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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Status of Claims
Claims 1, 4, 7, 10-13, and 46-54 are currently pending. Claims 1, 4, 7, 10-13 and 48 have been amended by Applicants’ amendment filed 07-27-2026. Claims 4, 5, 9 and 14-26 have been canceled by Applicants’ amendment filed 07-27-2026. Claims 49-54 have been added by Applicants’ amendment filed 07-27-2026.
Applicant's election of Group I, claims 1-13, directed to a method for selecting one or more human hematopoietic stem/progenitor cells from within a heterogenous population of lin- HSPCs; and the election of Species of:
Species (A): wherein the method of claim 1 further comprising the step of selecting for CD34+ cells (claim 3); and
Species (B): wherein the selecting for the one or more of sLeXhigh cells comprises selecting for cells having the highest 10% of sLeX expression level within the heterogenous population (claim 11); in the reply filed September 24, 2024 was previously acknowledged.
Regarding newly submitted claims 51-54, the claims are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Newly submitted claim 51 is directed to a method for selecting and separating a subpopulation of cells from within a heterogenous population of CD34+ HSPCs that express sialylated Lewis X (sLeX), comprising: contacting the heterogenous population of CD34+ HSPCs with a binding molecule for sLeX, measuring the level of sLeX expression, selecting the subpopulation of cells that express sLeX that exceed sLeX expression by at least 85%, and separating the selected subpopulation (claim 51). Newly submitted claim 54 is directed to a method for selecting and separating a subpopulation of cells from within a heterogenous population of CD34+ HSPCs that express sialylated Lewis X (sLeX), comprising: contacting the heterogenous population of CD34+ HSPCs with a binding molecule for sLeX, measuring the level of sLeX expression, selecting the subpopulation of cells that express sLeX that exceed sLeX expression by at least 85%, and separating the selected subpopulation (claim 54). Claim 1 of the claims filed February 29, 2024 was directed to a method for selecting one or more HSPCs from within a heterogenous population of lin- HSPCs, comprising the steps of contacting, measuring the amount of sLeX present on individual cells, and selecting for one or more sLeXhigh cells (clam 1). Thus, newly submitted claims 51 and 54 require a search and examination beyond the claims as originally presented, and constructively elected. The different species of methods and/or compositions would require a different field of search; the prior art applicable to one species would not likely be applicable to another species; and/or the species are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112(a). For example, the limitations of newly submitted claims 51 and 54 recite an independent and distinct process steps as compared to the elected invention of instant claim 1 of the claims filed February 29, 2024.
As noted in MPEP 818.02(a), wherein subsequently presented claims to an invention other than that acted upon should be treated as provided in MPEP § 821.03. As recited in MPEP 821.04 (¶ 8.04), since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits.
Accordingly, newly submitted claims 51-54 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
Claims 14-26, 46 and 48 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 2, 4, 5, 6, 10, 12, 13 and 47 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
Although Applicant indicated that the election was made with traverse, Applicant failed to provide any argument or remarks with regard to a traversal. Thus, because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election of invention has been treated as an election without traverse (MPEP § 818.03(a)).
The restriction requirement was deemed proper and was made FINAL.
The claims will be examined insofar as they read on the elected species.
A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
Therefore, claims 1, 7, 11, 49 and 50 are under consideration to which the following grounds of rejection are applicable.
Interview Summary
Applicant contacted the Examiner to set up an interview, where such telephonic interview was conducted between the Examiner and Applicant’s representative Ethan Fitzpatrick on July 24, 2026, where potential amendments to the claims were discussed.
Declaration
The Examiner previously acknowledged receipt of an executed Declaration under 37 C.F.R. § 1.132 signed by Joseph Lau on May 26, 2026 (hereinafter the “Lau decl.”); and filed on May 26, 2026.
The Lau decl. has been considered by the Examiner.
Priority
The instant application filed February 29, 2024 is a CON of PCT/US2024/011599, filed January 16, 2024 (now abandoned), which claims priority to US Provisional Patent Application 63479853, filed
January 13, 2023.
