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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/22/2026 has been entered.
Claim 1 has been amended. Claim 22 has been newly added and no claims have been newly canceled.
Claims 1 and 4-22 are currently pending.
Claims 15-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/05/2024.
Claims 1, 4-14, and 22 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Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment.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 § 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.
Claim 22 is 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.
Regarding claim 22, this claim is drawn to the composition of claim 1, but claim 1 is drawn to a method for preparing a composition. It is unclear if claim 22 is drawn to the method of claim 1 or just the composition. Therefore, the metes and bounds of the claim are unclear and the claim is indefinite.
Appropriate corrections is required.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 22 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 22 is drawn to the composition of claim 1, but claim 1 is drawn to a method for preparing a composition. Therefore claim 22 drawn only to the composition fails to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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) 1, 4-5, 7-13 and 22 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Jeffs et al (US 2014/0193379-from IDS filed 12/29/2022, hereinafter referred to as “Jeffs ‘379”).
Regarding claims 1, 4-5, 8-13 and 22, Jeffs ‘379 disclose a method for preparing a composition comprising a mesenchymal stem cell or a culture medium that has been in contact with the MSC and comprises one or more components of the MSC, comprising exposing the MSC to a prostacyclin ex vivo, wherein the prostacylin is treprostinil and at a concentration of 1.0 µg/mL and 10 µg/mL for at least 24 hours (within the claimed range pf 0.3 to 10 µg/mL) and isolating at least a portion of the conditioned medium of the MSC (page 13, Example 1, para 173-175). Conditioned medium contains exosomes (page 3 para 38).
While Jeffs 379 do not specifically describe wherein the exposure increases expression of an anti-inflammatory factors in the MSC by at least 30, Jeffs 379 do carry out the same method step of exposing the MSCs to a prostacyclin ex vivo and therefore inherently include the effect of such exposure with regard to anti-inflammatory factors and the expression level of any other factors including the expression of exosomes, microvesicles, etc.. It is not required that a reference acknowledge the source or mechanism of all the effects of their method in order for inherency to be present.
Providing guidance on instances where the method steps of the prior art and instant claims are the same, Ex parte Marhold, 231 USPQ 904, 905 (Bd. Pat. App. & Int. 1986) relying on In re Sussman, 141 F.2d 267, 269-70, 60 USPQ 538, 540-41 (CCPA 1944) states “[T]hat since the steps are the same, the results must inherently be the same unless they are due to conditions not recited in the claims.”
Regarding claim 7, Jeffs ‘379 disclose wherein the MSC is exposed to the prostacylin post-expansion (page 13, Example 1, para 173-175).
Therefore, the teaching of Jeffs et al (Jeffs ‘379) 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) 6 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Jeffs et al (US 2014/0193379-from IDS filed 12/29/2022, hereinafter referred to as “Jeffs ‘379”).
Regarding claims 6 and 14, Jeffs ‘379 disclose a method for preparing a composition comprising a mesenchymal stem cell or a culture medium that has been in contact with the MSC and comprises one or more components of the MSC, comprising exposing the MSC to a prostacyclin ex vivo, wherein the prostacylin is treprostinil and at a concentration of 1.0 µg/mL and 10 µg/mL for at least 24 hours (within the claimed range pf 0.3 to 10 µg/mL) and isolating at least a portion of the conditioned medium of the MSC (page 13, Example 1, para 173-175). Conditioned medium contains exosomes (page 3 para 38).
Jeffs ‘379 do not specifically disclose wherein the MSC is exposed to the prostacylin for at least 48 hours or further isolating an exosome from the culture medium from this particular embodiment.
Jeffs ‘379 do indicate that the exposure can be during expansion of the MSCs (page 13, para 173) and that culture times to reinitiate proliferation of other cells can be for 3-7 days (at least 24 and 48 hours) (page 9 para 123), therefore one of ordinary skill in the art would have been motivated to expand the MSCs while exposed to prostacyclin for around 3-7 days or at least 24/48 hours in order to produce sufficient cell and/or exosome numbers for further analysis of the effect. One of ordinary skill in the art would have had a reasonable expectation of success because Jeffs indicated that culturing cells for 3-7 days, or at least 48 hours, was a suitable time period to reinitiate proliferation of cells intended for administration for therapeutic treatments of vasculopathy. Jeffs ‘379 also indicate that it is desirable to isolate and analyze exosomes for the effects of prostacyclin on the exosomes secreted after MSC contact with prostacyclin (page 14 para 188, Table 1, para 192, pages 18-19 para 198-199) providing further motivation and a reasonable expectation of success.
