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 .
1. Claims 1, 3, 5 – 6, 8, 10 – 21, and 23 – 32 are pending. Claims 6, 8, and 10 – 12 are under consideration.
Claim Interpretation
2. For the purpose of applying prior art, “formulated for intravascular infusion” in claim 6 is interpreted as the soluble ECM composition is in liquid form based on Applicant’s specification at para. 0085 and para. 0088.
3. For the purpose of applying prior art, “free-flowing” of claim 6 is given the broadest reasonable interpretation to include any liquid of any viscosity.
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.
4. Claim(s) 6, 8, 11, and 12 remain rejected under 35 U.S.C. 103 as being unpatentable over Woo (KR-101628821-B1; Filed 03/02/2015, Published 06/13/2016; previously cited), hereinafter Woo, in view of Johnson (Johnson, Todd D., et. al. Nanotechnology 22.49 (2011): 494015; previously cited), hereinafter Johnson in view of Efraim (Efraim, Yael, et al. Acta biomaterialia 50 (2017): 220-233; previously cited), hereinafter Efraim. A machine translation of KR-101628821-B1 is provided. The translation was performed on 02/19/2026 of pages 4 – 15 of the original document.
Regarding claim 6, Woo teaches a soluble ECM composition (SSE) diluted to an appropriate concentration with 1xPBS (“formulated for intravascular infusion” and “free-flowing liquid”) comprising decellularized, digested, and neutralized tissue having at least a portion of solid ECM materials removed by centrifugation (page 39 – 40, para. 0066). Woo teaches the soluble ECM was filtered through a 0.2 µm (200 nm) syringe filter (“wherein the soluble ECM composition passes through a 250 nm size exclusion filter” and “free-flowing liquid”) (page 40, para. 0066). Woo teaches the soluble ECM composition is a transparent liquid at room temperature (“free-flowing liquid”) (page 40, para. 0066; Figure 2H; page 30, para. 0056). Woo does not teach “wherein the soluble ECM composition comprises soluble matrix particles having an average diameter of less than 100 nm” or “wherein the soluble ECM composition binds to damaged blood vessels following infusion or injection in vivo”.
Regarding claims 11 and 12, Woo teaches the soluble ECM is derived from animal tissue (claim 11) that is liver (claim 12) (page 34 – 35, para. 0059 – 0060; page 61 – 62, para. 0091 - 0092).
Woo does not teach “wherein the soluble ECM composition comprises soluble matrix particles having an average diameter of less than 100 nm” or “wherein the soluble ECM composition binds to damaged blood vessels following infusion or injection in vivo” of claim 6 or the soluble ECM composition forms a gel in tissue following infusion or injection in vivo of claim 8. However, Woo teaches the soluble ECM retained glycosaminoglycans (GAGs), collagen, elastin, and proteins after filtration through a 0.2 µm filter (page 63 – 66, para. 0094; Figure 3; page 30, para. 0056). Woo teaches embryonic stem cells could be cultured on the soluble ECM (page 66 – 69). Woo teaches obtaining and utilizing natural ECM from specific tissues may provide an ideal growth environment, as it can more closely mimic the cell-specific in vivo microenvironment (page 5, para. 0004). Woo teaches the preparation of the solubilized ECM was performed under sterile conditions and the sterilization efficiency indicated no bacterial contamination was observed (page 40, para. 0066; page 60, para. 0090). Woo teaches current research in tissue engineering and regenerative medicine focuses on scaffold materials that are biocompatible and embody the structure, morphology, chemical signals, and biological cues of the natural environment and ECM is an ideal candidate for tissue engineering because ECM directs important morphological organization and physiological functions (page 5 – 6, para. 0004; page 75, para. 0102).