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application including the as-filed Specification and original claims filed February 29, 2024; as well as, US Provisional Patent Application 63/479,853, filed January 13, 2023, fail to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The specific method steps recited in independent claim 1 does not have support for; “collecting a subpopulation consisting essentially of cells that natively express sLeX at a level that exceeds 85% of the sLeX expression level of the cells measured in step (2)”. Therefore, the priority date for the presently claimed invention is February 29, 2024, the filing date of US Patent Application 18591921, filed February 29, 2024.
Applicants are invited to specifically indicate the location of the cited phrases pertinent to claim 1 of the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 27, 2026 has been considered. An initialed copy of the IDS accompanies this Office Action.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed July 27, 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below are herein withdrawn.
Claim Rejections - 35 USC § 102
The rejection of claims 1, 7 and 11 is withdrawn under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Karakantza et. al. (hereinafter “Karakantza”) (British Journal of Haematology, 1994, 86, 883-886).
Karakantza does not specifically exemplify collecting a subpopulation consisting essentially of cells natively expressing >85% of sLeX.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
(2) The rejection of claims 1, 7 and 11 is withdrawn under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Bissels et. al. (hereinafter “Bissels”) (US Patent Application Publication 20220276247, published September 1, 2022; International Application WO2021013669, filed July 16, 2020; and effective filing date EP 19188003.8, July 24, 2019).
Bissels does not specifically exemplify a subpopulation consisting essentially of cells natively expressing >85% of sLeX.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
The rejection of claims 1, 7 and 11 is withdrawn under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Cohen et. al. (hereinafter “Cohen”) (Breast Cancer Research and Treatment, 2019, 176, 545-556).
Cohen does not specifically exemplify collecting a subpopulation consisting essentially of CD34+ human HSPCs.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
Maintained Objections/Rejections
Claim Rejections – 35 USC § 112(b)
The rejection of claims 1, 7, 11, 49 and 50 is maintained under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards
as the invention.
Claim 1 is indefinite for the recitation of the term “at the native level of expression” and “sLeX natively expressed” such as recited in claim 1, lines 4 and 8. There is insufficient antecedent basis for the term “the native level of expression” in the claim. Moreover, it is unclear what native level of expression is being referred to including whether it is a native level measured in a healthy human patient (male or female); a patient with breast cancer; a patient with respiratory disease, any mammal; and/or whether the term refers to some other native level of expression and, thus, the metes and bounds of the claim cannot be determined. The Examiner suggests that Applicant amend the claim to recite, for example, “a heterogenous population of CD34+ human HSPCs in a healthy human, wherein the surface of healthy human HSCs express a native level of sLeX.”
Claim 1 is indefinite for the recitation of the term “the level of expression” such as recited in claim 1, line 8. There is insufficient antecedent basis for the term “the level of expression” in the claim.
Claims 1, 11, 49 and 50 are indefinite for the recitation of the term “step (X)” such as recited in claim 1, lines 10 and 13. There is insufficient antecedent basis for the term “step (X)” in the claim because claim 1, line 5 recites the term “the steps of (1)…(2)…and (3)” Moreover, claims 11, 49 and 50 depend from instant claim 1, wherein claim 1, line 10 recites “the steps of: (1)…(2)…and (3)” and, thus, the metes and bounds of the claim cannot be determined.
Claim 1 is indefinite for the recitation of the term “collecting a subpopulation consisting essentially of cells” such as recited in claim 1, line 11 because it is unclear what “subpopulation” is being collected and, therefore, what subpopulation consists essentially of cells that natively express sLeX. It is unclear whether the “subpopulation” is a subpopulation of CD34+ human HSPCs, a subpopulation of HSPCs, a subpopulation of individual cells bound to a binding molecule, cells, etc. and, thus, the metes and bounds of the claim cannot be determined.
