0DETAILED 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 .
Election/Restrictions
Applicant’s election without traverse of Group 1, claims 1-5 in the reply filed on March 9, 2026 is acknowledged.
Claims 4-17 have been canceled. Claims 18-26 have been newly added.
Newly submitted claims 24-26 are directed to an invention that lacks unity with the invention originally claimed for the following reasons: Newly added claims 24-26 are drawn to an endothelial progenitor cell (EPC) having enhanced vasculogenesis wherein the cell is prepared by the method of culturing EPCs with PDGF-BB. The technical feature of culturing of EPCs with PDGF-BB is known in the art based on the teachings of Liang et al. and therefore is not a special technical feature. Liang et al. teach culture of EPCs with PDGF-BB (Pg. 1724, right col., 1st para. and Fig. 2A) and that PDGFR (used as a market for increased PDGF signaling) and Notch1 are enhanced by culture with PDGF-BB and that PDGF and Notch signaling are involved in vasculogenesis (Abstract).
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 Accordingly, claims 24-26 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 1-3 and 18-23 are examined on the merits.
Priority
The instant application is a 35 U.S.C 371 national stage filing of the International Application No. PCT/KR2022/002713 filed on February 24, 2022. The instant application claims foreign priority under 35 U.S.C 119(a)-(d) to Korean Patent Application KR10-2021-0026420, filed on February 26, 2021. Receipt is acknowledged of a certified copy of the foreign patent application in the original language as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on August 25, 2023 and October 24, 2025 are in compliance with the provisions of 37 CFR 1.97 and are being considered by the examiner.
Drawings
Figure 1B of the Specification references FITC-UEA-I binding as indicated by green coloring and vWF as indicated by red coloring (Pgs. 7 and 22) however, all images supplied are in black and white.
Figures 9 and 10 of the Specification also reference merged images of fluorescent staining while the images supplied are in black and white (Pgs. 8, 27-28).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Objections to the Specification
The disclosure is objected to because of the following informalities: The FIG. 1 captions for FIG. 1D recited in the amended specification dated August 25, 2025 indicate that FIG 1D shows analysis of cell surface markers in passages 1 to 3. Amended FIG. 1D dated November 7, 2023 depicts cell surface markers in passaged 1 to 4.
Appropriate correction is required.
The amendment filed November 7, 2023 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: Applicant’s amended drawings of Fig. 1D dated November 7, 2023 shows characterization of cell surface markers in passages 1-4 which was not disclosed in the original specification. Additionally, FIG. 1D dated August 25, 2023 and FIG. 1D dated November 7, 2023 appear to depict different data.
Applicant is required to cancel the new matter in the reply to this Office Action.
Claim Objections
Claim 23 is objected to because of the following informalities: instant claim comprises a typographical error and should state “the” endothelial progenitor cells.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 3 and 19-23 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 3, which depends from claim 1, recites the limitation "the endothelial progenitor cells treated…" in line 2. There is insufficient antecedent basis for this limitation in the claim as the prior recitation is to treating and culturing EPCs with PDGF-BB. As claimed, it is unclear whether the instantly recited “treated” is intended to refer to treating and culturing of EPCs or a different treatment. Appropriate correction is required.
Claim 19, which depends from claim 1, recites the limitation "the endothelial progenitor cells" in line 1. Claim 1 has two recitations of endothelial cells: the prepared endothelial cells having increased vasculogenesis and the isolated endothelial progenitor cells which are treated and cultured with PDGF-BB. As claimed, it is not clear which population of endothelial progenitor cells are to be characterized by being negative for CD31, CD309, CD45, and CD34. Appropriate correction is required.
Claims 20-22, which depend from claim 1, recites the limitations "the treatment" in line 1. There is insufficient antecedent basis for this limitation in the claim as the prior recitation is to treating and culturing EPCs with PDGF-BB. As claimed, it is unclear whether the instantly recited “treatment” is intended to refer to treating and culturing of EPCs or a different treatment. Appropriate correction is required.