Regarding “wherein the soluble ECM composition comprises soluble matrix particles having an average diameter of less than 100 nm” of claim 6, Johnson teaches a soluble ECM (myocardial matrix) composition comprising decellularized, digested, and neutralized porcine heart having a portion of solid ECM materials removed that comprises soluble ECM particles having an average diameter of less than 100 nm (page 2, left col. last para. and right col. para. 1 – 2; Figure 4; page 4, left col. para. 3; page 8, left col. para. 3). Johnson teaches the main component of the myocardial matrix is collagen but it has been shown to contain other ECM components including sulfated GAGs (Abstract; page 9, left col. para. 2).
Regarding the soluble ECM composition forms a gel in tissue following infusion or injection in vivo of claim 8, Johnson teaches upon injection and increase in temperature, the decellularized ECMs self-assemble into porous gels (Abstract; Figure 1; page 3, right col. para. 2; page 7, right col. para. 2; page 8, left col. para. 2).
Johnson does not teach “wherein the soluble ECM composition binds to damaged blood vessels following infusion or injection in vivo” of claim 6. However, Johnson teaches the field of tissue engineering aims to create and tailor the extracellular environment by creating custom scaffolds and one method is to utilize or mimic the native environment including tissue specific biochemical composition and structure (page 1, right col. para. 1). Johnson teaches each tissue in the body contains a unique ECM, so decellularized materials have distinctive compositions specific to their tissue of origin and such diversity allows for the development of tissue specific scaffolds for appropriate cell-matrix interactions (page 2, left col. para. 2). One would have been motivated to combine the teachings of Woo and Johnson because both teach tissue-specific solubilized ECM compositions for tissue engineering comprising decellularized, digested, and neutralized tissue having at least a portion of solid ECM material removed.
Regarding “wherein the soluble ECM composition binds to damaged blood vessels following infusion or injection in vivo” of claim 6, Efraim teaches a solubilized ECM composition (pcECM) comprising decellularized, digested, and neutralized porcine heart that binds to damaged hearts due to myocardial infarction (page 221, right col. para. 2 – 3; page 223, right col. para. 3; page 231, left col. para. 2). Efraim teaches injection of the pcECM to the infarcted area and improvements in cardiac dimensions and function were observed (page 222, right col. last para.; page 223, left col. para. 1; page 226, left col. para. 1 and right col. para. 2; Figure 4 and 5; page 230, left col. para. 2 and right col.). Efraim teaches in Figure 1D that the pcECM is transparent and can be successfully injected through a catheter where it gels at 37 °C (page 223, right col. para. 3). Efraim teaches the pcECM is composed of collagens and GAGs (page 223, right col. para. 3). Efraim teaches though ECM components in different tissues may be similar, each tissue holds a unique combination and 3D structure of macromolecules that provide the cells with the required cues and mechanical support (page 227, right col. para. 3). Efraim teaches cardiac acellular ECM should, therefore, be an ideal candidate biomaterial to serve as a scaffold for myocardial tissue engineering (page 227, right col. para. 3). Efraim teaches collagens and GAGs are known to not only be crucial for cell-ECM interactions but also for the gelling process (page 227, right col. para. 4). Efraim teaches the motivation behind the design of injectable solubilized ECM for cardiac therapy is to avoid invasive surgery and to facilitate cell delivery when applicable (page 221, left col. para. 3). Efraim teaches the pcECM gels not only preserved heart functions but also alleviated myocardial infarction damage and thus these gels are prospective scaffolds for the treatment of end-stage heart failure (page 231, right col. para. 2).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Woo regarding a sterile solubilized ECM composition that can pass through a 200 nm filter and retain ECM components including collagen and GAGs with the teachings of Johnson regarding a solubilized ECM composition comprising ECM components including collagen and GAGs with fiber diameters averaging less than 100 nm with the teachings of Efraim regarding a solubilized ECM composition comprising collagens and GAGs that improved cardiac dimensions and function following myocardial infarction to arrive at the claimed soluble extracellular matrix (ECM) ECM composition formulated for intravascular infusion comprising decellularized, digested and neutralized tissue having at least a portion of solid ECM materials removed therefrom, wherein the soluble ECM composition passes through a 250 nm size exclusion filter, wherein the soluble ECM composition comprises soluble matrix particles having an average diameter of less than 100 nm, wherein the soluble ECM composition is a transparent liquid at room temperature and wherein the soluble ECM composition binds to damaged blood vessels following infusion or injection in vivo. One would have been motivated to combine the teachings of Woo, Johnson, and Efraim in a sterile soluble ECM composition for tissue engineering and regenerative medicine that minimizes invasive surgery as Woo teaches current research in tissue engineering