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 .
Duplicate Claim Warning
Applicant is advised that should claim 2 be found allowable, claim 12 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 16, 2026 has been entered.
Status of the Claims
Claims 1-8 and 10-12 were pending. Claims 2-8 and claims 10-11 are amended. Claim 1 is canceled.
Claims 2-8 and 10-12 are examined herein.
Withdrawn Rejections
The objections to claim 1 are withdrawn in view of claim cancellation.
The objections to claims 2-7 are withdrawn in view of claims amendments.
The rejections of claim 1 are withdrawn in view of claim cancellation.
The rejection of claims 3 and 5-8 under 35 U.S.C. §102 is withdrawn in view of claims amendments.
The rejection of claims 4 and 10 under 35 U.S.C. §103 is withdrawn in view of claims amendments.
Claim Interpretation
The preamble of claim 11 recites a kit for detecting differentiated hematopoietic cells using the method of claim 2. The normal purpose of a claim preamble is to recite the purpose or intended use of the claimed invention. Such statements merely define the context in which the invention operates and usually will not limit the scope of the claim (MPEP 2111.02 and DeGeorge v. Bernier, Fed. Cir. 1985, 226 USPQ 758, 761 n.3).
In the instant case, the statement in the preamble does not provide antecedent basis for terms in the body of the claim, and is not essential to understand the limitations or terms in the body of the claim. The claim does not include, for example, any kit component that is exclusively required for detecting hematopoietic cells in their differentiated state. Rather, the body of the claim only states that the kit components comprise “at least one growth factor for proliferating isolated hematopoietic stem cells into cell colonies” without any requirement for detecting differentiated cells. Similarly, the limitation of a marker cocktail is not required exclusively for detecting differentiated cells.
The preamble of claim 11 reciting a kit for detecting differentiated hematopoietic cells using the method of claim 2 will be interpreted as an intended use of the kit.
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 2-8 and 10-12 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.
Claims 2 and 12 are directed to methods of characterization of differentiated hematopoietic stem cells using CD14, CD15, and CD235a specific conjugates comprising:
a) Providing a cell sample comprising undifferentiated hematopoietic stem cells;
b) Seeding cells of said cell sample in groups of 1 - 1000 cells/well;
c) Contacting the cell colonies with a marker cocktail comprising at least 3 different
marker conjugates each comprising at least one antigen recognizing moiety against
CD14, CD235a and CD15 and each comprising at least one detection moiety;
d) Measuring a relative amount of differentiated hematopoietic stem cells in a
cell colony labelled with the marker conjugates by measuring the presence of
CD14, CD15, and CD235a; and
e) Determining a differentiation status of stem cells in a cell sample based on the relative
expression levels of CD14, CD15, and CD235a measured in step d.
Nature of the invention – the invention is directed to using labeled conjugates against CD14, CD15, and CD235a markers to stain differentiated hematopoietic stem cell colony in order to identify the colony as one of BFU-E, CFU-G, CFU-M, CFU-GM, or CFU-GEMM based on relative expression levels of CD14, CD15, and CD235a markers.
The specification discloses the relative expression levels of CD14, CD15, and CD235a markers for BFU-E, CFU-G, CFU-M, CFU-GM, and CFU-GEMM colonies ([0031]), growth of human BFU-E, CFU-E, CFU-G, CFU-M, CPU-GM and CFU-GEMM colonies ([0039]-[0041]), preparation of HSC-CFU assay media ([0042]), preparation of cell samples ([0043]-[0044]), performing HSC-CFU assay and flow cytometric analysis ([0045]-[0046]).
Additionally, the specification discloses HSC-CFU assay according to the prior art ([0047]-[0051]).
Finally, the specification discloses the relative expression levels of CD14, CD15, and CD235a markers corresponding to BFU-E, CFU-G, CFU-M, CFU-GM, or CFU-GEMM colonies ([0052]-[0061]).
State of the prior art & level of predictability in the art.
The prior art is silent on using relative expression levels of CD14, CD15, and CD235a markers for identification of BFU-E, CFU-G, CFU-M, CFU-GM, or CFU-GEMM colonies. The level of predictability in the art of biomarkers is low and an ordinary practitioner cannot use results from other biomarkers to determine the relative expression levels of CD14, CD15, and CD235a markers.
Level of one of ordinary skill – the related skill level is high with an ordinary practitioner possessing a PhD and related post-doctoral research experience.
Amount of direction and examples provided by the inventor.