With regard to claim 22, the term “enhances vasculogenic activity” in lines 1-2 is subjective term which renders the claim indefinite. A claim may be rendered indefinite by reference to subjective term (see MPEP 2173.05(b), IV). The phrase “enhances vasculogenic activity” is not defined by the claim, the specification does not provide a standard for measuring the scope of the term, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Applicant has not defined what constitutes “vasculogenic activity”, particularly as claim 1 from which claim 22 depends already recites cells having increased vasculogenesis, or what is to be considered “enhanced”, thus rendering the scope of the claim indefinite. Appropriate correction is required.
Claim 23, which depends from claim 1, recites the limitation "treatment" in line 2. There is insufficient antecedent basis for this limitation in the claim as the prior recitation is to treating and culturing EPCs with PDGF-BB. As claimed, it is unclear whether the instantly recited “treatment” with PDGF-BB is intended to refer to treating and culturing of EPCs or a different treatment. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 1-3 and 19-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liang et al. (2017, Coculture of endothelial progenitor cells and mesenchymal stem cells enhanced their proliferation and angiogenesis through PDGF and Notch signaling. FEBS Open Bio, 7(11), 1722-1736, found in IDS dated 08/25/2023, hereafter “Liang”) and as evidenced by Sufen et al. (2011, bFGF and PDGF‐BB have a synergistic effect on the proliferation, migration and VEGF release of endothelial progenitor cells. Cell Bio. Intl., 35(5), 545-551, hereafter “Sufen”), Simon-Assmann et al. (2011, Role of laminins in physiological and pathological angiogenesis. Intl. J. of Dev. Bio., 55(4), 455, hereafter “Simon-Assmann”), Fang et al. (2019, Autologous endothelial progenitor cells transplantation for acute ischemic stroke: a 4-year follow-up study. Stem Cells Trans. Med., 8(1), 14-21, hereafter “Fang”), and Sorkin et al. (1991, Effect of receptor kinase inactivation on the rate of internalization and degradation of PDGF and the PDGF beta-receptor. J. of Cell Bio., 112(3), 469-478), hereafter “Sorkin”).
With regard to claim 1, Liang discloses culture of isolated EPCs (Pg. 1724, left col., 1st full para.) with PDGF-BB (Pg. 1724, right col., 1st para. and Fig. 2A) and that PDGF and Notch signaling pathways are critical for vasculogenesis (Pg. 1723, right col., 2nd para.). Liang discloses that culture with PDGF-BB increased PDGFR expression, a marker of increased PDGF signaling, (Fig. 2B and Fig. 5A) and Notch expression (Fig. 5A) in EPCs as well as in EPCs cocultured with mesenchymal stem cells (MSCs) (Figs 2A and 5A; Pg. 1726, left col., 1st full para.). Further, Liang discloses that culture with PDGF-BB increased the number and diameter of tubule formation in vitro (Pg. 1726, left col., last para. and Fig. 4), which is considered to reasonably read on increased vasculogenesis based on the definition of vasculogenesis as the process by which EPCs differentiate into mature endothelial cells which is provided in the instant specification (Pg. 1, last para.).
With regard to claim 2, Liang discloses use of human bone marrow derived EPCs (Abstract; Pg. 1724, left col., 1st full para.; and Pg. 1732, left col., 2nd and 3rd para.).
With regard to claims 3 and 20, MPEP 2111.04 (I) indicates that a “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure” and a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” The examiner has determined that the “wherein” clause of the instant claim does not limit the structure of the EPCs or the treatment of PDGF-BB as recited in the antecedent claims. Therefore, the language of the instant claim does not provide a limiting effect on the claimed method.
