary
As the art of Wang demonstrates, CD110 and CD135 appear by the state of the art to be expressed on different cell types, and therefore, recovering cells that are positive for both the marker CD110 and the marker CD135, which are not characterized by the art or Applicant’s specification, would not be an easy task or solely routine experimentation. The type of experimentation required would require new methodologies. This level of experimentation goes beyond what would be routine optimization know at the time of filing. As such, the amount of experimentation would be undue.
The physiological art is recognized as unpredictable (MPEP 2164.03). As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112(a) requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maize!.). In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims, it would have required undue experimentation for one skilled in the art to practice the instant claimed invention.
Enablement - Conclusion
In conclusion, the claims are not enabled because they are drawn recovering a population of CD135+CD110+ cells that not present in the prior art and are not characterized in Applicant’s specification and therefore the methods of recovering these cells are also not characterized in Applicant’s specification or the art. The art at the time of effective filing fail to provide specific guidance that supplement to shortcomings of the specification, and great deal of new methodology would need to be developed to enable the claims and this level of experimentation is undue.
Response to Arguments
Applicant’s arguments, filed 3rd, February , 2026 and 6th, March, 2026, have been fully considered but are not found persuasive.
In the remarks filed 3rd, February , 2026, Applicant argues “Applicants respectfully assert that the claims as filed are enabled; however, Applicants intend to provide evidence substantiating the existence of cells that are CD135+ and CD110+. That evidence will be provided in a supplemental response” (pg. 9).
In the supplemental response, which is the remarks filed 6th, March, 2026, Applicant argues “As discussed in the prior response, Applicants herewith provide evidence substantiating the existence of cells that are CD135+ and CD110+. As described in the attached Declaration by Laurence Guyonneau-Harmand, Ph.D. pursuant to 37 C.F.R. § 1.132, human hematopoietic stem cells stained with fluorescently labeled FLT3+ (CD135+) and MPL + (CD110+) antibodies comprise about 43.53% +/-3.04% of cells analyzed via flow cytometry (see Declaration, pages 2-3 and Figure 1). Therefore, the pending claims are enabled” (pg. 2).
In response, this is not found persuasive. The Declaration under 37 C.F.R. § 1.132 is insufficient to overcome the rejection for the reasons stated below.
As discussed further below, the declaration is not commensurate in scope with instant claims. While the declaration provides evidence that cells that are CD135 and CD110 double positive exist in and can be isolated from cord blood samples, instant claims are drawn to a cell culture method in vitro. Enablement issues remain because the existence of the cells in an ex vivo cord blood sample does not enable a materially distinct method of creating a specific cell type from pluripotent stem cells and subsequently recovering that cell type.
Furthermore, because the CD135 and CD110 double positive cell type did not appear to be known by the state of the art at the time of filing, it would not have been predictable to obtain this not yet known cell type by the culturing method as claimed by Applicant. As set forth above, Applicant provides in Example 2 that cells were stained with the antibody CD110-PE (MPL) or CD135- PE (FLT3), which would result in either CD110 or CD135 positive cells being made and recovered. While it appears from this example that cells that express CD110 or CD135 are made by the present method, Applicant has not shown that cells that express both CD110 and CD135 are made by the present method. Accordingly, because the state of the art evidences that CD110 and CD135 appear to be expressed on different cell types in the hematopoietic lineage, and because the prior art is further silent to populations of hematopoietic cells that express both CD110 and CD135, Applicant is not enabled for making and subsequently recovering cells that are positive for both the marker CD110 and the marker CD135 without a working example or other factually objective evidence on the record that Applicant’s method can arrive making and subsequently recovering this CD110 and CD135 double-positive cell type that did not appear to be known at the time of filing. Because the prior art is silent to populations of hematopoietic cells that express both CD110 and CD135, the prior art is also silent to culture methods that arrive at these double positive cell types, and arriving at these cell types would require undue experimentation.
Response to Declaration under 37 CFR § 1.132
The Declaration under 37 CFR 1.132 filed 6th, March, 2026 is insufficient to overcome the rejection of claims 21, 24, 26, 29-30 and 42-47 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement as set forth in the last Office action because it is not commensurate in scope with instant claims. Specifically, while the declaration provides evidence that cells that are CD135 and CD110 double positive exist in cord blood samples, instant claims are drawn to a cell culture method in vitro. Enablement issues remain because the existence and isolation of the cells in an ex vivo cord blood sample does not enable a materially distinct method of creating a specific cell type from pluripotent stem cells and subsequently recovering those cells that are CD135+ and CD110+. The instantly claimed method requires recovering the cells that are CD135+ and CD110+, and therefore the in vitro culture method must arrive at this cell type for these specific cells to be recovered. Because the state of the art evidences that these markers appeared to be present on different cell types, the state of the art also evidences that obtaining this yet to be known cell type would be unpredictable. Evidence that the claimed CD135+ and CD110+ cells exist in and can be recovered from cord blood is therefore not sufficient to enable the instantly claimed distinct culture method
Examiner’s Remark
To overcome this rejection, it is recommended that Applicant submit factually objective evidence on the record that the method as claimed results in the claimed cells that are CD135+ and CD110+.
Conclusion
THIS ACTION IS MADE FINAL. 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.
No claim is allowable.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANA N EBBINGHAUS whose telephone number is (703)756-4548. The examiner can normally be reached M-F 9:30 AM to 5:30 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/BRIANA N EBBINGHAUS/Examiner, Art Unit 1632
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
Prosecution Insights