DETAILED ACTION
Applicant’s amendment and Arguments/Remarks received on 04 June 2026 have been entered. Claims 1 and 5-23 were previously pending in the application. Claims 10 and 17-23 have been cancelled, and new claims 24-30 have been added by Applicant. Claims 1, 5-9, 11-16, and 24-30 are currently pending in the application. Claims 1, 5, 7, 8, 9, 11, 12, 13, 14, and 16 are independent claims.
The election of Group I, drawn to a use of markers for isolation or enrichment of HSCs or a cell population containing HSCs, isolated or enriched HSCs or a cell population containing HSCs, a second isolated or enriched HSCs or a cell population containing HSCs, and a composition or kit for identifying, detecting, isolating, or enriching HSCs, remains in effect in the instant application.
Claims 8-9 and 11-14 remain withdrawn from consideration as being directed to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 5-7, 15-16, and 24-30 are currently pending and under examination in the instant application. An action on the merits follows.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/JP2021/025050, filed 01 July 2021, which claims priority to JAPAN PCT/JP2020/025915, filed 01 July 2020, and JAPAN 2021-089502, filed 27 May 2021. Filing of certified English translations for the foreign priority applications JAPAN PCT/JP2020/025915, filed 04 June 2026, and JAPAN 2021-089502, filed 04 June 2026, are acknowledged.
Thus, the earliest possible priority for the instant application is 01 July 2020.
Specification
The objection to the specification of the disclosure for reciting trade name(s) or mark(s) used in commerce without the corresponding symbols and/or generic terminology is withdrawn in view of the amendment to the specification. The amendment to the specification of the disclosure filed 04 June 2026 has been entered.
Claim Objections
The objection to amended claims 5 and 6 for reciting “one or more selected from”, without a noun being modified by the “one or more” is withdrawn in view of the amendment to claims.
**The following new objection is necessitated by amendments to the claims.
Amended independent claim 1 is objected to because of the following informalities: claim 1 recites, “to prepare and isolated or enriched cell population” in lines 12-13, which appears to be a typographical error wherein “and” recited in line 12 should be “an”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The rejection of amended, previously presented, and cancelled claims 1, 5-7, 15-16, and 18 under 35 U.S.C. 112(b) as failing to particularly point out and distinctly claim the subject matter which the inventor(s) regards as the invention for multiple issues of indefiniteness is withdrawn over amended and cancelled claims 1, 18, maintained over amended claims 5-7 and 15-16, and newly applied to new claims 26, 28, and 30. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended independent claim 5 to recite “one or more markers selected from (1) …, or (2) markers selected from (a) …, (b) …, and (c) …, or (3) a combination of (1) and (2)”, which has multiple issues of indefiniteness outstanding.
Firstly, amended claim 5 is still indefinite in that “one or more markers selected from” is not clear as to whether the recited list is meant to be a closed or open list.
Secondly, “one or more markers selected from” in lines 4-5 modifying (1) a list of 38 required markers, (2) options of 2 or 3 required markers, or (3) a combination of the 38 required markers with the 2 or 3 required markers. Therefore, it is unclear how there can be an option of “one or more markers” in that none of the recited options present an option for only a single marker to be used.
As such, the metes and bounds of the claim still cannot be determined.
Claims 6-7, 15-16, 26, 28, and 30 are included in the rejection due to their dependent on or encompassing of independent claim 5.
**The following new rejection is necessitated by Applicant’s amendments to the claims.
Amended claims 1, 24-25, 27, and 29 are newly 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. Claims 25, 27, and 29 are included in this rejection due to its encompassing of amended independent claim 1 and/or new claim 24.
Amended independent claim 1 has multiple new issues of indefiniteness.
Amended independent claim 1 now recites, “an expression pattern selected from the group consisting of (1) one or more markers selected from the group consisting of …, (2) markers selected from the group consisting of (a) a combination of CD48 and CD34, (b) a combination of CD48 and c-Kit, and (c) a combination of CD48, CD34, and c-Kit, or (3) a combination of (1) and (2)”, which is indefinite because it is unclear how the method can comprise an index expression pattern of markers consisting of a combination of both (1) and (2) wherein each of (1) and (2) recite groups consisting of their respective markers which are overlapping, but not identical. For example, (1) recites numerous markers not recited in (2) and (2) recites CD34, which is not recited in (1). Therefore, there are no options of marker sets which conform to the closed sets of markers recited in both (1) and (2).