Therefore, the teaching of Jeffs et al (Jeffs 379) renders obvious Applicant’s invention as claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4-14 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10,071,123 in view of Davidson et al (US 2008/0187494-newly cited) and Jeffs et al (US 2014/0193379-from IDS filed 12/29/2022, hereinafter referred to as “Jeffs ‘379”).
The claims of the patent are drawn a pharmaceutical composition prepared by exposing MSCs to treprostinil (prostacyclin) and will inherently include those properties produced by such as exposure as described above.
The claims are silent with regard to the concentration of prostacyclin used and the time for expansion of the MSCs.
Davidson teach a method of inducing or enhancing the induction of differentiation of stem cells for therapeutic purposes (page 7 para 106) by culturing the cells in contact with a culture medium with a prostaglandin or its analogue or functional equivalent (page 6 para 92). The prostaglandin is P12 (aka prostacyclin- para 75) and is preferably used at a concentration of 20 nM (page 6 para 90) and the stem cells include MSCs (page 4 para 53).
A concentration of 20 nM prostacyclin is equivalent to approximately 7.81 µg/mL (the molecular weight of prostacyclin is approximately 390.51 g/mL, 20 nM x 390.51/1000= 7.81 µg/mL).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to use a prostacyclin concentration of about 20 nM (approximately 7.81 µg/mL) in the invention of the patent claims because Davidson indicate that this is a preferred concentration to use when exposing stem cells, such as MSCs, to prostacyclin for purposes of providing a pharmaceutical composition for therapeutic purposes.
The patent claims do not specifically include the collection of a conditioned medium with exosomes from the contacted MSCs, however isolation of exosomes from the conditioned medium for further analysis is well known in the prior art as taught and suggested by Jeffs ‘379.
Jeffs ‘379 disclose a method for preparing a composition comprising a mesenchymal stem cell or a culture medium that has been in contact with the MSC and comprises one or more components of the MSC, comprising exposing the MSC to a prostacyclin ex vivo, wherein the prostacylin is treprostinil and at a concentration of 1.0 µg/mL and 10 µg/mL for at least 24 hours (within the claimed range pf 0.3 to 10 µg/mL) and isolating at least a portion of the conditioned medium of the MSC (page 13, Example 1, para 173-175). Conditioned medium contains exosomes (page 3 para 38).
Jeffs ‘379 do not specifically disclose wherein the MSC is exposed to the prostacylin for at least 48 hours or further isolating an exosome from the culture medium from this particular embodiment.
Jeffs ‘379 do indicate that the exposure can be during expansion of the MSCs (page 13, para 173) and that culture times to reinitiate proliferation of other cells can be for 3-7 days (at least 24 and 48 hours) (page 9 para 123), therefore one of ordinary skill in the art would have been motivated to expand the MSCs while exposed to prostacyclin for around 3-7 days or at least 24/48 hours in order to produce sufficient cell and/or exosome numbers for further analysis of the effect. One of ordinary skill in the art would have had a reasonable expectation of success because Jeffs indicated that culturing cells for 3-7 days, or at least 48 hours, was a suitable time period to reinitiate proliferation of cells intended for administration for therapeutic treatments of vasculopathy. Jeffs ‘379 also indicate that it is desirable to isolate and analyze exosomes for the effects of prostacyclin on the exosomes secreted after MSC contact with prostacyclin (page 14 para 188, Table 1, para 192, pages 18-19 para 198-199) providing further motivation and a reasonable expectation of success.
Therefore, the combined teachings of the patent claims, Davidson et al and Jeffs et al (Jeffs ‘379) render obvious Applicant’s invention as claimed.
Claims 1, 4-14 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-7, 9-11 of U.S. Patent No. 10,080,730 in view of Davidson et al (US 2008/0187494-newly cited) and Jeffs et al (US 2014/0193379-from IDS filed 12/29/2022, hereinafter referred to as “Jeffs ‘379”).
