DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is responsive to papers filed 03/13/2026.
Claims 1 and 6 have been amended. No claims have been newly added or newly canceled.
Claims 1-19 are currently pending and have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 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.
Claim(s) 11-12, 14-19 remain rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Butler (US 2019/0224240-previously cited).
Regarding claims 11, 16-19, Butler disclose cell therapy for the treatment of non-ischemic heart failure (a patient in need of reduction of systemic inflammation) by administering mesenchymal stem cells through intravenous administration in an effective amount two or more times per day, per week, per month or per year wherein the effective amount is 1.5 x 106 (1.5 million) cells per kg body weight (abstract, page 4 para 69).
Regarding claims 12, 14-15, Butler disclose wherein the mesenchymal stem cells are derived from human tissue (page 4 para 66-67) including umbilical cord blood and bone marrow (pages 3-4, para 65-66).
Therefore, the teaching of Butler anticipates Applicant’s invention as claimed.
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 (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 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(s) 1-3, 5-7, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Bartolucci et al (Circulation Research 2017-newly cited).
Regarding claims 1 and 3, Bartolucci disclose methods of treating heart failure patients with intravenous (systemic) infusion of umbilical cord mesenchymal stem cells (Title, abstract, pages 1192-1194). Bartolucci disclose that this is a feasible treatment for ischemic and nonischemic heart failure and that the systemic administration simplifies therapy, decreases costs of the procedure, and allows exploration of repeated dosages (page 1193, What Information Does This Article Contribute?).
Regarding claim 2, Bartolucci disclose wherein the mesenchymal stem cells are derived from human tissue (page 1194, paragraph bridging columns 1-2).
Regarding claim 5, Bartolucci teach and suggest wherein bone marrow is an alternative source of the mesenchymal stem cells (BM-MSC)(abstract, page 1192-1193).
Regarding claim 6, Bartolucci disclose wherein the heart failure is chronic heart failure (page 1192 abstract, page 1193-1194).
Regarding claim 7, Bartolucci disclose intravenous delivery of the mesenchymal stem cells (UC-MSCs) (page 1194, 1198).
Regarding claim 10, Bartolucci disclose wherein a cell concentration of each dose is 1x106 cells/kg (page 1192 abstract, page 1194 column 2).
Bartolucci suggest that repeated dosages are to be explored (page 1193), and thus render obvious an embodiment with at least two doses that are administered separated by an interval of time.
The specific combination of features claimed is disclosed within the broad genera of types of heart failure and tissue sources for mesenchymal stem cells taught by Bartolucci, but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). Where, as here, the reference does not provide any specific teaching to select this specific combination of variables, anticipation cannot be found.
That being said, however, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to have selected treatment of ischemic heart failure, mesenchymal stem cells derived from various sources such as cord and marrow from within the disclosure of Butler to arrive at methods and compositions “yielding no more than one would expect from such an arrangement”.
The motivation and reasonable expectation of success in making these combinations comes from the fact that Bartolucci suggests that all these cited variables are suitable for inclusion in their method/composition.
Therefore, the teaching of Bartolucci renders obvious Applicant’s invention as claimed.
Claim(s) 1-8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Bartolucci et al (Circulation Research 2017-newly cited) as applied to claims 1-3, 5-7, and 10 above, and further in view of Silviu et al (KR 20170095932-machine translation-newly cited).
Regarding claims 1 and 3, Bartolucci disclose methods of treating heart failure patients with intravenous (systemic) infusion of umbilical cord mesenchymal stem cells (Title, abstract, pages 1192-1194). Bartolucci disclose that this is a feasible treatment for ischemic and nonischemic heart failure and that the systemic administration simplifies therapy, decreases costs of the procedure, and allows exploration of repeated dosages (page 1193, What Information Does This Article Contribute?).
Regarding claim 2, Bartolucci disclose wherein the mesenchymal stem cells are derived from human tissue (page 1194, paragraph bridging columns 1-2).
Regarding claim 5, Bartolucci teach and suggest wherein bone marrow is an alternative source of the mesenchymal stem cells (BM-MSC)(abstract, page 1192-1193).
Regarding claim 6, Bartolucci disclose wherein the heart failure is chronic heart failure (page 1192 abstract, page 1193-1194).
Regarding claim 7, Bartolucci disclose intravenous delivery of the mesenchymal stem cells (UC-MSCs) (page 1194, 1198).
Regarding claim 10, Bartolucci disclose wherein a cell concentration of each dose is 1x106 cells/kg (page 1192 abstract, page 1194 column 2).
Bartolucci suggest that repeated dosages are to be explored (page 1193), and thus render obvious an embodiment with at least two doses that are administered separated by an interval of time.