Furthermore, in regard to claim 3, which recites "wherein the endothelial progenitor cells … have increased cell migration, increased cell viability, increased cell proliferation, and increased expression of an extra-matrix protein laminin β1" and claim 20 which recites "wherein the treatment with PDGF-BB increases expression of an extra-matrix protein laminin β1", it is noted that these clauses do not recite any additional active method steps, but simply state a characterization or conclusion of the results of process step positively recited (e.g. treating). Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
As detailed above, Liang discloses that culture of EPCs with PDGF-BB results in EPCs having increased vasculogenesis. Liang discloses that EPCs cultured with PDGF-BB have enhanced cell proliferation (Pg. 1724, right col., 1st para.). This teaching is considered to reasonably read on EPCs having increased cell viability, as a skilled artisan would recognize that only viable cells are able to proliferate. Liang is silent as to EPCs cultured with PDGF-BB having increased migration and increased laminin β1 expression. Increased migration of EPCs appears to be an inherent outcome of treatment of EPCs with PDGF-BB as evidenced by Sufen. Sufen evidences that PDGF-BB promotes EPC proliferation (Abstract; Pg. 547, Section 3.2 and Fig. 2) and migration (Abstract; Pg. 547, Section 3.3 and Figs 3C and 4). Increased laminin β1 expression also appears to be an inherent outcome of increased vasculogenesis/angiogenesis in endothelial cells as evidenced by Simon-Assmann. Simon-Assmann evidences that the laminin α4 chain, which comprises laminin β1 in the form of laminin-411, is widely and exclusively expressed in developing microvessels and plays a role in angiogenesis and is associated with endothelial cell migration, tube formation, and proliferation (Pg. 460, right col., 1st full para.)
With regard to claim 19, MPEP 2111.04 (I) indicates that a “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure” and a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” The examiner has determined that the “wherein” clause of the instant claim does not limit the structure of the EPCs or the treatment of PDGF-BB as recited in the antecedent claims. Therefore, the language of the instant claim does not provide a limiting effect on the claimed method.
Furthermore, in regard to claim 19, it is noted that the " wherein the endothelial progenitor cells have a cell phenotype characterized by being negative for CD31, CD309, CD45, and CD34” clause does not recite any additional active method steps, but simply states a characterization or conclusion of the results of process step positively recited (e.g. treating). Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
As detailed above, Liang discloses that culture of EPCs with PDGF-BB results in EPCs having increased vasculogenesis. Liang’s EPCs are derived from mononuclear cells (MNCs) (Pg. 1732, left col., 2nd para.) from human bone marrow aspirate (Pg. 1732, left col., 1st para.), cultured in fibronectin coated dishes, and induced by EGM-2 (Pg. 1732, left col., 2nd para.). Applicant’s specification indicates that human bone marrow MSCs were cultured in collagen coated dishes in EGM-2 (Example 1.1). Thus, the EPCs of Liang and the instant invention appears to be comprise a mixed population of cells derived from the same origin and produced by the same methods and a skilled artisan could reasonably expect cells negative for CD31, CD309, CD45, and CD34 as instantly claimed would also exist in the population of cells as taught by Liang. Although Liang discloses that their bone marrow derived EPCs were positive for CD34, Liang also discloses that presence of CD34 decreases with time in culture (Pg. 1724, left col., 1st fill para.), which is a well known consequence of differentiation of EPCs during time in culture. Additionally, Fang evidences that bone marrow derived EPCs, cultured by the same method as Liang (Pg. 15, right col., 2nd full para.) were characterized as being CD34, CD31, and CD45 negative with some CD309 (i.e., KDR) expression (Pg. 17, right col., last para. and Supplementary Fig 1 at end). Based on Applicant’s instant disclosure, it appears that some CD309 expression is also present in Applicant’s disclosed EPCs (Specification Pg. 22, last para.).
With regard to claim 21, MPEP 2111.04 (I) indicates that a “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure” and a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” The examiner has determined that the “wherein” clause of the instant claim does not limit the structure of the EPCs or the treatment of PDGF-BB as recited in the antecedent claims. Therefore, the language of the instant claim does not provide a limiting effect on the claimed method.
Furthermore, in regard to claim 21, it is noted that the " wherein the treatment with PDGF-BB increases internalization of PDGFRβ” clause does not recite any additional active method steps, but simply states a characterization or conclusion of the results of process step positively recited (e.g. treating). Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
As detailed above, Liang teaches that culture of EPCs with PDGF-BB results in EPCs having increased vasculogenesis. Liang also teaches that the tyrosine kinase receptor PDGFRβ is expressed on EPCs (Pg. 1723, right col., 2nd para.) and that culture of EPCs with PDGF-BB increases PDGFRβ expression (Fig. 2B and Fig. 5A; Pg. 1733, Western Blot Analysis). Although Liang is silent as to increased internalization of PDGFRβ in EPCs, this appears to be an inherent outcome of binding between PDGFRβ and its ligand, PDGF-BB, as evidenced by Sorkin. Sorkin evidences that binding of PDGF-BB to PDGFRβ causes internalization of the receptor (Abstract, Pg. 469, left col., last para.).