The claims of the patent are drawn a pharmaceutical composition prepared by exposing MSCs to treprostinil (prostacyclin) and method of preparation and will inherently include those properties produced by such as exposure as described above.
The claims are silent with regard to the concentration of prostacyclin used and the time for expansion of the MSCs.
Davidson teach a method of inducing or enhancing the induction of differentiation of stem cells for therapeutic purposes (page 7 para 106) by culturing the cells in contact with a culture medium with a prostaglandin or its analogue or functional equivalent (page 6 para 92). The prostaglandin is P12 (aka prostacyclin- para 75) and is preferably used at a concentration of 20 nM (page 6 para 90) and the stem cells include MSCs (page 4 para 53).
A concentration of 20 nM prostacyclin is equivalent to approximately 7.81 µg/mL (the molecular weight of prostacyclin is approximately 390.51 g/mL, 20 nM x 390.51/1000= 7.81 µg/mL).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to use a prostacyclin concentration of about 20 nM (approximately 7.81 µg/mL) in the invention of the patent claims because Davidson indicate that this is a preferred concentration to use when exposing stem cells, such as MSCs, to prostacyclin for purposes of providing a pharmaceutical composition for therapeutic purposes.
The patent claims do not specifically include the collection of a conditioned medium with exosomes from the contacted MSCs, however isolation of exosomes from the conditioned medium for further analysis is well known in the prior art as taught and suggested by Jeffs ‘379.
Jeffs ‘379 disclose a method for preparing a composition comprising a mesenchymal stem cell or a culture medium that has been in contact with the MSC and comprises one or more components of the MSC, comprising exposing the MSC to a prostacyclin ex vivo, wherein the prostacylin is treprostinil and at a concentration of 1.0 µg/mL and 10 µg/mL for at least 24 hours (within the claimed range pf 0.3 to 10 µg/mL) and isolating at least a portion of the conditioned medium of the MSC (page 13, Example 1, para 173-175). Conditioned medium contains exosomes (page 3 para 38).
Jeffs ‘379 do not specifically disclose wherein the MSC is exposed to the prostacylin for at least 48 hours or further isolating an exosome from the culture medium from this particular embodiment.
Jeffs ‘379 do indicate that the exposure can be during expansion of the MSCs (page 13, para 173) and that culture times to reinitiate proliferation of other cells can be for 3-7 days (at least 24 and 48 hours) (page 9 para 123), therefore one of ordinary skill in the art would have been motivated to expand the MSCs while exposed to prostacyclin for around 3-7 days or at least 24/48 hours in order to produce sufficient cell and/or exosome numbers for further analysis of the effect. One of ordinary skill in the art would have had a reasonable expectation of success because Jeffs indicated that culturing cells for 3-7 days, or at least 48 hours, was a suitable time period to reinitiate proliferation of cells intended for administration for therapeutic treatments of vasculopathy. Jeffs ‘379 also indicate that it is desirable to isolate and analyze exosomes for the effects of prostacyclin on the exosomes secreted after MSC contact with prostacyclin (page 14 para 188, Table 1, para 192, pages 18-19 para 198-199) providing further motivation and a reasonable expectation of success.
Therefore, the combined teachings of the patent claims, Davidson et al and Jeffs et al (Jeffs ‘379) render obvious Applicant’s invention as claimed.
Claims 1, 4-14 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-10 of U.S. Patent No. 11,141,393 in view of Davidson et al (US 2008/0187494-newly cited) and Jeffs et al (US 2014/0193379-from IDS filed 12/29/2022, hereinafter referred to as “Jeffs ‘379”).
The claims of the patent are drawn a composition prepared by exposing MSCs to treprostinil (prostacyclin) and will inherently include those properties produced by such as exposure as described above.
The claims are silent with regard to the concentration of prostacyclin used and the time for expansion of the MSCs.
Davidson teach a method of inducing or enhancing the induction of differentiation of stem cells for therapeutic purposes (page 7 para 106) by culturing the cells in contact with a culture medium with a prostaglandin or its analogue or functional equivalent (page 6 para 92). The prostaglandin is P12 (aka prostacyclin- para 75) and is preferably used at a concentration of 20 nM (page 6 para 90) and the stem cells include MSCs (page 4 para 53).