and regenerative medicine focuses on scaffold materials that are biocompatible and embody the structure, morphology, chemical signals, and biological cues of the natural environment and ECM is an ideal candidate for tissue engineering and Johnson teaches one method in tissue engineering is to utilize or mimic the native environment including tissue specific biochemical composition and structure and each tissue in the body contains a unique ECM, and Johnson teaches decellularized materials have distinctive compositions specific to their tissue of origin and such diversity allows for the development of tissue specific scaffolds and Efraim teaches the motivation behind the design of injectable solubilized ECM for cardiac therapy is to avoid invasive surgery and to facilitate cell delivery when applicable. One would have a reasonable expectation of success in combining the teachings as Woo, Johnson, and Efraim each teach the solubilized ECM comprises decellularized, digested, and neutralized tissue comprising collagens and GAG and Efraim teaches the pcECM gels not only preserved heart functions but also alleviated myocardial infarction damage.
5. Claim(s) 10 remains rejected under 35 U.S.C. 103 as being unpatentable over Woo (KR-101628821-B1; Filed 03/02/2015, Published 06/13/2016; previously cited), hereinafter Woo, in view of Johnson (Johnson, Todd D., et. al. Nanotechnology 22.49 (2011): 494015; previously cited), hereinafter Johnson in view of Efraim (Efraim, Yael, et al. Acta biomaterialia 50 (2017): 220-233; previously cited), hereinafter Efraim as applied to claims 6, 8, 11, and 12 above, and further in view of Seif (Seif-Naraghi, et. al. Science translational medicine 5.173 (2013): 173ra25-173ra25; previously cited), hereinafter Seif which is cited on the IDS filed 01/10/2023.
Woo in view of Johnson and Efraim make obvious the limitations of claim 6 as set forth above. Woo and Efraim teach seeded stem cells can adhere, survive, and proliferate in the solubilized ECM (page 74, para. 0101 of Woo; page 229, right col. para. 2 of Efraim). Efraim teaches the gels in vivo recruited smooth muscle cells suggesting vascularization of the transplanted scaffold (page 231, left col. para. 2). Woo, Johnson, and Efraim do not teach the composition fills the pores between endothelial cells following infusion or injection in vivo.
Seif teaches a solubilized ECM from porcine heart fills the pores between endothelial cells following injection into pigs after myocardial infarction (page 2, left col. para. 2 and right col. last para.; page 3, left col. para. 1; Figure 3). Seif teaches the solubilized ECM contributes to improvements in contractility by increasing a layer of muscle at the endocardium (page 5, right col. para. 1). Seif teaches it is known that there are more cardiac progenitor cells in failing hearts and thus by mitigating the harsh infarct milieu, the injected matrix may also provide a more appropriate environment as well as a physical scaffold for circulating stem cells to encourage repair and regeneration (page 5, right col. para. 1). Seif teaches a growing number of patients survive heart attacks but many develop heart failure and thus there is a pressing clinical need for new therapies to prevent progression of the negative left ventricular (LV) remodeling that follows myocardial infarction and leads to heart failure (page 1, left col. para. 1). Seif teaches the only successful treatments for end-stage heart failure are total heart transplantation and LV assist devices and both require invasive, inherently risky surgical procedures (page 1, left col. para. 1). Seif teaches given the tissue specificity of the ECM, it follows that the most appropriate scaffold to replace the damaged ECM after a myocardial infarction would be derived from myocardial tissue (page 1, right col. para. 2).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Woo regarding a sterile solubilized ECM composition that can pass through a 200 nm filter and retain ECM components including collagen and GAGs with the teachings of Johnson regarding a solubilized ECM composition comprising ECM components including collagen and GAGs with fiber diameters averaging less than 100 nm with the teachings of Efraim regarding a solubilized ECM composition comprising collagens and GAGs that improved cardiac dimensions and function following myocardial infarction with the teachings of Seif regarding a solubilized ECM composition that improves heart function following myocardial infarction to arrive at the claimed soluble extracellular matrix (ECM) ECM composition wherein the composition fills the pores between endothelial cells following infusion or injection in vivo. One would have been motivated to combine the teachings of Woo, Johnson, Efraim, and Seif in a sterile soluble ECM composition for cardiac regenerative medicine as Seif teaches a growing number of patients survive heart attacks but many develop heart failure and thus there is a pressing clinical need for new therapies to prevent heart failure and Seif teaches given the tissue specificity of the ECM, it follows that the most appropriate scaffold to replace the damaged ECM after a myocardial infarction would be derived from myocardial tissue. One would have a reasonable expectation of success in combining the teachings as Efraim and Seif each teach the solubilized ECM from porcine heart that preserved heart functions and also alleviated myocardial infarction damage.
