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 1-41 have been canceled. Claims 42-61 are pending.
Election/Restrictions
Applicants elected Group III, claims 48-52, without traverse in the reply filed on 10-13-25.
Claims 42-47, 53-61 have been withdrawn.
Claims 48-52 remain 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.
Request for Information under 37 CFR § 1.105
Applicants and the Assignee of this application are required under 37 CFR 1.105 to provide the following information that the examiner has determined is reasonably necessary to the examination of this application:
Pg 133, lines 1-8, teach stem cell-derived neutrophils were “synthesized according to standard techniques”, but the specification does not teach those “standard techniques” or the starting “stem cells” used to derive those neutrophils. Please provide specific protocols for how the “neutrophils” were “derived” from stem cells.
Response
Applicants say pg 21, lines 26-33, teaches differentiating HSCs into neutrophil and point to Exhibits Doulatove, Lieber, Hoi, Lengerke, Timmins. Applicants’ comment does not address the question. Please state whether the protocol on pg 133 started with HSCs. Furthermore, the citation on pg 21 just says the “stem cell is a haematopoietic stem cell”. It does not have a protocol for differentiating HSCs into neutrophils. Furthermore, there are no “Exhibits” of Doulatove, Lieber, Hoi, Lengerke, Timmins attached to the response filed 6-9-26, nor are there citations for the references. The IDSs filed 8-6, 6-29-26, 6-9-26, 3-2-26, 12-4-25, 7-16-25, 3-25-25, 2-12-25, 1-8-25, 4-14-23, 6-13-22 have been reviewed but Exhibits Doulatove, Lieber, Hoi, Lengerke, Timmins cannot be found (Please also consolidate IDSs to streamline the file). Doulatove, Lieber, Hoi, Lengerke, Timmins cannot be considered. It is still unclear how these protocols were used to obtain the neutrophil progenitors in lines 2-3 of claim 48 vs. neutrophils in lines 4-15 of claim 15.
Pg 135, lines 1-12, says proteomics analysis was carried on neutrophils, and pg 134, lines 12-33, describes “Proteomic analysis” for neutrophils and says bioinformatics “was performed using the online DAVID system (Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional” analysis of large gene lists. Nucleic Acids Res. 2009;37:1-13.; and Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4:44-57 (pg 134, lines 29-33). It is still unclear how the DAVID database, Huang, or Huang were used to obtain the neutrophil progenitors in lines 2-3 of claim 48 vs. neutrophils in lines 4-15 of claim 15 because they do not mention neutrophil progenitors, do not teach the common identifier genes for neutrophil progenitors, or teach how to apply the DAVID bioinformatics database to neutrophil progenitors.
Response
Applicants say pg 134, lines 12-33, teaches the “treatment and process for proteomic analysis”. Applicants’ argument is not persuasive. Huang (Nucleic Acids Res., 2009) and Huang (Nat Protoc. 2009) do not teach the common identifier genes for neutrophils or teach how to apply the DAVID bioinformatics database to neutrophils.
Pg 135, line 4, says “low CKA controls” were used to determine proteomic expression patterns, but the specification does not teach what “low” CKAs are or when CKAs are considered “low”.
Response
Pg 67, lines 6-25, describe Fig. 26 which discuss “high CKA neutrophils (80% CKA) compared with low CKA control neutrophils”, and pg 134, lines 9-10, says “cells that demonstrated <51.5% CKA were designated low CKA control neutrophils”. This refers to the ability of the neutrophil to kill specific cancer cells. Thank you for clarifying.
Claim Objections
Claim 48 is missing the fact that the cells are mammalian or isolated. The structures and functions of the neutrophil progenitors claimed can be set forth more clearly, e.g. ---A composition comprising isolated mammalian neutrophil progenitors capable of differentiating into neutrophils that: a) exhibit >51.5% cancer killing activity (CKA) [pg 133, line 10; pg 67, lines 6-25; pg 134, lines 7-10]; b) express increased GM2A, CTSG, CAP37,… … and PSMB2 as compared to neutrophils that exhibit <51.5% CKA; and c) express decreased ANXA1 and PP3CB as compared to neutrophils that exhibit <51.5% (CKA)---.