A concentration of 20 nM prostacyclin is equivalent to approximately 7.81 µg/mL (the molecular weight of prostacyclin is approximately 390.51 g/mL, 20 nM x 390.51/1000= 7.81 µg/mL).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to use a prostacyclin concentration of about 20 nM (approximately 7.81 µg/mL) in the invention of the patent claims because Davidson indicate that this is a preferred concentration to use when exposing stem cells, such as MSCs, to prostacyclin for purposes of providing a pharmaceutical composition for therapeutic purposes.
The patent claims do not specifically include the collection of a conditioned medium with exosomes from the contacted MSCs, however isolation of exosomes from the conditioned medium for further analysis is well known in the prior art as taught and suggested by Jeffs ‘379.
Jeffs ‘379 disclose a method for preparing a composition comprising a mesenchymal stem cell or a culture medium that has been in contact with the MSC and comprises one or more components of the MSC, comprising exposing the MSC to a prostacyclin ex vivo, wherein the prostacylin is treprostinil and at a concentration of 1.0 µg/mL and 10 µg/mL for at least 24 hours (within the claimed range pf 0.3 to 10 µg/mL) and isolating at least a portion of the conditioned medium of the MSC (page 13, Example 1, para 173-175). Conditioned medium contains exosomes (page 3 para 38).
Jeffs ‘379 do not specifically disclose wherein the MSC is exposed to the prostacylin for at least 48 hours or further isolating an exosome from the culture medium from this particular embodiment.
Jeffs ‘379 do indicate that the exposure can be during expansion of the MSCs (page 13, para 173) and that culture times to reinitiate proliferation of other cells can be for 3-7 days (at least 24 and 48 hours) (page 9 para 123), therefore one of ordinary skill in the art would have been motivated to expand the MSCs while exposed to prostacyclin for around 3-7 days or at least 24/48 hours in order to produce sufficient cell and/or exosome numbers for further analysis of the effect. One of ordinary skill in the art would have had a reasonable expectation of success because Jeffs indicated that culturing cells for 3-7 days, or at least 48 hours, was a suitable time period to reinitiate proliferation of cells intended for administration for therapeutic treatments of vasculopathy. Jeffs ‘379 also indicate that it is desirable to isolate and analyze exosomes for the effects of prostacyclin on the exosomes secreted after MSC contact with prostacyclin (page 14 para 188, Table 1, para 192, pages 18-19 para 198-199) providing further motivation and a reasonable expectation of success.
Therefore, the combined teachings of the patent claims, Davidson et al and Jeffs et al (Jeffs ‘379) render obvious Applicant’s invention as claimed.
Claims 1, 4-14 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-12, 14-20 of U.S. Patent No. 11,666,602 in view of Davidson et al (US 2008/0187494-newly cited) and Jeffs et al (US 2014/0193379-from IDS filed 12/29/2022, hereinafter referred to as “Jeffs ‘379”).
The claims of the patent are drawn a composition prepared by exposing MSCs to treprostinil (prostacyclin) and will inherently include those properties produced by such as exposure as described above.
The claims are silent with regard to the concentration of prostacyclin used and the time for expansion of the MSCs.
Davidson teach a method of inducing or enhancing the induction of differentiation of stem cells for therapeutic purposes (page 7 para 106) by culturing the cells in contact with a culture medium with a prostaglandin or its analogue or functional equivalent (page 6 para 92). The prostaglandin is P12 (aka prostacyclin- para 75) and is preferably used at a concentration of 20 nM (page 6 para 90) and the stem cells include MSCs (page 4 para 53).
A concentration of 20 nM prostacyclin is equivalent to approximately 7.81 µg/mL (the molecular weight of prostacyclin is approximately 390.51 g/mL, 20 nM x 390.51/1000= 7.81 µg/mL).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to use a prostacyclin concentration of about 20 nM (approximately 7.81 µg/mL) in the invention of the patent claims because Davidson indicate that this is a preferred concentration to use when exposing stem cells, such as MSCs, to prostacyclin for purposes of providing a pharmaceutical composition for therapeutic purposes.