Additionally, amended independent claim 1 now recites “an expression pattern selected from the group consisting of (1) …, or (2) …, (3) …”, which is indefinite because it is unclear which options of (1), (2), or (3) are included in the group of expression patterns.
As such, the metes and bounds of the claim cannot be determined.
New claim 24 recites “wherein an expression pattern of markers selected from (1)…, (2)…, and (3)… is used as said index”, which is indefinite because it is unclear whether Applicant intends to encompass both options (2) and (3) of independent claim 1, which each comprise the recited markers, or whether Applicant intends to limit claim 24 to only option (2) of independent claim 1, which specifically recites the markers recited in new claim 24. As such, it is unclear whether Applicant intends to limit the invention to only CD48(-), CD34(+), and c-Kit(+) or whether Applicant intends to also encompass markers recited in independent claim 1 option (1).
Additionally, by reciting “markers selected from”, new claim 24 conflicts with amended independent claim 1, which recites “markers selected from the group consisting of” in line 9. As such, it is unclear whether Applicant intends new claim 24 to be broader than amended independent claim 1.
As such, the metes and bounds of the claim cannot be determined.
Claim Interpretation
Note that amended independent claims 1 and 5 recite steps of isolating or enriching HSCs or a cell population comprising HSCs, but do not require the HSCs to be in any particular state or from any particular source. As such, claims 1 and 5 encompass HSCs from any species which have HSCs. Claims 1 and 5 also encompass HSCs which have undergone any prior manipulations, including any prior separation, selection, isolation, enrichment, purification, or culturing steps.
Amended independent claim 5 now recites an option of (1) which lists 38 markers joined by the linker word “and”, and so has been interpreted to require using all 38 of the of markers recited in lines 5-8 when option (1) is selected. Note that although the instant disclosure does not explicitly teach to utilize all 38 markers, the specification provides support by implicitly teaching to use all the markers as encompassed by the teaching to selected one, two, three, four, five, “or more” of the markers [such as in 0010-0021, 0026, 0028].
Claim Rejections - 35 USC § 101
The rejection of amended claim 1 under 35 U.S.C. 101 as being directed to non-statutory subject matter is withdrawn in view of Applicant’s amendments to claim 1 to recite a method of isolating or enriching hematopoietic stem cells or a cell population containing hematopoietic stem cells.
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 (i.e., changing from AIA to pre-AIA ) 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 rejection of amended, previously presented, and cancelled claims 1, 5-7, 15-16, and 18 under 35 U.S.C. 102(a)(1) as being anticipated by Tornack et al. [2017, European Journal of Immunology, 47, 1477-1487], is withdrawn over amended and cancelled claims 1 and 18 and maintained over amended and previously presented claims 5-7 and 15-16 in view of Applicant’s amendment closing the groups of markers in claim 1 to only those recited within the claim. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended the claims to address issues of indefiniteness which did not alter the scope of the claims sufficiently to overcome a finding of anticipation by Tornack.
Applicant argues that:
the group of markers recited in claim 5 only partially overlap with the cited groups of markers which is not sufficient for anticipation;
the claimed combinations of 1) CD48(-) and CD34(+), 2) CD48(-) and c-kit(+), and 3) CD48(-), CD34(+), and c-kit(+) are particularly effective for isolating or enriching hematopoietic stem cells, and especially those of primates, such that the claimed combinations have an unexpected result of being surprisingly useful for isolating or enriching hematopoietic stem cells of primates;
the finding in mice is not applicable to primates in the field of stem cells; and
the role of a single marker reported as a member of a combination marker like the one reported in Tornack was difficult to understand and the effect of a new combination of such a marker with a different marker is unpredictable.
However, this is not agreed.