Silviu disclose methods of treating heart failure in a subject with a pharmaceutical composition containing mesenchymal stem cells (page 14). The heart failure occurs due to ischemic or non-ischemic factors (page 3) and the mesenchymal stem cells are found in the bone marrow as well as cord blood and umbilical cord tissue (page 5). Exemplary doses include about 1.5 x 106 cells/kg (page 15) and number of doses can be at least 2 to at least 10 doses and may be administered intravenously (page 17).
One of ordinary skill in the art would have been motivated to include at least 2 doses of the mesenchymal stem cells and up to 10 doses of the cells in the method of Bartolucci because Silviu teach and suggest that this is a suitable number of doses to administered of mesenchymal stem cells in a method of treating ischemic heart failure. One of ordinary skill in the art would have been motivated to use mesenchymal stem cells from cord blood as an alternative source in the method of Bartolucci because Silviu teach and suggest that mesenchymal stem cells from cord blood are an alternative to those from marrow and umbilical cord tissue. One of ordinary skill in the art would have been motivated to treat ischemic heart failure as the type of heart failure in the method of Bartolucci because Silviu teach and suggest that this is a type of heart failure that benefits from the administration of mesenchymal stem cells. One of ordinary skill in the art would have had a reasonable expectation of success because both Bartolucci and Silviu are drawn to the treatment of ischemic heart failure with intravenously administered mesenchymal stem cells and Bartolucci also suggest the desire to treat ischemic heart failure and to include repeated dosages in their method as well.
Therefore, the combined teachings of Bartolucci et al and Silviu et al render obvious Applicant’s invention as well.
Claim(s) 9 is rejected under 35 U.S.C. 103 as being unpatentable over Bartolucci et al (Circulation Research 2017-newly cited) in view of Silviu et al (KR 20170095932-machine translation-newly cited) as applied to claims 1-8 and 10 above, and further in view of Woods et al (US 2012/0052049-newly cited).
Regarding claim 9, Bartolucci in view of Silviu render obvious the method of claim 1 as described above, but are silent with regard to the interval of time in between repeated doses.
Woods disclose methods for treating diseases by providing therapeutic doses of mesenchymal stem cells through intravenous injection (abstract). The mesenchymal stem cells (MSCs) are derived from various tissues such as bone marrow, placental tissue and umbilical cord tissue (page 2 para 16) and used to treat diseases such as cardiomyopathy, myocardial infarction and congestive heart failure (page 2 para 17). The MSCs can comprise one or more doses and delivered at preselected time intervals such as weekly intervals or monthly intervals (page 2 para 12).
One of ordinary skill in the art would have been motivated to administer the repeated doses of mesenchymal stem cells in the method of Bartolucci at weekly or monthly intervals because Woods teach and suggest that these are suitable time intervals for the delivery of repeated doses of MSCs in the treatment of diseases. One of ordinary skill in the art would have had a reasonable expectation of success because both Bartolucci and Woods are drawn to the use of mesenchymal stem cells for the treatment of heart failure through intravenous injection.
Therefore, the combined teachings of Bartolucci et al, Silviu et al and Woods et al render obvious Applicant’s invention as well.
Claim(s) 11-19 remain rejected under 35 U.S.C. 103 as being unpatentable over Butler (US 2019/0224240-previously cited).
Regarding claims 11, 16-19, Butler disclose cell therapy for the treatment of non-ischemic heart failure (a patient in need of reduction of systemic inflammation) by administering mesenchymal stem cells through intravenous administration in an effective amount two or more times per day, per week, per month or per year wherein the effective amount is 1.5 x 106 (1.5 million) cells per kg body weight (abstract, page 4 para 69).
Regarding claims 12-13, 14-15, Butler disclose wherein the mesenchymal stem cells are derived from human tissue (page 4 para 66-67) including any tissue source capable of providing mesenchymal stem cells that produce a therapeutic effect including umbilical cord blood, placenta and bone marrow (pages 3-4, para 65-66).
The specific combination of features claimed is disclosed within the broad genera of tissue sources for mesenchymal stem cells taught by Butler, but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). Where, as here, the reference does not provide any specific teaching to select this specific combination of variables, anticipation cannot be found.
That being said, however, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have selected various combinations of mesenchymal stem cells derived from placenta tissue, umbilical cord blood and tissue and bone marrow from within the disclosure of Butler to arrive at methods and compositions “yielding no more than one would expect from such an arrangement”.
The motivation and reasonable expectation of success in making these combinations comes from the fact that Butler suggests that all these cited variables are suitable for inclusion in their method/composition.
Therefore, the teaching of Butler renders obvious Applicant’s invention as claimed.
Claim(s) 13 remains rejected under 35 U.S.C. 103 as being unpatentable over Butler (US 2019/0224240) as applied to claims 11-19 above, and further in view of Yamahara et al (US 2018/0362922).