The patent claims do not specifically include the collection of a conditioned medium with exosomes from the contacted MSCs, however isolation of exosomes from the conditioned medium for further analysis is well known in the prior art as taught and suggested by Jeffs ‘379.
Jeffs ‘379 disclose a method for preparing a composition comprising a mesenchymal stem cell or a culture medium that has been in contact with the MSC and comprises one or more components of the MSC, comprising exposing the MSC to a prostacyclin ex vivo, wherein the prostacylin is treprostinil and at a concentration of 1.0 µg/mL and 10 µg/mL for at least 24 hours (within the claimed range pf 0.3 to 10 µg/mL) and isolating at least a portion of the conditioned medium of the MSC (page 13, Example 1, para 173-175). Conditioned medium contains exosomes (page 3 para 38).
Jeffs ‘379 do not specifically disclose wherein the MSC is exposed to the prostacylin for at least 48 hours or further isolating an exosome from the culture medium from this particular embodiment.
Jeffs ‘379 do indicate that the exposure can be during expansion of the MSCs (page 13, para 173) and that culture times to reinitiate proliferation of other cells can be for 3-7 days (at least 24 and 48 hours) (page 9 para 123), therefore one of ordinary skill in the art would have been motivated to expand the MSCs while exposed to prostacyclin for around 3-7 days or at least 24/48 hours in order to produce sufficient cell and/or exosome numbers for further analysis of the effect. One of ordinary skill in the art would have had a reasonable expectation of success because Jeffs indicated that culturing cells for 3-7 days, or at least 48 hours, was a suitable time period to reinitiate proliferation of cells intended for administration for therapeutic treatments of vasculopathy. Jeffs ‘379 also indicate that it is desirable to isolate and analyze exosomes for the effects of prostacyclin on the exosomes secreted after MSC contact with prostacyclin (page 14 para 188, Table 1, para 192, pages 18-19 para 198-199) providing further motivation and a reasonable expectation of success.
Therefore, the combined teachings of the patent claims, Davidson et al and Jeffs et al (Jeffs ‘379) render obvious Applicant’s invention as claimed.
Claims 1, 4-14 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,839,596 in view of Davidson et al (US 2008/0187494-newly cited) and Jeffs et al (US 2014/0193379-from IDS filed 12/29/2022, hereinafter referred to as “Jeffs ‘379”).
The claims of the patent are drawn a pharmaceutical composition prepared by exposing MSCs to treprostinil (prostacyclin) and will inherently include those properties produced by such as exposure as described above.
The claims are silent with regard to the concentration of prostacyclin used and the time for expansion of the MSCs.
Davidson teach a method of inducing or enhancing the induction of differentiation of stem cells for therapeutic purposes (page 7 para 106) by culturing the cells in contact with a culture medium with a prostaglandin or its analogue or functional equivalent (page 6 para 92). The prostaglandin is P12 (aka prostacyclin- para 75) and is preferably used at a concentration of 20 nM (page 6 para 90) and the stem cells include MSCs (page 4 para 53).
A concentration of 20 nM prostacyclin is equivalent to approximately 7.81 µg/mL (the molecular weight of prostacyclin is approximately 390.51 g/mL, 20 nM x 390.51/1000= 7.81 µg/mL).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to use a prostacyclin concentration of about 20 nM (approximately 7.81 µg/mL) in the invention of the patent claims because Davidson indicate that this is a preferred concentration to use when exposing stem cells, such as MSCs, to prostacyclin for purposes of providing a pharmaceutical composition for therapeutic purposes.
The patent claims do not specifically include the collection of a conditioned medium with exosomes from the contacted MSCs, however isolation of exosomes from the conditioned medium for further analysis is well known in the prior art as taught and suggested by Jeffs ‘379.
Jeffs ‘379 disclose a method for preparing a composition comprising a mesenchymal stem cell or a culture medium that has been in contact with the MSC and comprises one or more components of the MSC, comprising exposing the MSC to a prostacyclin ex vivo, wherein the prostacylin is treprostinil and at a concentration of 1.0 µg/mL and 10 µg/mL for at least 24 hours (within the claimed range pf 0.3 to 10 µg/mL) and isolating at least a portion of the conditioned medium of the MSC (page 13, Example 1, para 173-175). Conditioned medium contains exosomes (page 3 para 38).
