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 . 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 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.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7 Oct, 2025 has been entered.
Election/Restrictions
Applicants elected a treatment including SPARC, pluripotent stem cells or derivatives, SDF-1, to treat heart failure without traverse in the reply filed on 2 Aug, 2019 and the phone call with Jessica Lewis, applicant’s representative, on 21 Aug, 2019. In the response of 6 Jan, 2020, applicants have amended the claims so that they no longer read on applicant’s elected species.
Claims Status
Claims 14, 15, 17-22, and 31-41 are pending.
Claims 17, 21, 22, 35, and 37 have been withdrawn due to an election/restriction requirement.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
first rejection
Claims 14, 15, 18-20, 31-34, 36, 38, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Matheny et al (US 20070014773, previously cited) in view of Zeng et al (Int. Heart J (2013) 54 p40-44, cited by applicants) with evidentiary support from Iwazawa et al (US 20150202344, previously cited).
Matheny et al describe injectable extracellular matrix formulations for regenerating myocardium (abstract) after such disorders has heart failure (paragraph 2). The advantage of using an injectable formulation rather than a surgically applied patch is the avoidance of surgery, with the risk of infection, surgical challenges, and longer recovery time (paragraph 8). The actual extracellular matrix is not considered very important, with many different collagen based systems described as useable in the system (paragraph 43) although there is some teaching of using a matrix appropriate for the cell type used (paragraphs 25 and 68). The compositions may include cells and other components to optimize the regenerative process (abstract). Note that cells are listed as a component in a Markush group of compounds that can be added (paragraph 13), not compounds that must be added – the reference clearly regards cells as optional. Other peptides and proteins can be added to more closely mimic the native matrix (paragraph 72), as well as growth factors, such as PDGF, EGF, and TGF-β (paragraph 73). Grinding an extracellular matrix after freezing with liquid nitrogen is discussed (paragraph 85); as evidenced by Iwazawa et al, this can produce particles around 50-100 µm in size (example 2, paragraph 173). Lyophilized powders that are reconstituted before use are discussed (paragraph 82); presumably these would be ground to similar size as the frozen and ground materials. These materials can be direct injected, using a needle and a syringe (paragraph 86). The material can be made into an injectable liquid, gel, or emulsion (paragraph 61), which is read as adding a liquid carrier suitable for injection. Note that the first example is a prophetic example where an extracellular matrix was injected without cells (paragraph 94).
The difference between this reference and the instant claims is that this reference does not describe the same matrix.
Zeng et al discuss using extracellular matrix material produced by cardiac fibroblasts in vitro (title). The cells were grown to confluence after three passages, allowed to produce an extracellular matrix material for 7 days, then the cells removed (p41, 1st column, 3d paragraph). Note that this is almost the same method used by applicants to produce their extracellular matrix (note claim 31), so it would be expected by one of skill in the art to produce a very similar material (and meet the composition limitations of claims 14 and 38). The material was better than the standard collagen for the culture of ventricular cells; the cells had elevated cell function and metabolism (p43, 1st column, 4th paragraph). Note that, while the material contained collagen, this did not appear to be the major component (fig 1e, p41, 1st column, bottom of page). The material is proposed as an excellent scaffold for tissue engineering (p43, 2nd column, 2nd paragraph). While the reference does not explicitly discuss the limitations of the matrix thickness and the plating density, this is a source limitation. The courts have ruled that source limitations in a method of use claim are treated as product by process limitations (note Biogen v EMD Serono, 976 F.3d 1326, for example). The MPEP states that “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (MPEP 2113). This reference teaches the advantages of cardiac fibroblast derived extracellular matrix for cardiac tissue engineering.
Therefore, it would be obvious to use the material of Zeng et al in the injectable formulations of Matheny et al, as Zeng et al show that this material provides for improved activity of cardiac cells. As Matheny et al describe using varied extracellular matrix materials, an artisan in this field would attempt this modification with a reasonable expectation of success.