Regarding claim 13, Butler discloses the claimed method as described above, but does not specifically teach administering mesenchymal stem cells derived from solid umbilical cord tissue.
However, Butler do disclose using mesenchymal stem cells from any tissue source capable of providing mesenchymal stem cells that produce a therapeutic effect including umbilical cord blood, placenta and bone marrow (pages 3-4, para 65-66).
Yamahara disclose a method of producing a mesenchymal stem cell composition for pharmaceutical use (Title, abstract) such as the treatment of inflammatory disorders including heart failure (page 15-16 para 186-188, page 17 para 197). Yamahara teach that mesenchymal stem cells exist in fetal appendage including the placenta and umbilical cord (page 1 para 2).
One of ordinary skill in the art would have been motivated to use umbilical cord tissue for obtaining mesenchymal stem cells in the method of Butler because Yamahara teach and suggest that this tissue is a suitable source for such cells for pharmaceutical use. One of ordinary skill in the art would have had a reasonable expectation of success because Butler disclose using mesenchymal stem cells from any tissue source capable of providing mesenchymal stem cells that produce a therapeutic effect including umbilical cord blood, placenta and bone marrow (pages 3-4, para 65-66) and Yamahara also indicate that their mesenchymal stem cells are suitable for treating inflammatory disorders such as heart failure.
Therefore, the combined teachings of Butler and Yamahara et al render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant's arguments filed 03/13/2026 have been fully considered but they are not persuasive.
Applicant argues that the Butler reference does not anticipate the claims because the rejection does not establish a prima facie case of anticipation as the limitations are not arranged or combined in the same way as Applicant’s claims. Applicant asserts that picking and choosing does not meet the requirement provided by the Federal Circuit and cannot be used to anticipate Applicant’s claims.
This is not found persuasive. The picking and choosing within the Butler reference was only with regard to the choice of umbilical cord tissue derived MSCs and this is why claim 13 was not included in the 102 rejection.
Applicant argues that Butler is drawn to the treatment of non-ischemic heart failure and the claims have been amended to only treat ischemic heart failure. Applicant asserts that the 102 and 103 rejections have been overcome by this amendment.
This is only found persuasive for claim 1 and the claims dependent upon claim 1 which have been amended to specifically require ischemic heart failure. Claims 11-19 are not limited to ischemic heart failure and thus the rejections of these claims remain as recited above.
Applicant argues that it is simply not enough to base answers to the questions of choosing limitations and why one of ordinary skill in the art would modify or combine those limitations with others within the same reference or in other prior art by searching the limitations found in Applicant’s claimed invention. Applicant asserts that it is not sufficient to find the claimed limitations in documents and then declare a prima facie case of obviousness. Applicant asserts that this is not sufficient for motivation or suggestion to choose and combine these limitations. Applicant argues that a prima facie case of obviousness has not been established for claims 3 and 13 as well.
This is not found persuasive. “When a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have selected various combinations of mesenchymal stem cells derived from placenta tissue, umbilical cord blood and tissue and bone marrow from within the disclosure of Butler to arrive at methods and compositions “yielding no more than one would expect from such an arrangement”.
The motivation and reasonable expectation of success in making these combinations comes from the fact that Butler suggests that all these cited variables are suitable for inclusion in their method/composition.
As for claim 13, the motivation and reasonable expectation of success for including these claim limitations was described in the 103 rejection.
One of ordinary skill in the art would have been motivated to use umbilical cord tissue for obtaining mesenchymal stem cells in the method of Butler because Yamahara teach and suggest that this tissue is a suitable source for such cells for pharmaceutical use. One of ordinary skill in the art would have had a reasonable expectation of success because Butler disclose using mesenchymal stem cells from any tissue source capable of providing mesenchymal stem cells that produce a therapeutic effect including umbilical cord blood, placenta and bone marrow (pages 3-4, para 65-66) and Yamahara also indicate that their mesenchymal stem cells are suitable for treating inflammatory disorders such as heart failure.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Barbash et al., “Systemic Delivery of Bone Marrow–Derived Mesenchymal Stem Cells to the Infarcted Myocardium Feasibility, Cell Migration, and Body Distribution”, Circulation, 2003, Vol. 108, pp. 863-868.
Bagno et al., “Mesenchymal Stem Cell-Based Therapy for Cardiovascular Disease: Progress and Challenges”, Molecular Therapy, 2018, Vol. 26 No 7, pp. 1610-1623.
Krause et al., “Intravenous Delivery of Autologous Mesenchymal Stem Cells Limits Infarct Size and Improves Left Ventricular Function in the Infarcted Porcine Heart”, Stem Cells and Development, 2007, Vol. 16, pp. 31-37.
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 LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631