Jeffs ‘379 do not specifically disclose wherein the MSC is exposed to the prostacylin for at least 48 hours or further isolating an exosome from the culture medium from this particular embodiment.
Jeffs ‘379 do indicate that the exposure can be during expansion of the MSCs (page 13, para 173) and that culture times to reinitiate proliferation of other cells can be for 3-7 days (at least 24 and 48 hours) (page 9 para 123), therefore one of ordinary skill in the art would have been motivated to expand the MSCs while exposed to prostacyclin for around 3-7 days or at least 24/48 hours in order to produce sufficient cell and/or exosome numbers for further analysis of the effect. One of ordinary skill in the art would have had a reasonable expectation of success because Jeffs indicated that culturing cells for 3-7 days, or at least 48 hours, was a suitable time period to reinitiate proliferation of cells intended for administration for therapeutic treatments of vasculopathy. Jeffs ‘379 also indicate that it is desirable to isolate and analyze exosomes for the effects of prostacyclin on the exosomes secreted after MSC contact with prostacyclin (page 14 para 188, Table 1, para 192, pages 18-19 para 198-199) providing further motivation and a reasonable expectation of success.
Therefore, the combined teachings of the patent claims, Davidson et al and Jeffs et al (Jeffs ‘379) render obvious Applicant’s invention as claimed.
Claims 1, 4-14 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,839,631 in view of Davidson et al (US 2008/0187494-newly cited) and Jeffs et al (US 2014/0193379-from IDS filed 12/29/2022, hereinafter referred to as “Jeffs ‘379”).
The claims of the patent are drawn a composition prepared by exposing MSCs to treprostinil (prostacyclin) and will inherently include those properties produced by such as exposure as described above.
The claims are silent with regard to the concentration of prostacyclin used and the time for expansion of the MSCs.
Davidson teach a method of inducing or enhancing the induction of differentiation of stem cells for therapeutic purposes (page 7 para 106) by culturing the cells in contact with a culture medium with a prostaglandin or its analogue or functional equivalent (page 6 para 92). The prostaglandin is P12 (aka prostacyclin- para 75) and is preferably used at a concentration of 20 nM (page 6 para 90) and the stem cells include MSCs (page 4 para 53).
A concentration of 20 nM prostacyclin is equivalent to approximately 7.81 µg/mL (the molecular weight of prostacyclin is approximately 390.51 g/mL, 20 nM x 390.51/1000= 7.81 µg/mL).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to use a prostacyclin concentration of about 20 nM (approximately 7.81 µg/mL) in the invention of the patent claims because Davidson indicate that this is a preferred concentration to use when exposing stem cells, such as MSCs, to prostacyclin for purposes of providing a pharmaceutical composition for therapeutic purposes.
The patent claims do not specifically include the collection of a conditioned medium with exosomes from the contacted MSCs, however isolation of exosomes from the conditioned medium for further analysis is well known in the prior art as taught and suggested by Jeffs ‘379.
Jeffs ‘379 disclose a method for preparing a composition comprising a mesenchymal stem cell or a culture medium that has been in contact with the MSC and comprises one or more components of the MSC, comprising exposing the MSC to a prostacyclin ex vivo, wherein the prostacylin is treprostinil and at a concentration of 1.0 µg/mL and 10 µg/mL for at least 24 hours (within the claimed range pf 0.3 to 10 µg/mL) and isolating at least a portion of the conditioned medium of the MSC (page 13, Example 1, para 173-175). Conditioned medium contains exosomes (page 3 para 38).
Jeffs ‘379 do not specifically disclose wherein the MSC is exposed to the prostacylin for at least 48 hours or further isolating an exosome from the culture medium from this particular embodiment.