Claims 1, 11, 49 and 50 are indefinite for the recitation of the term “consisting essentially of… the sLeX expression level of the cells measured in step (2)” or “consists essentially of cells…measured in step (2) such as recited in claim 1, lines 11-12 because the as-filed Specification and/or the original claims do not recite that subpopulation consisting essentially of… of the sLeX expression level of the cells measured in step (2) is collected and, thus, the metes and bounds of the claim cannot be determined.
Claims 1, 11, 49 and 50 is indefinite for the recitation of the term “the sLeX expression level” such as recited in claim 1, line 12. There is insufficient antecedent basis for the term “the sLeX expression level” in the claim.
Claims 1, 11, 49 and 50 is indefinite for the recitation of the term “the cells” such as recited in claim 1, lines 12-13. There is insufficient antecedent basis for the term “the cells” in the claim because claim 1, lines 1-2, 9 and 11 recite terms such as: a subpopulation of cells, individual cells within the heterogenous population of CD34+ human HSPCs, and a subpopulation of cells that natively express sLeX.
Claims 11, 49 and 50 are indefinite for the recitation of the term “the collected subpopulation” such as recited in claim 11, line 2. There is insufficient antecedent basis for the term “the collected subpopulation” because claim 1, line 11 recites the term “collecting a subpopulation.” Moreover, claims 11, 49 and 50 depend from instant claim 1, such that it is unclear what subpopulation is collected (e.g., collecting a subpopulation of CD34+ human HSPCs, a subpopulation of individual cells bound to a binding molecule, etc.) and, thus, the metes and bounds of the claim cannot be determined.
Claim 7 is indefinite insofar as it ultimately depends from instant claim 1.
New Objections/Rejections
Claim Rejections - 35 USC § 112(a) – New Matter
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 1, 7, 11, 49 and 50 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection. This is a new rejection necessitated by amendment of the claims in the response filed 07-27-2026.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims” and “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117”.
The claim contains subject matter that was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art (hereafter the Artisan), that the inventor(s), at the time the application was filed, had possession of the claimed invention. 37 CFR §1.118 (a) states that "No amendment shall introduce new matter into the disclosure of an application after the filing date of the application". Claim 16 recites (in part): “collecting a subpopulation consisting essentially of cells that natively express sLeX at a level that exceeds 85% of the sLeX expression level of the cells measured in step (2) to enrich for HSCs from the heterogenous population of CD34+ human HSPCs” in lines 11-14. However, support was not found for these limitations in the as-filed Specification and/or the original claims.
Upon review of the instant as-filed Specification and original claims, support was not found for collection of a subpopulation consisting essentially of cells that natively express sLeX as recited in instant claim 1. Applicant pointed to paragraphs [0050] for support of the phrase. The instant as-filed Specification, filed February 29, 2024 teaches, for example: “the heterogenous population of lin- human HSPCs expressing sLeX at density levels within the lower 85% of the range of sLeX expression within the heterogenous cell population” (paragraph [0016]); “the selection comprises one or more negative selection steps to enrich a population of sLeX10w/- cells by depletion of cells expressing sLeX at cell density levels >85% of the level within the heterogenous cell population. In some embodiments, the sLeX10w/- cells are the cells having the lowest 10% of sLeX expression level in the heterogenous population of nucleated cells” (paragraph [0020]); "sLeXhigh" cells refers to cells that express sialylated Lewis X (sLeX) at a level that is greater than at least 85% of the cells that express sLeX within that population of HSPCs; i.e., the cells harbor sLeX surface density above the 85th percentile of the sLeX surface density (expression level) within the cells of the population” (paragraph [0050]); and “Glycan modification according to this method results in cells according to the present disclosure that have at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more viability at 24 hours or more after treatment” (paragraph [0089]). No such corresponding teaching of collecting a subpopulation consisting essentially of cells that natively express sLeX at a level that exceeds 85% of the sLeX expression level of the cells measured in step (2) as recited in instant claim 1 is taught by the instant as-filed Specification and/or the original claims.