Claim Rejections - 35 USC § 112
Indefiniteness
Claims 48-52 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.
Withdrawn rejections
The rejection regarding the metes and bounds of “AGE-albumin” in claim 50 has been withdrawn because the term was well-known as evidenced by Son (Scientific Reports, 2016, Vol. 7, No. 11593, pg 1-11).
Pending rejections
The metes and bounds of “neutrophil committed progenitor cells” as newly required in claim 48 cannot be determined. It is unclear how the term “committed” further limits the structures/function of the neutrophil progenitors. It unclear if they can only make neutrophils or if they can be committed to making neutrophils and other cell-types.
The metes and bounds of “neutrophils unsuitable for treating cancer” that “kill less than 51.5% of cancer cells in a cancer kill activity assay” as newly amended in claim 48 does not make sense. The neutrophils kill 48.5% cancer cells, so the term “unsuitable” is inapt.
Lines 2-3 of claim 48 is limited to neutrophil progenitors capable of differentiating into neutrophils, and lines 3-15 describe the structures/functions of the neutrophils. It is unclear how the expression pattern of the neutrophils in lines 3-15 of claim 48 further limits the structure/function of the neutrophil progenitor capable of differentiating into the neutrophil in line 2-3. It is unclear if applicants are attempting to claim neutrophil progenitors that have a specific structure or if applicants are attempting to claim neutrophil progenitors that have been cultured a certain way to imbue the ability to create neutrophils having the features in lines 3-15. For example, since the time of filing Signoretto (Cell. & Mol. Immunol., 2025, Vol. 22, pg 316-329) described “four SSCloLin-CD66b-CD45dimCD34+/CD34dim/-CD64dimCD115 cells as the earliest precursors specifically committed to the neutrophil lineage present in human bone marrow” (abstract). However, applicants have not taught the structure associated with neutrophil progenitors capable of making neutrophils having the structures/functions in lines 4-15 of claim 48. Nor have applicants taught how to culture any neutrophil progenitor to imbue the ability to make neutrophils having the structures/functions in lines 4-15 of claim 48. Therefore, those of skill would not be able to how to use the structures/functions of neutrophils in lines 4-15 of claim 48 to define the structures/functions of the neutrophil progenitors in lines 2-3.
Response to arguments
Applicant point to Example 1 and say “the stem cells (and thus the neutrophil committed progenitor cells of the invention) differentiate into neutrophils” (pg 7 of response). Applicants’ argument is not persuasive for reasons set forth above.
Claim Rejections - 35 USC § 102
A) Claims 48, 50, 52 are rejected under 35 U.S.C. 102a1 as being anticipated by Sweeney (Stem Cells, 2016, Vol. 34, pg 1513-1526).
Sweeney taught human iPS cells in media capable of differentiating into neutrophils (pg 1514, “Materials and Methods”). The neutrophils inherently MUST have the expression pattern in claim 48 as compared to “neutrophils unsuitable for treating cancer” because the iPS cells and neutrophils were “synthesized according to standard techniques” as required on pg 133. The media of Sweeney is the “pharmaceutically acceptable carrier in item b) of claim 48.
Sweeney used G-CSF (pg 1515, col. 1), glutamine (pg 1514, col. 2, 5th full para), IL6 (pg 1514, col. 2, 5th full para), IL3 (pg 1514, col. 2, 6th full para), flt ligand (pg 1514, col. 2, 6th full para), thrombopoietin (pg 1514, col. 2, 6th full para), FBS (pg 1514, col. 2, 5th full para) as required in claim 50.
Sweeney used induced pluripotent stem (iPS) cells as originally required in claim 52 which inherently must become promyelocytes, neutrophilic myelocytes, neutrophilic metamyelocytes, or neutrophilic band cells as required in claim 52.