Jeffs ‘379 do indicate that the exposure can be during expansion of the MSCs (page 13, para 173) and that culture times to reinitiate proliferation of other cells can be for 3-7 days (at least 24 and 48 hours) (page 9 para 123), therefore one of ordinary skill in the art would have been motivated to expand the MSCs while exposed to prostacyclin for around 3-7 days or at least 24/48 hours in order to produce sufficient cell and/or exosome numbers for further analysis of the effect. One of ordinary skill in the art would have had a reasonable expectation of success because Jeffs indicated that culturing cells for 3-7 days, or at least 48 hours, was a suitable time period to reinitiate proliferation of cells intended for administration for therapeutic treatments of vasculopathy. Jeffs ‘379 also indicate that it is desirable to isolate and analyze exosomes for the effects of prostacyclin on the exosomes secreted after MSC contact with prostacyclin (page 14 para 188, Table 1, para 192, pages 18-19 para 198-199) providing further motivation and a reasonable expectation of success.
Therefore, the combined teachings of the patent claims, Davidson et al and Jeffs et al (Jeffs ‘379) render obvious Applicant’s invention as claimed.
Claims 1, 4-14 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 12,274,684 in view of Davidson et al (US 2008/0187494-newly cited) and Jeffs et al (US 2014/0193379-from IDS filed 12/29/2022, hereinafter referred to as “Jeffs ‘379”).
The claims of the patent are drawn a pharmaceutical composition prepared by exposing MSCs to treprostinil (prostacyclin) and will inherently include those properties produced by such as exposure as described above.
The claims are silent with regard to the concentration of prostacyclin used and the time for expansion of the MSCs.
Davidson teach a method of inducing or enhancing the induction of differentiation of stem cells for therapeutic purposes (page 7 para 106) by culturing the cells in contact with a culture medium with a prostaglandin or its analogue or functional equivalent (page 6 para 92). The prostaglandin is P12 (aka prostacyclin- para 75) and is preferably used at a concentration of 20 nM (page 6 para 90) and the stem cells include MSCs (page 4 para 53).
A concentration of 20 nM prostacyclin is equivalent to approximately 7.81 µg/mL (the molecular weight of prostacyclin is approximately 390.51 g/mL, 20 nM x 390.51/1000= 7.81 µg/mL).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to use a prostacyclin concentration of about 20 nM (approximately 7.81 µg/mL) in the invention of the patent claims because Davidson indicate that this is a preferred concentration to use when exposing stem cells, such as MSCs, to prostacyclin for purposes of providing a pharmaceutical composition for therapeutic purposes.
The patent claims do not specifically include the collection of a conditioned medium with exosomes from the contacted MSCs, however isolation of exosomes from the conditioned medium for further analysis is well known in the prior art as taught and suggested by Jeffs ‘379.
Jeffs ‘379 disclose a method for preparing a composition comprising a mesenchymal stem cell or a culture medium that has been in contact with the MSC and comprises one or more components of the MSC, comprising exposing the MSC to a prostacyclin ex vivo, wherein the prostacylin is treprostinil and at a concentration of 1.0 µg/mL and 10 µg/mL for at least 24 hours (within the claimed range pf 0.3 to 10 µg/mL) and isolating at least a portion of the conditioned medium of the MSC (page 13, Example 1, para 173-175). Conditioned medium contains exosomes (page 3 para 38).
Jeffs ‘379 do not specifically disclose wherein the MSC is exposed to the prostacylin for at least 48 hours or further isolating an exosome from the culture medium from this particular embodiment.
Jeffs ‘379 do indicate that the exposure can be during expansion of the MSCs (page 13, para 173) and that culture times to reinitiate proliferation of other cells can be for 3-7 days (at least 24 and 48 hours) (page 9 para 123), therefore one of ordinary skill in the art would have been motivated to expand the MSCs while exposed to prostacyclin for around 3-7 days or at least 24/48 hours in order to produce sufficient cell and/or exosome numbers for further analysis of the effect. One of ordinary skill in the art would have had a reasonable expectation of success because Jeffs indicated that culturing cells for 3-7 days, or at least 48 hours, was a suitable time period to reinitiate proliferation of cells intended for administration for therapeutic treatments of vasculopathy. Jeffs ‘379 also indicate that it is desirable to isolate and analyze exosomes for the effects of prostacyclin on the exosomes secreted after MSC contact with prostacyclin (page 14 para 188, Table 1, para 192, pages 18-19 para 198-199) providing further motivation and a reasonable expectation of success.