Regarding Applicant’s argument 1), note that for a reference to anticipate a claim which recites alternative options, the reference must teach only one of the recited options and is not required to teach all alternatively recited options. See MPEP 2131.02(II), which states that “A genus does not always anticipate a claim to a species within the genus. However, when the species is clearly named, the species claim is anticipated no matter how many other species are additionally named. See Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990) (The claimed compound was named in a reference which also disclosed 45 other compounds. The Board held that the comprehensiveness of the listing did not negate the fact that the compound claimed was specifically taught. The Board compared the facts to the situation in which the compound was found in the Merck Index, saying that "the tenth edition of the Merck Index lists ten thousand compounds. In our view, each and every one of those compounds is ‘described’ as that term is used in [pre-AIA ] 35 U.S.C. 102(a), in that publication."). Id. at 1718. See also In re Sivaramakrishnan, 673 F.2d 1383, 213 USPQ 441 (CCPA 1982) (The claims were directed to polycarbonate containing cadmium laurate as an additive. The court upheld the Board’s finding that a reference specifically naming cadmium laurate as an additive amongst a list of many suitable salts in polycarbonate resin anticipated the claims. The applicant had argued that cadmium laurate was only disclosed as representative of the salts and was expected to have the same properties as the other salts listed while, as shown in the application, cadmium laurate had unexpected properties. The court held that it did not matter that the salt was not disclosed as being preferred, the reference still anticipated the claims and because the claim was anticipated, the unexpected properties were immaterial.).”
Independent claim 5 recites a list of options for expression patterns to be used in isolating or enriching HSCs. Tornack clearly teaches at least one of the options recited by the claims by teaching isolation including the combination of CD48(-) and c-Kit(+) expression [abstract]. Therefore, Tornack anticipates the claimed invention as recited in amended and previously presented claims 5-7 and 15-16.
Regarding Applicant’s argument 2), note that unexpected results or surprising utility is not a basis for overcoming an anticipation rejection under 35 U.S.C. 102(a)(1). As discussed above and recited in MPEP 2131.02(II) with respect to a claim of unexpected properties in response to an anticipation rejection under 35 U.S.C. 102(a)(1), “the court held that … the reference still anticipated the claims and because the claim was anticipated, the unexpected properties were immaterial.”
Regarding Applicant’s argument 3), note that the instant claims do not limit the claimed invention to any particular species other than inherently limiting to those comprising hematopoietic stem cells.
Regarding Applicant’s argument 4), note that instant claim 5, and those dependent thereon, does not preclude the use of markers in addition to those recited in the claims. As such, as discussed above and in the prior action, Tornack teaches a specific combination of markers which includes those recited in the claims, thereby anticipating the instant invention as claimed. Because Tornack anticipates the instantly claimed invention, there is no need to predict the role of a single marker nor to understand the effect of a new combination of such a marker with a different marker.
Therefore, Applicant’s arguments do not overcome a finding of anticipation by Tornack under 35 U.S.C. 102(a)(1), and the rejection is maintained.
**The following new rejection is necessitated by Applicant’s amendments to the claims.
Amended and new claims 1 and 24 are newly rejected under 35 U.S.C. 102(a)(1) as being anticipated by McKinney-Freeman [2009, Blood, 114(2), 268-278].
Note that the claim as written does not include any limitations as to the source or condition of the hematopoietic stem cells (HSCs) or the cell population containing hematopoietic stem cells which are subjected to the step of isolating. As such, amended independent claim 1 encompasses any method which comprises any steps of isolating or enriching HSCs which use an expression pattern index of markers selected from the group consisting of (1), (2), or (3) as recited in the claim. Additionally, independent claims 1 and 24 encompass isolating or enriching HSCs from any species.
McKinney-Freeman teaches a method of isolating or enriching murine hematopoietic stem cells using, as an index, an expression pattern consisting of c-kit(+), CD34(+), and CD48(-) to prepare isolated or enriched HSCs from E12.5 fetal liver or placenta[Figure 2B]. McKinney-Freeman additionally teaches that the HSCs isolated or enriched thereby are capable of long-term repopulation [Table 2, Figure 2C-F].
Accordingly, by teaching all of the limitations of claims 1 and 24 as written, McKinney-Freeman anticipates the instant invention as claimed.
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:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. 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.
**The following new rejection is necessitated by amendments to the claims.
Amended and new claims 1 and 24-25, 27, and 29 are newly rejected under 35 U.S.C. 103 as being unpatentable over McKinney-Freeman [2009, Blood, 114(2), 268-278]; in view of Briddell et al. [1992, Blood, 79(12), 3159-3167] and Jobin et al. [2015, Cytotherapy, 17, 1472-1484].
