DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 17-20) in the reply filed on 03/20/2025 is acknowledged.
Claims 17-21 are currently pending.
Claim 21 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 03/20/2025.
Claims 17-20 have been examined on their merits.
Claim Interpretation
Regarding claim 17, the claim requires administering a composition comprising a population of MSCs and blebbistatin, wherein the population of MSCs and the blebbistatin are incubated together for a period of time prior to the administration to a patient.
The claim does not require a specific length of time for the incubation period and as such once the MSCs and the blebbistatin are brought into contact in a composition prior to administration an incubation period is deemed to be present. This is supported by Applicant’s disclosure which indicates that an incubation period can be about, at least, or more than 0.1 minutes, hours or days prior to administration (page 23 paragraph 85 of Applicant’s Specification). An incubation of about 0.1 minutes is equal to about 6 seconds and deemed to be easily arrived at through ordinary mixing or contact.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 17-20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lu et al (Diabetes Research and Clinical Practice, 2011-from IDS filed 08/14/2024) in view of Martin-Rendon et al (WO 2011/135380-from IDS filed 08/14/2024), Singh et al (WO 2012/177880-from IDS filed 08/14/2024) and Schenk et al (WO 2012/062819-from IDS filed 08/14/2024).
Regarding claim 17, Lu teaches the treatment of disease with stem cell therapy, specifically administering mesenchymal stem cells (MSCs) for the treatment of the symptoms of diabetes (abstract, page 28). Regeneration and healing of damaged tissue is described (healing of ulcers in tissue)(page 33 section 3.5). Lu teaches wherein the disease is a result of peripheral artery disease (PAD) (page 26 Introduction). Lu teaches wherein the population of stem cells comprises multipotent cells, specifically mesenchymal stem cells (MSCs) (Title, abstract, pages 26-28).
Lu does not specifically include blebbistatin in the composition of MSCs administered.
Martin-Rendon teach methods of treating ischemic conditions, such as peripheral artery disease (PAD), by administering therapeutic cells. These therapeutic cells can be combined with supportive cells, such as mesenchymal stem cells (MSCs), for repair of damaged tissue in PAD (page 19 lines 1-14). The MSCs can be expanded on artificial tissue grafts or coating stents for administration to patients (page 19 lines 15-23).
Singh teach adhesive signature-based methods for the isolation of stem cells (title). Cells of interest include stem cell cultures intended for transplantation (page 11 lines 33-36). The substrate that the cells are adhered to can be coated with various substances such as fibronectin, collagen or blebbistatin (page 12 lines 12-18).
Schenk ‘819 teach a composition that contains mesenchymal stem cells and Blebbistatin (page 19 2nd paragraph) and suggest that this composition can be included as part of a pharmaceutical preparation (page 19 3rd paragraph). The Blebbistatin is taught to provide the benefit of greatly enhancing suspension survival of adherent cells such as MSCs (page 17, 4th paragraph). Blebbistatin can be used for coating the surface of a medical device such as a stent, patch or artificial blood vessel with cells that would otherwise have a low affinity to a surface (page 6), including attachment to microcarrier substrates (page 15). Schenk also describe how blebbistatin protects MSCs during stressful events such as freezing and thawing (page 5 last paragraph).
One of ordinary skill in the art would have been motivated to include blebbistatin in the method of Lu as part of the administered composition of stem cells because Martin-Rendon and Schenk teach that MSCs can be administered to patients via cell coated substrates such as stents, grafts or microcarriers and Singh teach that blebbistatin can be used to coat a substrate to provide for beneficial stem cell attachment. The combination of the stem cells and the blebbistatin prior to administration provides for an incubation period of time wherein the two ingredients interact (especially if the blebbistatin is used to coat a substrate that the MSCs are then attached to). One of ordinary skill in the art would have had a reasonable expectation of success because Schenk ‘819 indicates that a combination of mesenchymal stem cells and Blebbistatin are suitable for use in pharmaceutical preparations (page 19 last paragraph), and Lu and Martin-Rendon are administering mesenchymal stem cells as a pharmaceutical.
Regarding claim 18, Lu teaches wherein the disease is associated with an ankle brachial pressure index (ABI) of less than 0.7 (abstract, page 27 Table 1).
Regarding claim 19, Lu teaches wherein the disease has resulted in critical limb ischemia (Title, abstract, page 26 introduction).