With regard to claim 22, Liang discloses that treatment with PDGF-BB increases PDGFR expression (specifically PDGFRβ (See Pg. 1733, Western Blot Analysis)), a marker of increased PDGF signaling, (Fig. 2B and Fig. 5A) and Notch expression (Fig. 5A) in treated EPCs compared to untreated EPCs, which Liang discloses are signaling pathways critical for vasculogenesis (Pg. 1723, right col., 2nd para.). Liang also discloses that, in vitro, EPCs treated with PDGF-BB show increased number and diameter of tubule formation (Pg. 1726, left col., last para. and Fig. 4) compared to untreated EPCs, which is considered to reasonably read on increased vasculogenic activity.
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.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Liang as applied to claim 1 above and in view of Jianguo et al. (2010, Optimization of culture conditions for endothelial progenitor cells from porcine bone marrow in vitro. Cell Proliferation, 43(4), 418-426, hereafter “Jianguo”).
With regard to claim 18, as detailed above, Liang teaches that culture of isolated EPCs with PDGF-BB results in EPCs having increased vasculogenesis. Liang teaches that isolated EPCs exhibited vascular-like cells having spindle-shaped endothelium-like morphology on culture day 7 but assembled into clusters with cobblestone-like morphology on Day 14, which is indicative of a mature endothelial cell phenotype (Pg. 1724, left col. 1st full para. and Fig. 1A) and that first passage EPCs were used in for treatment of cultured EPCs with PDGF-BB (Pg. 1732, right col., first para.).
Liang does not teach use of second or third passaged EPCs.
Jianguo teaches optimization of culture conditions for bone marrow derived EPCs (Abstract) and that EPCs proliferated rapidly from passage one to passage four and reached a peak at three days in culture (Pgs. 43-44, “Expansion”). Jianguo further teaches that the cultured EPCs retain spindle-shaped morphology (Figure 1).
Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the instant invention, to choose EPCs which had been passaged two or three times based routine optimization in view of the teachings of Liang and Jianguo. Liang teaches use of less differentiated spindle shaped cells of the first passage of EPCs and their utility in cell-based therapy for tissue repair (Pg. 1723, left col., 1st para.). Jianguo also teaches that EPCs have been used in cell-based therapy for tissue repair (Pg. 418, right col., 2nd para.) and that EPCs rapidly proliferate between passages one and four and maintain spindle-shaped morphology. Therefore, based on the teachings of Jianguo that EPCs retain high proliferative ability from passage one to passage four and maintain their less-differentiated spindle shaped morphology, a skilled artisan could have easily envisioned use of EPCs which had been subcultured two to three passages in the method of Liang using EPCs at the first passage. One having ordinary skill in the art would have had a reasonable expectation of success as both Liang and Jianguo teach culture of bone marrow derived EPCs and that EPCs have utility in cell based therapies for tissue repair.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Liang as applied to claim 1 above in view of Jianguo, and as and as evidenced by Sorkin and Simon-Assmann.
With regard to claim 23, MPEP 2111.04 (I) indicates that a “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure” and a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” The examiner has determined that the “wherein” clause of the instant claim does not limit the treatment of PDGF-BB as recited in the antecedent claims. Therefore, the language of the instant claim does not provide a limiting effect on the claimed method.
Furthermore, in regard to claim 23, it is noted that the " wherein…the treatment with PDGF-BB increases expression of laminin β1 and internalization of PDGFRβ” clause does not recite any additional active method steps, but simply states a characterization or conclusion of the results of process step positively recited (e.g. treating). Therefore, the "wherein" clause is not considered to further limit the method defined by the claim and has not been given weight in construing the claims. See Texas Instruments, Inc. v. International Trade Comm., 988 F.2d 1165, 1171,26 USPQ2d 1018, 1023 (Fed Cir. 1993) ("A 'whereby' clause that merely states the result of the limitations in the claim adds nothing to the patentability or substance of the claim."). See also Minton v. National Assoc. of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003) ("A whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.").