Note that the claim as written does not include any limitations as to the source or condition of the hematopoietic stem cells (HSCs) or the cell population containing hematopoietic stem cells which are subjected to the step of isolating. As such, amended independent claim 1 encompasses any method which comprises any steps of isolating or enriching HSCs which use an expression pattern index of markers selected from the group consisting of (1), (2), or (3) as recited in the claim. Additionally, independent claims 1 and 24 encompass isolating or enriching HSCs from any species.
Regarding claims 1 and 24, McKinney-Freeman teaches a method of isolating or enriching murine hematopoietic stem cells using, as an index, an expression pattern consisting of c-kit(+), CD34(+), and CD48(-) to prepare isolated or enriched HSCs from E12.5 fetal liver or placenta [Figure 2B]. McKinney-Freeman additionally teaches that the HSCs isolated or enriched thereby are capable of long-term repopulation [Table 2, Figure 2C-F].
Regarding claims 25, 27, and 29, McKinney-Freeman does not teach wherein the HSCs are from primates nor that they are human HSCs.
However, Briddell teaches a method comprising using c-kit expression to isolate human HSCs, wherein the isolated human HSCs are CD34(+), c-kit(+), and HLA-DR(-) [pg 3159 col 2 ¶ 2, Table 3, Figure 1]. Briddell also teaches that the breadth of response of Kit ligand on progenitor cells of various lineages in addition to its action on the HPP-CFC and LTBMC-IC suggest that the true human HSC might express the KR/c-kit [pg 3163 col 2 ¶ 1]. Briddell also teaches that they and others have proposed to use KR/c-kit antibodies to further isolate human hematopoietic progenitor cells [pg 3163 col 2 ¶ 2]. Therefore, given the teachings of Briddell to use c-kit antibodies to isolate human hematopoietic progenitor cells/ HSCs, the ordinarily skilled artisan would have been motivated to use c-kit expression for the isolation of human HSCs.
Additionally, Jobin teaches that human HSCs do not express CD48 and do express CD34, wherein CD48 expression is gained in subsequent differentiation into downstream progenitor cells and CD34 expression is lost in downstream progenitor cells [Table I, Figure 5]. Therefore, the ordinarily skilled artisan at the time of filing the instant application would have been motivated to use CD48(-) and CD34(+) expression in the isolation of HSC to discriminate them from downstream progenitor cells.
Given the motivation taught by Briddell to use c-kit expression for the isolation of human HSCs; and the motivation taught by Jobin to use CD48(-) and CD34(+) expression in the isolation of HSC to discriminate them from downstream progenitor cells; it would have been prima facie obvious to an ordinarily skilled artisan at the time of filing the instant application to modify the method of McKinney-Freeman to use the expression profiles of markers CD34(+), c-kit(+), and CD48(-) taught by McKinney-Freeman for the isolation of human HSCs with a reasonable expectation of success.
Insofar as Applicant’s arguments apply to this new grounds of rejection, Applicant argues that:
the group of markers recited in claims 1 and 5 only partially overlap with the cited groups of markers which is not sufficient for anticipation;
the claimed combinations of 1) CD48(-) and CD34(+), 2) CD48(-) and c-kit(+), and 3) CD48(-), CD34(+), and c-kit(+) are particularly effective for isolating or enriching hematopoietic stem cells, and especially those of primates, such that the claimed combinations have an unexpected result of being surprisingly useful for isolating or enriching hematopoietic stem cells of primates;
the finding in mice is not applicable to primates in the field of stem cells; and
the role of a single marker reported as a member of a combination marker like the one reported in Tornack was difficult to understand and the effect of a new combination of such a marker with a different marker is unpredictable.
However, this is not agreed.
Regarding Applicant’s argument 1, note that McKinney-Freeman teaches a method of isolating HSCs which consists of using CD34(+), c-kit(+), and CD48(-) as an index for isolating or enriching HSCs. As such, McKinney-Freeman teaches the specific combination of markers recited in instant claims 1 and 24.