A claim-by-claim analysis and for independent claim 1, and a method step by method step analysis regarding where support can be found for the composition found in each of the plurality of microcapillaries in the originally filed specification is respectfully suggested. See MPEP § 2163 particularly § 2163.06.
Claims 1, 7, 11, 49 and 50 will remain rejected until Applicant cancels all new matter.
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 7, 11, 49 and 50 are rejected under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Rossi et. al. (hereinafter “Rossi”) (US Patent Application Publication 20190119642, published April 25, 2019) as evidenced by Sackstein (US Patent Application Publication No. 20240272156, published August 15, 2024); and Ghirardello et al. (hereinafter “Ghirardello”) (Nature Communications, 2025, 16(11279), 1-28). This is a new rejection necessitated by amendment of the claims in the response filed 07-27-2026.
Regarding claims 1, 11, 49 and 50, Rossi teaches that Figure 46A-B demonstrates the absolute number of Lin-CD45RA-CD90+CD49f+EPCR+ HSCs after 12 days of culture, where Figure 46A depicts that absolute number of immunophenotypic HSCs (Lin-CD34+CD45RA-CD90+CD49f+ EPCR+) arising from 10,000 CD34+ enriched cord blood cells in each well after twelve days of culture in the indicated conditions; while Figure 46B depicts a table of statistically significant p values for DMSO versus expanded cells shown in in Figure 46A (interpreting cord blood as a heterogenous population of HSPCs; and interpreting cells consisting essentially of the markers CD34+/CD38-/CD90+/CD45RA-/CD49f+; and consisting of sLeX levels exceeding 85%, 90%, 95% and 99%, claims 1, 11, 49 and 50) (paragraph [0444]; and Figure 4), wherein it is known that the HSPC subset defined by markers CD34+/CD38-/CD90+/CD45RA-/CD49f+ (conventional HSCs) (HSC-conv) displays the highest sLeX levels and most potent E-selectin binding of any human cell as evidenced by Sackstein (paragraph [0106], lines 16-19). Rossi teaches that Figure 10 shows a series of FACS diagrams obtained from the analysis of hematopoietic stem cells obtained from human mobilized peripheral blood and cultured in the presence of the indicated reagents for 14 days, wherein the reagent names are as indicated in Figures 2-5 (interpreted as a heterogenous population of CE34+ HSPCs; and contacting with binding molecules, claim 1) (paragraph [0408]; and Figures 2-5 and 10). Rossie teaches that CD34+ enriched cord blood cells were obtained from All Cells, wherein ten thousand cells were cultured in StemSpan SFEMII containing recombinant human SCF, TPO, IL-3 and FLT3L (all at 100 ng/ml), such that cells were cultured with cytokine containing media with the vehicle control (DMSO) or the indicated small molecules (interpreted as contacting with a binding molecule, claim 1) (paragraph [0418]; and Figure 20). Rossi teaches in Figure 21, representative Dot Plots and gating strategy for expanded CD34+ cord blood cells, such that on day 12 after culture in the indicated compounds, samples were analyzed by flow cytometry, wherein plots show samples previously gated through live (PI-) and singlet gates; and the gating strategy for immunophenotypic hematopoietic stem cells (HSCs) defined as Lin-CD34+CD45RA-CD90+ and Lin-CD34+CD45RA-CD90+CD49f+ EPCR+ HSCs is shown (interpreted as collecting a subpopulation of cells that natively express sLeX at a level that exceeds 85% of the sLeX expression level of cells before expansion, claim 1) (paragraph [0419]; and Figure 21). Rossi teaches that Figure 47 depicts the frequency of Lineage-CD34+ HECA+ cord blood cells, wherein frequency of human Lineage CD34+ cells that are HECA+ on day 12 after culture in the indicated compounds, such that no statistically significant differences were detected using one-way ANOVA and Tukey's multiple comparisons tests (interpreting cord blood as comprising a heterogenous population of human HSPCs; and CD34+ HSPCs, claim 1) (paragraph [0445]; and Figure 47). Rossi teaches that Figure 48A-B depict HECA MFI staining on immunophenotypic Lin-CD34+ HSPCs, such that using the antibody clone HECA-452, which recognizes sialo-fucosylated glycans and sialyl Lewis x (sLex) on the cutaneous lymphocyte antigen (CLA), wherein CLA binds E-selectin and has been shown to increase homing of cord blood progenitors to the bone marrow following transplantation, such that Figure 48A depicts the mean fluorescence intensity of HECA on the surface of Lin-34+ cells; and Figure 48B is a table of statistically significant p values for DMSO cultured cells compared to compound expanded cells (interpreting HECA, HECA-452, and E-selectin as binding molecules; and interpreting detecting fluorescence intensity as measuring sLex natively expressed, claim 1) (paragraph [0446]; and Figure 48), wherein it is known that fucosylation is a ubiquitous glycosylation event that shapes cellular communication and immunity; and glycosylation is one of the most structurally diverse post-translational modifications in nature as evidenced by Ghirardello (Abstract, lines 1-2; and pg. 1, col 1, first partial paragraph).