Response to arguments
Applicants argue Example 1 shows the expression pattern did not result for the differentiation method but from neutrophils having high CKA. Applicants’ argument is not persuasive and irrelevant. Lines 2-3 of claim 48 encompass any neutrophil progenitor. While lines 4-15 of claim 48 define neutrophils derived from those progenitors, the protocol of Sweeney most certainly results in neutrophil progenitors capable of differentiating into neutrophils having the structures/functions in lines 4-15 because the iPS cells and neutrophils were “synthesized according to standard techniques” as required by applicants on pg 133. There is nothing special about the structure of the neutrophil progenitors themselves in claim 48 that distinguish them from those that must have occurred in Sweeney. Original claim 52 says the progenitor may be an iPS cell as described by Sweeney. Therefore, the process of Sweeney must result in neutrophil progenitors (lines 2-3 of claim 48) capable of differentiating into neutrophils having the structures/functions set forth in lines 4-15 of claim 48.
B) Claims 48-52 are rejected under 35 U.S.C. 102a1 as being anticipated by Saito (Int J Hematol, 2008, Vol. 88, pg 64-72).
Saito taught human CD34+ cells isolated from peripheral blood in media (pg 64, abstract; pg 65, “Cell Preparations”) capable of differentiating into neutrophils (pg 56, col. 2, 2nd full paragraph, last sentence) and neutrophil progenitors (pg 67, section 3.3).
Lines 2-3 of claim 48 encompass any neutrophil progenitor. While lines 4-15 of claim 48 define neutrophils derived from those progenitors, the protocol of Saito most certainly results in neutrophil progenitors capable of differentiating into neutrophils having the structures/functions in lines 4-15 because the iPS cells and neutrophils were “synthesized according to standard techniques” as required by applicants on pg 133. There is nothing special about the structure of the neutrophil progenitors themselves in claim 48 that distinguish them from those that must have occurred in Saito. Original claim 52 says the progenitor may be an HSC as described by Saito. Therefore, the process of Saito must result in neutrophil progenitors (lines 2-3 of claim 48) capable of differentiating into neutrophils having the structures/functions set forth in lines 4-15 of claim 48.
The media of Saito is the “pharmaceutically acceptable carrier in item b) of claim 48.
Saito cultured the CD34+ cells with TNFα as required in claim 49 (pg 66, col. 2, Section 3.1) as required in claim 49
Saito used GM-CSF (pg 71, last para), G-CSF (pg 66, col. 2, Section 3.1), IL3 (pg 65, Section 2.2), IL4 (pg 71, last para), TNFα (pg 66, col. 2, Section 3.1), FLT ligand (pg 71, last para), fetal bovine serum (pg 76, section 2.1) as required in claim 50.
Saito used GM-CSF and INFα together (pg 71, last para) as required in claim 51
The CD34+ cells of Saito MUST inherently differentiate into promyelocytes, neutrophilic myelocytes, neutrophilic metamyelocytes, or neutrophilic band cells as required in claim 52 before becoming neutrophils.
Response to arguments
Applicants argue Saito did not characterize neutrophil progenitors. Applicants’ argument is not persuasive. Lines 2-3 of claim 48 encompass any neutrophil progenitor. While lines 4-15 of claim 48 define neutrophils derived from those progenitors, the protocol of Saito most certainly results in neutrophil progenitors capable of differentiating into neutrophils having the structures/functions in lines 4-15 because the iPS cells and neutrophils were “synthesized according to standard techniques” as required by applicants on pg 133. There is nothing special about the structure of the neutrophil progenitors themselves in claim 48 that distinguishes them from those that must have occurred in Saito. Original claim 52 says the progenitor may be an HSC as described by Saito. Therefore, the process of Saito must result in neutrophil progenitors (lines 2-3 of claim 48) capable of differentiating into neutrophils having the structures/functions set forth in lines 4-15 of claim 48.
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
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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