Regarding Applicant’s argument 2, McKinney-Freeman teaches a method of isolating HSCs which consists of using CD34(+), c-kit(+), and CD48(-) as an index for isolating or enriching HSCs. Additionally, Briddell and Jobin provide the teachings and motivation for an ordinarily skilled artisan to modify the method of McKinney-Freeman for the isolation of human HSCs. Additionally, Applicant has not provided any data to support the assertion of unexpected and surprising results. As such, Applicant’s argument amounts to arguments of counsel. The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness."). See MPEP § 716.01(c) for examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration. Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the applicant. MPEP 716.01(c). Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
It is also noted that any evidence of unexpected results must be commensurate in scope with the claimed invention, and that a greater, or greater than additive, effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected MPEP 716.02 (a) and (d). Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). Note that independent claim 1 does not limit the invention to specifically primate nor specifically human HSCs. Additionally, independent claim 1 does not limit the invention to an index consisting of specifically CD34(+), c-kit(+), and CD48(-). Therefore, Applicant’s asserted unexpected results are not commensurate in scope with the instantly claimed invention.
Regarding Applicant’s argument 3, note that Briddell and Jobin provide the teachings and motivation for an ordinarily skilled artisan to modify the method of McKinney-Freeman for the isolation of human HSCs by teaching wherein human HSCs are also CD34(+), CD48(-), and c-kit(+) and to use such markers for the isolation and identification of HSCs. Therefore, the cited art provide specific teachings for the use of these markers in humans and the rejection does not rely upon merely applying teachings from mouse for the isolation of human cells.
Regarding Applicant’s argument 4, note that McKinney-Freeman teaches specifically to isolate HSCs using an index consisting of gene expression patterns of CD34(+), CD48(-), and c-kit(+). Therefore, this is no effect of single markers or new combinations of markers to consider.
Therefore, Applicant’s arguments do not overcome a finding of obviousness for claims 1, 24-25, 27, and 29 under 35 U.S.C. 103 over McKinney-Freeman, Briddell, and Jobin.
**The following new rejection is necessitated by amendments to the claims.
Amended and new claims 5-7, 15-16, 26, 28, and 30 are newly rejected under 35 U.S.C. 103 as being unpatentable over Tornack et al. [2017, European Journal of Immunology, 47, 1477-1487]; in view of Briddell et al. [1992, Blood, 79(12), 3159-3167] and Jobin et al. [2015, Cytotherapy, 17, 1472-1484].
Regarding amended independent claim 5, Tornack teaches a method for isolating or enriching HSCs comprising a) preparing a cell population containing HSCs; and b) isolating or enriching cells depending on an expression pattern of one or more markers selected from at least CD11c, CD41, CD31, CD48, CD34, and/or c-Kit [abstract, column 3 ¶ 3, column 4 ¶ 2, column 15 ¶ 2, 5, column 16 ¶ 2, Figure 1, 2, 3, 4].
Regarding claim 6, Tornack teaches wherein an expression pattern used as an index to select a cell population for isolation or enrichment includes an expression pattern combination of CD48(-) and c-kit(+) [abstract, column 3 ¶ 3, column 4 ¶ 2, column 15 ¶ 2, Figure 1].
Regarding claim 7, Tornack teaches a sorted isolated population of HSCs produced by the method of using one or more markers selected from at least CD11c, CD41, CD31, CD48, CD34, and/or c-Kit to isolate HSCs [abstract, column 3 ¶ 3, column 4 ¶ 2, column 15 ¶ 2, Figure 1, 2, 3, 4].
Regarding claim 15, Tornack teaches wherein the cell population containing HSCs is obtained from a living body (e.g., 8-10 weeks old male mice) [column 15 ¶ 5-column 16 ¶ 2].
Regarding claim 16, Tornack teaches an isolated HSC population produced by the method of using one or more markers selected from at least CD11c, CD41, CD31, CD48, CD34, and/or c-Kit to isolate HSCs, wherein the cell population containing HSCs is obtained from a living body (e.g., 8-10 weeks old male mice) [column 15 ¶ 5-column 16 ¶ 2].
Regarding new claims 26, 28, and 30, Tornack does not teach wherein the HSCs are from primates nor wherein they are human HSCs.
However, Briddell teaches a method comprising using c-kit expression to isolate human HSCs, wherein the isolated human HSCs are CD34(+), c-kit(+), and HLA-DR(-) [pg 3159 col 2 ¶ 2, Table 3, Figure 1]. Briddell also teaches that the breadth of response of Kit ligand on progenitor cells of various lineages in addition to its action on the HPP-CFC and LTBMC-IC suggest that the true human HSC might express the KR/c-kit [pg 3163 col 2 ¶ 1]. Briddell also teaches that they and others have proposed to use KR/c-kit antibodies to further isolate human hematopoietic progenitor cells [pg 3163 col 2 ¶ 2]. Therefore, given the teachings of Briddell to use c-kit antibodies to isolate human hematopoietic progenitor cells/ HSCs, the ordinarily skilled artisan would have been motivated to use c-kit expression for the isolation of human HSCs.