Regarding claim 7, Rossi teaches that CD34+ cord blood cells were cultured in vitro in the presence of different combinations of compounds as described herein, wherein the percentage and total number of Lin-CD34+ and Lin- cells was increased (Figure. 21; Figure 22A-22B; Figure. 23A-23B) in the presence of POM, (pomalidomide); SRl (StemRegenin 1); A (A83-01), U (UM171); AP (A+POM);APU (A+POM+UM171) and APSRl (A+POM+SRI), such that all conditions tested increase CD34+ cell number, which includes both HSCs and progenitor cells (interpreted as contacting CD34+ HSPCs from cord blood with a binding molecule, claims 1 and 7) (paragraph [0965]; and Figures 21, 22 and 23).
Rossi meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Claim Rejections - 35 USC § 103
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 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 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.
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.
Claims 1, 7, 11, 49 and 50 are rejected under 35 U.S.C. 103 as being unpatentable over Rossi et. al. (hereinafter “Rossi”) (US Patent Application Publication 20190119642, published April 25, 2019) in view of He et. al. (hereinafter “He”) (Journal of Stem Cell Research & Therapy, 2016, 6(8), 1-7) as evidenced by Sackstein (US Patent Application Publication No. 20240272156, published August 15, 2024); and Ghirardello et al. (hereinafter “Ghirardello”) (Nature Communications, 2025, 16(11279), 1-28).
This is a new rejection necessitated by amendment of the claims in the response filed 07-27-2026.
The teachings of Rossi as applied to claims 1, 7, 11, 49 and 50 are described supra.
Rossi does not specifically exemplify additional methods of collecting a subpopulation of cells natively expressing sLeX (11, 49 and 50, all in part).