Regarding claim 20, Lu teaches wherein the disease has resulted in skin ulceration (Title, abstract, page 26, page 27 Table 1). Gangrene may be present as well (page 26) and is not excluded from the reference study as long as it is dry and below the ankle (page 27, Table 1).
Therefore, the combined teachings of Lu et al, Martin-Rendon et al, Singh et al, and Schenk ‘819 render obvious Applicant's invention as claimed.
Claims 17-20 are rejected under pre-AlA 35 U.S.C. 103(a) as being unpatentable over Lu et al (Diabetes Research and Clinical Practice, 2011-from IDS filed 08/14/2024) in view of Chen et al (CN 102940631-published Feb 27, 2013,-from IDS filed 08/14/2024, plus full translation) and Schenk et al (WO 2012/062819-from IDS filed 08/14/2024).
Regarding claim 17, Lu teaches the treatment of disease with stem cell therapy, specifically administering mesenchymal stem cells (MSCs) for the treatment of the symptoms of diabetes (abstract, page 28). Regeneration and healing of damaged tissue is described (healing of ulcers in tissue)(page 33 section 3.5). Lu teaches wherein the disease is a result of peripheral artery disease (PAD) (page 26 Introduction). Lu teaches wherein the population of stem cells comprises multipotent cells, specifically mesenchymal stem cells (MSCs) (Title, abstract, pages 26-28).
Lu does not specifically include blebbistatin in the composition of MSCs administered.
Chen teaches methods that involve the medicinal application of blebbistatin in promoting stem cell survival (Title, page 1, claims 1-2). The stem cells include mesenchymal stem cells (page 1 claims 1-2). Blebbistatin is also taught as an active ingredient in a pharmaceutical composition for promoting stem cell survival (page 1 claim 2, page 5 para 10) and that it can be administered in combination with other medications for the prevention, management, treatment, or improvement of a condition or one or more symptoms thereof...for example recombinant cells capable of expressing SNX11 (page 4 para 7). Blebbistatin can be administered together with other biologically active agents and the administration can be systemic or local (page 4 para 8).
Schenk ‘819 teach a composition that contains mesenchymal stem cells and Blebbistatin (page 19 2nd paragraph) and suggest that this composition can be included as part of a pharmaceutical preparation (page 19 3rd paragraph). The Blebbistatin is taught to provide the benefit of greatly enhancing suspension survival of adherent cells such as MSCs (page 17, 4th paragraph). Blebbistatin can be used for coating the surface of a medical device such as a stent, patch or artificial blood vessel with cells that would otherwise have a low affinity to a surface (page 6), including attachment to microcarrier substrates (page 15). Schenk also describe how blebbistatin protects MSCs during stressful events such as freezing and thawing (page 5 last paragraph).
One of ordinary skill in the art would have been motivated to include blebbistatin in the method of Lu as part of the administered composition of stem cells because Chen teaches that blebbistatin is suitable as an active ingredient in a pharmaceutical composition and can promote stem cell survival and Lu is administering a therapeutic stem cell composition that would benefit from this effect. Enhancing the survival of stem cells allows for the continuation and thus enhancement of their effects and thus enhancement of regeneration of damaged tissue. The combination of the stem cells and the blebbistatin prior to administration provides for an incubation period of time wherein the two ingredients interact (especially if the blebbistatin is used to coat a substrate that the MSCs are then attached to). One of ordinary skill in the art would have had a reasonable expectation of success because Schenk ‘819 indicates that a combination of mesenchymal stem cells and Blebbistatin are suitable for use in pharmaceutical preparations and Lu is administering mesenchymal stem cells as a pharmaceutical.
Regarding claim 18, Lu teaches wherein the disease is associated with an ankle brachial pressure index (ABI) of less than 0.7 (abstract, page 27 Table 1).
Regarding claim 19, Lu teaches wherein the disease has resulted in critical limb ischemia (Title, abstract, page 26 introduction).
Regarding claim 20, Lu teaches wherein the disease has resulted in skin ulceration (Title, abstract, page 26, page 27 Table 1). Gangrene may be present as well (page 26) and is not excluded from the reference study as long as it is dry and below the ankle (page 27, Table 1).
Therefore, the combined teachings of Lu et al, Chen et al and Schenk ‘819 render obvious Applicant's invention as claimed.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
DeLucas et al., " Membrane Blebbing Is Required for Mesenchymal Precursor Migration", PLOS ONE, 2016, 11(3), pp. 1-16.
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