As detailed above, Liang teaches that culture of isolated EPCs with PDGF-BB results in EPCs having increased vasculogenesis. Liang teaches that isolated EPCs exhibited vascular-like cells having spindle-shaped endothelium-like morphology on culture day 7 but assembled into clusters with cobblestone-like morphology on Day 14, which is indicative of a mature endothelial cell phenotype (Pg. 1724, left col. 1st full para. and Fig. 1A) and that first passage EPCs were used in for treatment of cultured EPCs with PDGF-BB (Pg. 1732, right col., first para.).
Liang does not teach use of second or third passaged EPCs.
Jianguo teaches optimization of culture conditions for bone marrow derived EPCs (Abstract) and that EPCs proliferated rapidly from passage one to passage four and reached a peak at three days in culture (Pgs. 43-44, “Expansion”). Jianguo further teaches that the cultured EPCs retain spindle-shaped morphology (Figure 1).
Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the instant invention, to choose EPCs which had been passaged two or three times based routine optimization in view of the teachings of Liang and Jianguo. Liang teaches use of less differentiated spindle shaped cells of the first passage of EPCs and their utility in cell-based therapy for tissue repair (Pg. 1723, left col., 1st para.). Jianguo also teaches that EPCs have been used in cell-based therapy for tissue repair (Pg. 418, right col., 2nd para.) and that EPCs rapidly proliferate between passages one and four and maintain spindle-shaped morphology. Therefore, based on the teachings of Jianguo that EPCs retain high proliferative ability from passage one to passage four and maintain their less-differentiated spindle shaped morphology, a skilled artisan could have easily envisioned use of EPCs which had been subcultured two to three passages in the method of Liang using EPCs at the first passage. One having ordinary skill in the art would have had a reasonable expectation of success as both Liang and Jianguo teach culture of bone marrow derived EPCs and that EPCs have utility in cell based therapies for tissue repair.
As detailed above in claim 21, Liang teaches that the tyrosine kinase receptor PDGFRβ is expressed on EPCs (Pg. 1723, right col., 2nd para.) and that culture of EPCs with PDGF-BB increases PDGFRβ expression (Fig. 2B and Fig. 5A; Pg. 1733, Western Blot Analysis). Although Liang is silent as to increased internalization of PDGFRβ in EPCs, this appears to be an inherent outcome of binding between PDGFRβ and its ligand, PDGF-BB, as evidenced by Sorkin. Sorkin evidences that binding of PDGF-BB to PDGFRβ causes internalization of the receptor (Abstract, Pg. 469, left col., last para.). As detailed above in claims 3 and 20, Liang teaches that culture of EPCs with PDGF-BB results in EPCs having increased vasculogenesis and enhanced cell proliferation (Pg. 1724, right col., 1st para.). Although Liang is silent as to increased laminin β1 expression, this also appears to be an inherent outcome of increased vasculogenesis/angiogenesis in endothelial cells as evidenced by Simon-Assmann. Simon-Assmann evidences that the laminin α4 chain, which comprises laminin β1 in the form of laminin-411, is widely and exclusively expressed in developing microvessels and plays a role in angiogenesis and is associated with endothelial cell migration, tube formation, and proliferation (Pg. 460, right col., 1st full para.) Therefore, a skilled artisan would have every reason to believe that PDGF-BB treatment of passage two or three EPCs as taught by the combination of Liang and Jianguo would inherently result in increased internalization of PDGFRβ as evidenced by Sorkin and increased laminin β1 expression as evidenced by Simon-Assmann
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERIN V PAULUS whose telephone number is (571)272-6301. The examiner can normally be reached Mon-Fri 8 AM-5 PM.
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, Doug Schultz can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERIN V PAULUS/Examiner, Art Unit 1631
/ARTHUR S LEONARD/Examiner, Art Unit 1631
Prosecution Insights