Therefore, the combined teachings of the patent claims, Davidson et al and Jeffs et al (Jeffs ‘379) render obvious Applicant’s invention as claimed.
Claims 1, 4-14 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,310,992 in view of Davidson et al (US 2008/0187494-newly cited) and Jeffs et al (US 2014/0193379-from IDS filed 12/29/2022, hereinafter referred to as “Jeffs ‘379”).
The claims of the patent are drawn a pharmaceutical composition prepared by exposing MSCs to treprostinil (prostacyclin) and will inherently include those properties produced by such as exposure as described above.
The claims are silent with regard to the concentration of prostacyclin used and the time for expansion of the MSCs.
Davidson teach a method of inducing or enhancing the induction of differentiation of stem cells for therapeutic purposes (page 7 para 106) by culturing the cells in contact with a culture medium with a prostaglandin or its analogue or functional equivalent (page 6 para 92). The prostaglandin is P12 (aka prostacyclin- para 75) and is preferably used at a concentration of 20 nM (page 6 para 90) and the stem cells include MSCs (page 4 para 53).
A concentration of 20 nM prostacyclin is equivalent to approximately 7.81 µg/mL (the molecular weight of prostacyclin is approximately 390.51 g/mL, 20 nM x 390.51/1000= 7.81 µg/mL).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to use a prostacyclin concentration of about 20 nM (approximately 7.81 µg/mL) in the invention of the patent claims because Davidson indicate that this is a preferred concentration to use when exposing stem cells, such as MSCs, to prostacyclin for purposes of providing a pharmaceutical composition for therapeutic purposes.
The patent claims do not specifically include the collection of a conditioned medium with exosomes from the contacted MSCs, however isolation of exosomes from the conditioned medium for further analysis is well known in the prior art as taught and suggested by Jeffs ‘379.
Jeffs ‘379 disclose a method for preparing a composition comprising a mesenchymal stem cell or a culture medium that has been in contact with the MSC and comprises one or more components of the MSC, comprising exposing the MSC to a prostacyclin ex vivo, wherein the prostacylin is treprostinil and at a concentration of 1.0 µg/mL and 10 µg/mL for at least 24 hours (within the claimed range pf 0.3 to 10 µg/mL) and isolating at least a portion of the conditioned medium of the MSC (page 13, Example 1, para 173-175). Conditioned medium contains exosomes (page 3 para 38).
Jeffs ‘379 do not specifically disclose wherein the MSC is exposed to the prostacylin for at least 48 hours or further isolating an exosome from the culture medium from this particular embodiment.
Jeffs ‘379 do indicate that the exposure can be during expansion of the MSCs (page 13, para 173) and that culture times to reinitiate proliferation of other cells can be for 3-7 days (at least 24 and 48 hours) (page 9 para 123), therefore one of ordinary skill in the art would have been motivated to expand the MSCs while exposed to prostacyclin for around 3-7 days or at least 24/48 hours in order to produce sufficient cell and/or exosome numbers for further analysis of the effect. One of ordinary skill in the art would have had a reasonable expectation of success because Jeffs indicated that culturing cells for 3-7 days, or at least 48 hours, was a suitable time period to reinitiate proliferation of cells intended for administration for therapeutic treatments of vasculopathy. Jeffs ‘379 also indicate that it is desirable to isolate and analyze exosomes for the effects of prostacyclin on the exosomes secreted after MSC contact with prostacyclin (page 14 para 188, Table 1, para 192, pages 18-19 para 198-199) providing further motivation and a reasonable expectation of success.
Therefore, the combined teachings of the patent claims, Davidson et al and Jeffs et al (Jeffs ‘379) render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1, 4-14 and 22 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Junichi et al “Method for Induction of Proliferation/Differentiation of Endothelial Progenitor Cell (EPC)”, (JP-2011015609-A and machine translation).
Junichi disclose concentrations of prostacylin of 1 to 10 nM and the increase of the cell secretion of eNOS (anti-inflammatory factor) from treated cells.
Davidson et al (Cardiomyocyte Production” (WO 2007/030870).
Davidson disclose concentrations of prostacylin of 20 nM for use with stem cells such as MSCs.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/ Primary Examiner, Art Unit 1631
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