Matheny et al teach cell free injection of lyophilized extracellular matrix proteins for treatment of heart failure. Note that the grinding of the material after lyophilization meets the limitations of “fragments,” and the particle size (from Iwasawa et al) is much less than the diameter of the bore of an 18 gauge needle (paragraph 21), and can reasonably flow through it in a formulation. Matheny et al discuss reconstitution, which meets the limitation of an injectable carrier, and discusses injectable liquids, gels, and emulsions, all of which are suspensions (defined (Merriam Webster online) as “a substance when its particles are mixed with but undissolved in a solid or fluid”)). Zeng et al teach a matrix that meets the protein limitations. Note that the matrix of Zeng comes from cultured cells that are more than just a monolayer (note fig 1a). Alternatively, the difference between a 3 dimensional matrix and a non-3 dimensional matrix is the plating density. However, this is merely a difference in concentration, which is not a patentable distinction (MPEP 2144.05(II)(A)). Alternatively, as there is no evidence that the limitation of “3 dimensional” in the ECM matrix makes a difference in the material of the matrix, violating this limitation generates an equivalent material. Thus, the combination of references render obvious claims 14, 15, and 38.
Matheny et al teach the addition of growth factors, including many that overlap with the Markush group of claim 20, rendering claims 18-20 obvious.
Zheng et al discuss isolating cardiac fibroblasts, expanding for 3 passages, growing to confluence for 7 days, and decellularizing the composition – note that applicants let theirs grow for the same amount of time (7-15 days, paragraph 87). Matheny et al teach lyophilization. While the reference does not teach the cell density at plating, the authors of the reference must have plated at an appropriate density. Alternatively, differences in cell plating density are compensated for by differences in cell growth time to confluence, i.e. are equivalent. Thus, the combination of references render obvious claims 31 and 32.
Zhang et al leave their cells at confluence for the same length of time as applicants, so will necessarily have the same thickness of deposited matrix, rendering obvious claims 33 and 34.
Zhang et al does not discuss removal of the extracellular matrix, so it must have been attached to the culture surface during decellularization, rendering obvious claim 36.
response to applicant’s arguments:
Applicants argue that the calculation based on the data of Murad et al does not included non-structural proteins, that Zeng et al shows an extensive collagen network, and claim that Zeng et al does not discuss the critical cell density.
Applicant's arguments filed 7 Oct, 2025 have been fully considered but they are not persuasive.
Applicants argue that the calculations based on the data of Murad et al does not include non-structural proteins. However, for non-structural proteins to push the concentration to outside the claim limitations, they would have to be around ¾ of the total. Zeng et al teaches that the material they make is an extracellular matrix (title), which would lead a person of skill in the art to believe non-structural proteins are a minimal amount of the material. It should also be noted that applicants argument that Murad et al includes non-structural proteins means that the whole argument is not based on an apples to apples comparison.
Applicants argue that Zeng et al shows extensive collagen networks. Fig 1e shows some collagen in the material:
PNG
media_image1.png
233
230
media_image1.png
Greyscale
, but it is clear that it is not a large percentage of the total material. If this was more than 50% of the total, as applicants argue, the stain would cover at least 50% of the image. It clearly is a much smaller percentage than that. Extensive collagen network is not the same as large amount of collagen.
Applicants argue that the critical plating density was not reached. Applicants have provided zero evidence that the plating density is critical – it is known in the art that cardiac fibroblasts plated on a surface will form a monolayer, then stop growing (Agocha et al, previously cited, p90, 1st column, 4th paragraph). While it is not clear if Zeng et al used a plating density similar to that of applicants, a person of skill in the art would reasonably believe that the material of Zeng et al is the same as what applicants are claiming.
second rejection
Claims 14, 15, 18-20, 31-34, 36, and 38-41 are rejected under 35 U.S.C. 103 as being unpatentable over Matheny et al (US 20070014773, previously cited) in view of Zeng et al (Int. Heart J (2013) 54 p40-44, cited by applicants) and Iyer et al (Development (April 2015) 142(8) p1528-1541) with evidentiary support from Iwazawa et al (US 20150202344, previously cited).
The teachings of Matheny et al and Zeng et al were given above, and will not be repeated here. Please note that these references render obvious claims 14, 15, 18-20, 31-34, 36, and 38.
The difference between these references and the remaining claim is that these references do not discuss using cardiac fibroblasts derived from induced pluripotent stem cells.