The inventors disclose using relative expression levels of CD14, CD15, and CD235a markers for identification of BFU-E, CFU-G, CFU-M, CFU-GM, or CFU-GEMM colonies. However, the disclosed relative expression levels were obtained using flow cytometry of BFU-E, CFU-E, CFU-G, CFU-M, CPU-GM and CFU-GEMM colonies, wherein the colonies were identified using unreliable HSC-CFU assay according to the prior art ([0047]-[0051]) with statistically unreliable results (high p-values, [0050]).
The unreliable identification of the BFU-E, CFU-G, CFU-M, CFU-GM, or CFU-GEMM colonies is demonstrated by the inventors in Fig. 3b, wherein researchers attempted to identify 27 colonies. In inventors’ own words “Fig. 3b shows the results obtained from the six independent researchers manifesting the high degree of variability observed after visual inspection. These findings strongly suggest that morphological and phenotypic classification is neither robust nor reproducible” ([0017]). For example, colony #4 was identified as CFU-GM, CFU-G, BFU-E, and CFU-M; and colony #8 was identified as CFU-GM, CFU-G, and CFU-M.
The specification is silent with respect to how the inventors were able to reliably identify BFU-E, CFU-E, CFU-G, CFU-M, CPU-GM and CFU-GEMM colonies. The only available identification method “morphological and phenotypic classification is neither robust nor reproducible”.
With the underlying colony identification method being unreliable, the specification needs to provide more evidence to ensure that the measured relative expression levels of CD14, CD15, and CD235a markers indeed corresponded to correct kinds of colonies. For example, the disclosed data were not confirmed in experiments with BFU-E, CFU-E, CFU-G, CFU-M, CPU-GM and CFU-GEMM cells originating from reliable, reference cultures.
As such, the disclosed methods can be called reproducible, automated, and user-independent CFU assays, but since the methods are not based on reliably identified original BFU-E, CFU-E, CFU-G, CFU-M, CPU-GM and CFU-GEMM colonies, these methods cannot be used for reliable identification of unknown colonies.
In order to establish relative expression levels of CD14, CD15, and CD235a markers Applicant needs to demonstrate that these levels were measured on reliably identified BFU-E, CFU-E, CFU-G, CFU-M, CPU-GM and CFU-GEMM colonies.
Claims 3-8 and 10-11 are rejected to as being dependent upon rejected base claim 2.
Therefore, based on the above findings, one of ordinary skill in the art would conclude that Applicant did not have possession of the claimed invention.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-8 and 10-12 are 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.
Claim 2 recites “a cell sample” (steps a and e). Line 1 already recites “a cell sample”. It is unclear if the claim is referring to an additional cell sample or the cell sample already recited in the claim.
Claim 2 recites “contacting the cell colonies” (step c). There is insufficient antecedent basis for “the cell colonies”.
Claim 2 recites “measuring the presence of CD14, CD15, and CD235a” in step (d) and “the relative expression levels of CD14, CD15, and CD235a measured in step d” in step (e). It is unclear what is actually measured in step (d): the presence of the biomarkers, which is a qualitative result (present or not present) or the relative expression levels of the biomarkers, which is a quantitative result. One cannot calculate the relative expression levels (step (e)) from the qualitative results of step (d).
Claim 2 recites “a cell colony” twice. It is unclear if the claim is referring to a different cell colony or the cell colony already recited in the claim.
Claim 2 recites “a marker cocktail comprising at least 3 different marker conjugates each comprising at least one antigen recognizing moiety against CD14, CD235a and CD15” (step c). It is unclear if the “at least one antigen recognizing moiety” is specific against all three molecules: CD14, CD235a and CD15, or only one of them. The claim is interpreted as a marker cocktail comprising at least 3 different marker conjugates each comprising at least one antigen recognizing moiety against CD14, CD235a or CD15, with each conjugate targeting a different antigen molecule.
Claims 2 and 12 recite “detecting differentiated hematopoietic cells in a cell sample” (line 1) and “a cell sample comprising undifferentiated hematopoietic stem cells” (line 3). It is unclear what kind of cells the cell sample comprises: differentiated or undifferentiated.
Claims 2 and 12 recite “based on the relative expression levels of cells labelled with the marker conjugates specific for CD14, CD15, and CD235a”. “Relative expression levels of cells” is not art recognized term. The term “expression” cannot be applied to cells, but it can be applied to biomarkers expressed on cell surface. The claims are interpreted as a relative fraction of cells labelled with the marker conjugates specific for CD14, CD15, and CD235a.
Claims 3-8 and 10-11 are rejected to as being dependent upon rejected base claim 2.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Wognum (IDS; PGPub 2007/0059778).