Additionally, Jobin teaches that human HSCs do not express CD48 and do express CD34, wherein CD48 expression is gained in subsequent differentiation into downstream progenitor cells and CD34 expression is lost in downstream progenitor cells [Table I, Figure 5]. Therefore, the ordinarily skilled artisan at the time of filing the instant application would have been motivated to use CD48(-) and CD34(+) expression in the isolation of HSC to discriminate them from downstream progenitor cells.
Given the motivation taught by Briddell to use c-kit expression for the isolation of human HSCs; and the motivation taught by Jobin to use CD48(-) and CD34(+) expression in the isolation of HSC to discriminate them from downstream progenitor cells; it would have been prima facie obvious to an ordinarily skilled artisan at the time of filing the instant application to modify the method of Tornack to use the expression profiles of markers comprising c-kit(+) and CD48(-) as taught by Tornack, along with CD34(+), for the isolation of human HSCs with a reasonable expectation of success.
Insofar as applicant’s arguments apply to this new grounds of rejection, Applicant argues that:
the group of markers recited in claims 1 and 5 only partially overlap with the cited groups of markers which is not sufficient for anticipation;
the claimed combinations of 1) CD48(-) and CD34(+), 2) CD48(-) and c-kit(+), and 3) CD48(-), CD34(+), and c-kit(+) are particularly effective for isolating or enriching hematopoietic stem cells, and especially those of primates, such that the claimed combinations have an unexpected result of being surprisingly useful for isolating or enriching hematopoietic stem cells of primates;
the finding in mice is not applicable to primates in the field of stem cells; and
the role of a single marker reported as a member of a combination marker like the one reported in Tornack was difficult to understand and the effect of a new combination of such a marker with a different marker is unpredictable.
However, this is not agreed.
Regarding Applicant’s argument 1, note that Tornack teaches a method of isolating HSCs which comprises using c-kit(+) and CD48(-) as an index for isolating or enriching HSCs. As such, Tornack teaches the specific combination of markers recited in instant claims 5 and 6.
Regarding Applicant’s argument 2, Tornack teaches a method of isolating HSCs which comprises using c-kit(+) and CD48(-) as an index for isolating or enriching HSCs. Additionally, Briddell and Jobin provide the teachings and motivation for an ordinarily skilled artisan to modify the method of Tornack for the isolation of human HSCs. Additionally, Applicant has not provided any data to support the assertion of unexpected and surprising results. As such, Applicant’s argument amounts to arguments of counsel. The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness."). See MPEP § 716.01(c) for examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration. Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the applicant. MPEP 716.01(c). Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
It is also noted that any evidence of unexpected results must be commensurate in scope with the claimed invention, and that a greater, or greater than additive, effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected MPEP 716.02 (a) and (d). Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). Note that independent claim 5 does not limit the invention to specifically primate nor specifically human HSCs. Additionally, independent claim 5 does not limit the invention to an index consisting of specifically CD34(+), c-kit(+), and CD48(-). Therefore, Applicant’s asserted unexpected results are not commensurate in scope with the instantly claimed invention.
Regarding Applicant’s argument 3, note that Briddell and Jobin provide the teachings and motivation for an ordinarily skilled artisan to modify the method of Tornack for the isolation of human HSCs by teaching wherein human HSCs are also CD34(+), CD48(-), and c-kit(+) and to use such markers for the isolation and identification of HSCs. Therefore, the cited art provide specific teachings for the use of these markers in humans and the rejection does not rely upon merely applying teachings from mouse for the isolation of human cells.
Regarding Applicant’s argument 4, note that Tornack teaches specifically to isolate HSCs using an index consisting of gene expression patterns of CD48(-) and c-kit(+). Therefore, there is no effect of single markers or new combinations of markers to consider with respect to modifying the prior art to arrive at the instantly claimed invention.
Therefore, Applicant’s arguments do not overcome a finding of obviousness for claims 5-7, 15-16, 26, 28, and 30 under 35 U.S.C. 103 over Tornack, Briddell, and Jobin.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
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, Maria G. Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
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