Applicant Arguments/ Response to Arguments
6. Applicant Argues: Applicant asserts that the ECM of Woo is a viscous solution and not a solution which is free-flowing with similar viscosity to water that is transparent that comprises soluble matrix particles of less than 100 nm. Applicant asserts that Efraim and Seif do not teach or suggest a soluble ECM composition which is a transparent, non-gel liquid.
Response to Arguments: This is not found persuasive because the claim nor specification define “free-flowing” to mean a viscosity similar to water. Therefore, in giving “free-flowing” its broadest reasonable interpretation, Woo’s soluble ECM composition (SSE) diluted to an appropriate concentration with 1xPBS that is a transparent liquid at room temperature that retained glycosaminoglycans (GAGs), collagen, elastin, and proteins after filtration through a 0.2 µm filter reads on “free-flowing liquid at room temperature of amended claim 6.
Applicant Argues: Applicant asserts that Johnson does not disclose an ECM composition with an average particle size below 100 nm. Applicant asserts that soluble ECM materials only form a network of fibers when injected into solid tissue and in the case of Johnson the fibers comprising the gels have an average diameter of approximately 100 nm as shown in Figure 4. Applicant asserts that this does not indicate anything regarding the average diameter of the soluble ECM particles and the size of the particles of the composition of Johnson is directly compared to the claimed soluble ECM particles in Figure 14. Applicant asserts that Figure 14 shows that the Full MM material of Johnson has an average particle size significantly larger than 100 nm. Applicant asserts that Efraim and Seif do not teach or suggest a soluble ECM composition having an average particle size of less than 100 nm.
Response to Arguments: This is not found persuasive because Woo’s soluble ECM composition diluted to an appropriate concentration with 1xPBS as taught would have soluble matrix particles having an average diameter of less than 100 nm because Woo teaches the soluble ECM retained glycosaminoglycans (GAGs), collagen, elastin, and proteins after filtration through a 0.2 µm filter. Applicant’s specification at para. 0085 states that the difference between MM and SolMM is that SolMM is the supernatant that is passed through a 0.22 µm filter. Therefore, Applicant’s arguments and specification teach that the soluble ECM composition comprises soluble matrix particles with an average diameter of 100 nm as a result of the composition passing through a 250 nm size exclusion filter, and such a composition is taught by Woo. Further, as Johnson teaches that the average diameter in 1xPBS was less than 100 nm, the soluble ECM composition of Woo diluted in 1xPBS would have soluble matrix particles having an average diameter of less than 100 nm. Additionally, one of ordinary skill in the art would recognize that the formation of a network of fibers having an average diameter of 100 nm means that the monomers forming the network would have an average diameter of less than 100 nm.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. 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 ZANNA M BEHARRY whose telephone number is (571)270-0411. The examiner can normally be reached Monday - Friday 8:45 am - 5:45 pm.
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/Z.M.B./Examiner, Art Unit 1632
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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