Regarding claim 11, Wognum teaches colony forming cell (CFC) assays applicable to hematopoietic CFC assays (Abstract) comprising BFU-E, CFU-G, CFU-M, CFU-GM, and CFU-GEMM cells ([0005]). Specifically, Wognum teaches a method comprising:
providing a cell sample comprising hematopoietic stem cells - specifically, Wognum teaches culturing a cell preparation in a culture medium suitable to promote the growth and differentiation of the progenitor cells into colonies containing a specific cell type [0021], therefore, Wognum inherently teaches providing a cell sample;
contacting the cell colonies with marker conjugates comprising at least one detection moiety – specifically, Wognum teaches adding a detection reagent that can detect the progenitor cells or the specific cell type ([0022]). “The invention comprises adding a detection reagent, most likely a fluorescently labeled antibody, that is specific for antigens” (Abstract); and
measuring a relative amount of differentiated hematopoietic stem cells in a cell colony labelled with the marker conjugates – specifically, detecting progenitor cells or the specific cell type ([0023]).
Regarding marker conjugates comprising antigen recognizing moieties against CD14, CD235a, and CD15, Wognum teaches that erythroid colonies can be stained with a FITC-conjugated antibody against Glycophorin-A (another name for CD235a) ([0066]), monocytes can be selectively stained with antibodies against CD14, and granulocytes can be selectively stained with antibodies against CD15 ([0050]).
Regarding specific markers, Wognum teaches that:
erythroid colonies can be stained with an antibody against Glycophorin-A (CD235a) ([0066]). “E” in CFU-GEMM stands for erythrocyte and erythrocyte is an erythroid cell type. Therefore, CFU-GEMM cells can be detected using CD235a marker;
monocytes can be selectively stained with antibodies against CD14 ([0050]). “M” in CFU-GEMM stands for monocyte. Therefore, CFU-GEMM cells can be detected using CD14 marker;
granulocytes can be selectively stained with antibodies against CD15 ([0050]). “G” in CFU-GEMM stands for granulocyte. Therefore, CFU-GEMM cells can be detected using CD15 marker;
Therefore, CFU-GEMM cells are CD15+, CD14+, and CD235a+.
Wognum does not specifically teach a kit for detecting differentiated hematopoietic cells using the method of claim 2, comprising: a) cell medium with at least one growth factor for proliferating isolated hematopoietic stem cells into cell colonies and b) a marker cocktail comprising one more marker conjugates, each conjugate comprising at least one detection moiety and at least one antigen recognizing moiety specific for CD14, CD235a and or CD15.
However, in a separate embodiment, Wognum teaches marker conjugates comprising at least one antigen recognizing moiety (antibodies, Abstract) and at least one detection moiety (a fluorescent label, Abstract).
Additionally, Wognum teaches culturing the cell preparation in a culture medium suitable to promote the growth and differentiation of the progenitor cells into colonies containing a specific cell type ([0021]). Invention also comprises modifications to the culture medium to selectively promote the development of one colony type (Abstract) and using different cytokines such as GM-colony stimulating factor, IL-3, IL-6, G-CSF, and Stem Cell Factor ([0005]);
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Wognum by combining the cell media with at least one growth factor and a marker cocktail comprising marker conjugates each comprising at least one detection moiety and at least one antigen recognizing moiety against CD14, CD235a and CD15 as taught by Wognum, in order to make a kit for “CFC assay that enable analysis of temporal, real-time changes in antigen expression during colony development” (Abstract), as an obvious matter of combining prior art elements according to known methods to yield predictable results. Organizing several reagents as a kit is well-known in the art and widely used because of convenience.
One having ordinary skill in the art would have had a reasonable expectation of success in combining the prior art references because the individual components when combined in the kit would still perform their corresponding functions, and the combination would not produce a ‘new’ or ‘different function’: the marker conjugates would bind and detect their markers; the cell media would support growth of the cells; and the growth factor would stimulate growth of a selected cell type.
Although Wognum does not specifically teach the kit for using the method of claim 2, such limitation is drawn to intended use of the kit and therefore the prior art only needs to be capable of performing the recited intended use. So long as the marker conjugates in the kit of Wognum are capable of being used with the method of claim 2, they read on the claims.
Response to Arguments
Applicant’s arguments filed March 16, 2026 have been fully considered.
Applicant argues that “Claim 1 has been canceled, and thus this rejection is moot” (pg. 7, last par.). The argument is persuasive; therefore, the rejection of claim 1 is withdrawn.