Regarding claims 11, 49 and 50 (all in part), He teaches that glycosylation of proteins and lipids on cell surfaces have been shown to be important in maintaining pluripotency and stem cell fate in embryonic stem cells; and that lectins have been widely used to characterize carbohydrate modifications on cell surface of embryonic stem cells to determine pluripotency and stem cell fate, such that a panel of 14 lectins and carbohydrate antibodies was used to characterize the carbohydrate surface markers of mouse Embryonic Stem (ES) Cells, wherein SSEA-1-positive mouse ES cells were firstly enriched and the carbohydrate profile of the cells was determined by flow cytometry and immunocytochemistry, such that enrichment of mouse ES cells yielded approximately 99.95 ± 0.87% of SSEA-1-positive mouse ES cells (interpreted as exceeding 90% of the sLeX expression level, claims 11, 49 and 50) (Abstract, lines 1-7). He teaches that cell surface carbohydrate expression of SSEA-1 enriched mouse ES cells was assessed by indirect immunofluorescence detected by flow cytometry to provide a quantitative binding percentage and fluorescence intensity of SSEA-1 Ab, carbohydrate antibodies and lectins, wherein FACSCalibur equipped with an argon laser with emission wavelength at 488 nm was used; wherein flow cytometry results presented here are from mESCs that were used immediately after the SSEA-1 positive cell enrichment procedure; and CellQuest Pro software was used for cell acquisition and analysis, such that mouse ES cells were prepared, cultured and harvested into single cell suspensions using trypsinization as described above (interpreted as enrichment, claim 1) (pg. 2, col 2, first full paragraph, lines 1-12). He teaches that murine ES cells were grown in 10 cm dishes and trypsin/EDTA passaged into single cell suspensions as described above, cells were incubated at 4°C for 30 minutes in 1:10 dilution of purified anti-mouse IgM in D/G buffer; a 1:4 dilution of secondary anti-mouse IgM-beads in D/G buffer were added to the cell pellet, and the re-suspended pellet was incubated at 4°C for 5 minutes; centrifuged; repeated; subjected to a magnetic bead column; the cells were counted; and subjected to flow cytometry to enrich SSEA-1 positive mouse embryonic stem cells (ESCs) (interpreted as a enriching HSC) (pg. 2, col 1, last partial paragraph; and col 2, first partial paragraph). He teaches that cells were double stained with one of the 14 carbohydrate antibodies and lectins and SSEA-1 Ab, then stained with secondary antibodies after washing with PBS, wherein the secondary antibodies were chosen so that there would not be any overlap in the emission/ excitation wavelengths and so that double staining could be performed (interpreted as contacting HSPCs with a binding molecule, claim 1) (pg. 2, col 2, first full paragraph, lines 20-24). He teaches that Figure 4 shows carbohydrate expression determined by lectins and carbohydrate antibodies using the immunocytochemistry method including SSEA-1 (pg. 5, col 1, Figure 4). Figure 4 is shown below:
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He teaches a sorting method to enrich SSEA-1 positive mouse ES cells, such that after enrichment, about 99.95 ± 0.87% of mouse ES cells were SSEA-1 positive (Figure 1), such that to determine the presence and binding percentage of 14 chosen carbohydrate Abs and lectins on pluripotent mouse ES cell surfaces, both karyotypically normal mouse ES cell lines (ES-D3 and ESC57BL/6) were analyzed using flow cytometry with the panel of Abs and lectins together with the pluripotency marker, SSEA-1, wherein a broad range of binding percentages was observed (Figure 2), such that the highest binding percentages were detected using PNA, DSL, JAC, GNL, PSA, AAL and LTL; and the binding percentages for PNA, DSL, JAC and GNL were similar to that of SSEA-1, which showed over 99.9% of positive binding in enriched mouse ES cells (interpreted as exceeding 85%, 90%, 95% and 99% sLeX expression level, claims 1, 11, 49 and 50) (pg. 3, col 2, first partial paragraph; and Figures 1 & 2).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of enriching cells in SSEA-1 as exemplified by He, it would have been prima facie obvious for one of ordinary skill in the art at the time the invention was made to modify the method of expanding, enriching, and/or maintaining a population of HSPCs ex vivo including using binding molecules such as the antibody HECA-452, CLA, E-selectin, etc. as disclosed by Rossi to include methods of analyzing cell surface carbohydrate expression including by flow cytometry, immunocytochemistry, and/or immunofluorescence as taught by He with a reasonable expectation of success in detecting, selecting and/or enriching cells that express specific cell surface carbohydrates including lin-CD34+ cells expressing sLeX; to increase the homing of cord blood progenitors including lin-CD34+ cells expressing sLeX to the bone marrow following transplantation; and/or in examining the patterns of cell surface carbohydrate expression including cells expressing sLex expression within a heterogenous population of HSPCs.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly
rejected under 35 USC §103(a) as obvious over the art.
Conclusion
Claims 1, 7, 11, 49 and 50 remain rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/
Primary Examiner, Art Unit 1684
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