Applicant argues that “Claims 2-8 are amended to depend from claim 2, and are patentable by their dependence from claim 2 as well as for the additional features it recites (pg. 7, last par.). The argument is persuasive; therefore, the rejection of claims 3-8 under 102 and 103 is withdrawn.
Applicant respectfully requests that the rejection of claims 2-8 and 10-12 are rejected under 35 U.S.C. 112(b) be withdrawn (pg. 8, par.1). The argument is not persuasive because amended claim 2 contains subject matter of cancelled claim 1 and therefore inherits its rejections. Please, see 112(b) rejection above for details.
Claims 1, 3, and 5-8 were rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102 (a)(2) as being anticipated by Wognum. Applicant argues that “Claim 1 has been canceled, and thus this rejection is moot. Claims 3 and 5-8 are amended to depend from claim 2, and are patentable by their dependence from claim 2 as well as for the additional features it recites” (pg. 8, par. 2). The argument is persuasive; therefore, the rejection of claims 3 and 5-8 under 102 is withdrawn.
Claim 4 was rejected under 35 U.S.C. 103 as being unpatentable over Wognum in view of Perry. Applicant argues that “Claim 4 is amended to depend from claim 2, and is patentable by its dependence from claim 2 as well as for the additional features it recites” (pg. 8, par. 3).
Claim 10 was rejected under 35 U.S.C. 103 as being unpatentable over Wognum. Applicant argues that “Claim 10 is amended to depend from claim 2, and is patentable by its dependence from claim 2 as well as for the additional features it recites” (pg. 8, par. 4).
The arguments are persuasive; therefore, the rejection of claims 4 and 10 under 103 is withdrawn.
Claim 11 was rejected under 35 U.S.C. 103 as being unpatentable over Wognum. Applicant argues that “Claim 11 is amended to depend from claim 2, and is patentable by its dependence from claim 2 as well as for the additional features it recites” (pg. 8, par. 5). The argument is not persuasive because claim 11 recites a kit, and its use in the method of claim 2 is intended use (please, see rejection above for details).
Applicant argues that since claims 2 and 12 were indicated as free of the art they are “patentable save for the enablement rejection under 35 USC 112(b)” (pg. 8, par. 6). The argument is not persuasive because: (a) there was no enablement rejection of claims 2 and 12 under 35 USC l 12(b) and (b) being free of the prior art does not necessarily mean that the claims are free of other rejections - claims 2 and 12 are still rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement and under 35 U.S.C. 112(b) (see above for details).
Claims 2 and 12 were rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. Applicant disagrees and provides a summary of the invention and additional arguments (pg. 8, last par. - pg. 14).
Specifically, Applicant argues about the rejection of claims 2 and 12 under 35 U.S.C. 112(a) presented in final OA (mailed November 18, 2025), on pg. 3, par. 3 (Remarks, pg. 10, last 2 par. - pg. 13, par. 6) and (the Declaration, pg. 2, par. 1 – pg. 5, Fig. 5).
Applicant's arguments are persuasive and the rejection of claims 2 and 12 under 112(a) is withdrawn, but only to the extent of the first 112(a) rejection stating: "Claims 2 and 12 recite relative amounts of three markers used for identification of the differentiated cells. Fig. 3 legend discloses that there were other antigens detected in the same experiment - "The difference to 100% relates to other antigens which are not of interest for the method of the invention" ([0031]). The specification fails to disclose contribution of other markers to the total count. In the absence of the count for the other markers/ antigens the disclosed relative amounts make the recited quantitative limitations not defined. Therefore, the actual percent values in claims 2 and 12 lack support from the disclosure" (final OA, November 18, 2025; pg. 3, par. 3).
Applicant argues about the second rejection of claims 2 and 12 under 35 U.S.C. 112(a) (pg. 3, par. 4 of 112(a) rejection, final OA, November 18, 2025) as failing to comply with the written description requirement (Remarks, pg. 10, par. 2 and pg. 13, last par. - pg. 14).
The arguments are not persuasive because Applicant fails to point out in the specification how the studied cell colonies were reliably identified as CFU-GEMM, CFU-M, CFU-GM, BFU-E, and CFU-G differentiated hematopoietic cell colonies. The entire invention disclosing specific levels for CD14, CD15, and CD235a markers present in each kind of cell colonies hinges on the reliability of this original identification (please see 112(a) rejection above for more details).
In the argument Applicant reiterates the current error prone nature of the CFU assays “standard so called CFU assays are based on the subjective visual evaluation of cell colonies in a dish. Such a method is error prone, because it relies among other things on the experience and training of the team member. Moreover sometimes the colony types are hard to distinguish. So the result of the assay may vary depending on the Team member who is analyzing the dish. This is for example shown in Figure 3b page 20. Here the same CFU assay (same dish) was evaluated by 6 different persons. The results differ from person to person” (Remarks, pg. 13, last par.). The Declaration also confirms lack of any reference cell materials used in the experiments (Declaration, pg. 2, par. 2).
Applicant states “the disclosed method is a standardized method because it does not rely on the experience of different persons. Every person will get the same result if the same sample is analyzed. This is because the invented method is based on cell surface marker analysis, which is done by e.g. a FACS machine. Visual subjective evaluation of the colonies is therefore not necessary” (Remarks, pg. 14, par. 1).
This statement and the specification still fail to demonstrate evidence of how Applicant was able to use FACS to standardize the method when Applicant confirmed in the preceding paragraph that “the result of the assay may vary depending on the Team member who is analyzing the dish” and “results differ from person to person” (pg. 13, last par.). The method did not use any standard or reference cell culture.
In order to use FACS to obtain specific levels for CD14, CD15, and CD235a markers for each of CFU-GEMM, CFU-M, CFU-GM, BFU-E, and CFU-G differentiated hematopoietic cell colonies, one would need to have reliable identification of the differentiated hematopoietic cell colonies, which in Applicant’s own words could not be done reliably (pg. 13, last par.). This is a chicken-and-egg-like dilemma – without reliable identification of the differentiated hematopoietic cell colonies Applicant could not use FACS to reliably measure expression levels for CD14, CD15, and CD235a markers for each kind of hematopoietic cell colonies. The FACS method makes analysis less prone to human error, but the use of FACS does not make determination of CFU-GEMM, CFU-M, CFU-GM, BFU-E, and CFU-G differentiated hematopoietic cell colonies any more reliable than the prior art method disclosed in the specification ([0047]-[0051]) because the original determination of CFU-GEMM, CFU-M, CFU-GM, BFU-E, and CFU-G differentiated hematopoietic cell colonies for FACS analysis was performed using the same error prone prior art method.
The specification, the current argument, and the Declaration by Dr. Ute Bissels fail to provide evidence that Applicant was in possession of reliably identified differentiated hematopoietic cell colonies. The argument of Dr. Ute Bissels that “The claimed method is standardizable in terms of user independence” (Declaration, pg. 5, last par.) is persuasive only to the extent of excluding variability caused by individual scientists and getting better %CV due to using FACS instruments. The argument still fails to provide evidence for reliable identification of the original colonies. Therefore, subsequent assignment of the specific expression levels for CD14, CD15, and CD235a markers for each of the CFU-GEMM, CFU-M, CFU-GM, BFU-E, and CFU-G differentiated hematopoietic cell colonies lacks certainty.
Applicant argues that “With respect to item 4) above, Applicant respectfully disagrees. Cells can and do express cell surface markers. This is well established and accepted in the field” (pg. 14, par. 3). The argument is not persuasive because Applicant argues about expression of cell surface markers by cells, but not the limitation of “relative expression levels of cells” rejected under 112(b).
As presented in 112(b) above: “Relative expression levels of cells” is not art recognized term. The term “expression” cannot be applied to cells, but it can be applied to biomarkers expressed on cell surface. The claims are interpreted as a relative fraction of cells labelled with the marker conjugates specific for CD14, CD15, and CD235a.
Subject Matter Free of the Prior Art
Claims 2-8, 10, and 12 are free of the prior art.
Prior art references are silent on using CD235a, CD15, and CD14 biomarkers as a panel for identification of differentiated hematopoietic cells: CFU-GEMM, CFU-M, CFU-GM, BFU-E, CFU-G.
The closest prior art:
Brown et al. (WO 2010141801) teach using monoclonal antibodies to CD34, CD45, CD43, CD31, CD41 and CD235a in hematopoietic clonogenic assays ([0036]), but fail to teach the use of CD15 and CD14 biomarkers as a part of the panel.
Hariri et al. (WO 03087392) teach using biomarkers CD15, CD34, CD33, CD133, or CD54 (pg. 27, par. 3), but fail to teach the use of CD235a and CD14 biomarkers as a part of the panel.
Delaney et al. (WO-2018140532) teach CD7, CD14, CD15, CD19 and CD56 marker expression determined by flow cytometry ([0025]), but fail to teach the use of CD235a biomarker as a part of the panel.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
/ALEXANDER ALEXANDROVIC VOLKOV/
Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677