Iyer et al discusses differentiation of cardiac cells from pluripotent stem cell (abstract), including cardiac fibroblasts (abstract). These stem cells can be human induced pluripotent stem cells (p1538, 2nd column, 4th paragraph). This reference mentions generating cardiac fibroblasts from induced pluripotent stem cells.
Therefore, it would be obvious to use the cardiac fibroblasts of Iyer et al for the cardiac fibroblasts of Zeng et al, as a simple substitution of one known element (the cells of Zeng et al) for another (the cells of Iyer et al) yielding expected results (cardiac fibroblasts that can produce matrix). As these are the same cells, an artisan in this field would attempt this substitution with a reasonable expectation of success.
response to applicant’s arguments:
Applicants have repeated the same arguments as used for the previous rejection under this statute, which were discussed above.
third rejection
Claims 14, 15, 18-20, 31-34, 36, and 38-41 are rejected under 35 U.S.C. 103 as being unpatentable over Matheny et al (US 20070014773, previously cited) in view of Schmuck et al (Cardiovasc. Eng. Technol. (March 2014) 5(1) p119-131, previously cited) and Iyer et al (Development (April 2015) 142(8) p1528-1541) with evidentiary support from Iwazawa et al (US 20150202344, previously cited).
Matheny et al describe injectable extracellular matrix formulations for regenerating myocardium (abstract) after such disorders has heart failure (paragraph 2). The advantage of using an injectable formulation rather than a surgically applied patch is the avoidance of surgery, with the risk of infection, surgical challenges, and longer recovery time (paragraph 8). The actual extracellular matrix is not considered very important, with many different collagen based systems described as useable in the system (paragraph 43) although there is some teaching of using a matrix appropriate for the cell type used (paragraphs 25 and 68). The compositions may include cells and other components to optimize the regenerative process (abstract). Note that cells are listed as a component in a Markush group of compounds that can be added (paragraph 13), not compounds that must be added – the reference clearly regards cells as optional. Other peptides and proteins can be added to more closely mimic the native matrix (paragraph 72), as well as growth factors, such as PDGF, EGF, and TGF-β (paragraph 73). Grinding an extracellular matrix after freezing with liquid nitrogen is discussed (paragraph 85); as evidenced by Iwazawa et al, this can produce particles around 50-100 µm in size (example 2, paragraph 173). Lyophilized powders that are reconstituted before use are discussed (paragraph 82); presumably these would be ground to similar size as the frozen and ground materials. These materials can be direct injected, using a needle and a syringe (paragraph 86). The material can be made into an injectable liquid, gel, or emulsion (paragraph 61), which is read as adding a liquid carrier suitable for injection. Note that the first example is a prophetic example where an extracellular matrix was injected without cells (paragraph 94).
The difference between this reference and the instant claims is that this reference does not describe the same matrix.
Schmuck et al discuss using cardiac fibroblast ECM to generate scaffolds for heart care (abstract). Cells were isolated from rats then plated at a density of 1.1-2.2x105 cells per cm2 after three passages (2nd page, 3d and 4th paragraphs). These were incubated for 10-14 days, removed from the culture dish with EDTA, and decellularized (p2, 4th paragraph, continues to p5, 1st paragraph). The thickness of the scaffolds were between 50 to 150 µm (p5, 4th paragraph), which meets applicant’s definition of a 3 dimensional matrix. The material was 82.1% fibronectin, with the remainder being collagen type I, IAI, IA2, III, II, XI, and elastin (p5, 5th paragraph, continues to p6). The material was seeded with cells and used in a model of myocardial infarction (4th page, 4th paragraph). The material did not require sutures or glue, does not cause acute toxicity, and has a composition homologous to the recipient myocardium (6th page, 6th paragraph). This reference discusses a matrix used for a similar purpose as that of Matheny et al.
Iyer et al discusses differentiation of cardiac cells from pluripotent stem cell (abstract), including cardiac fibroblasts (abstract). These stem cells can be human induced pluripotent stem cells (p1538, 2nd column, 4th paragraph). This reference mentions generating cardiac fibroblasts from induced pluripotent stem cells.
Therefore, it would be obvious to use the material of Schmuck et al in the injectable formulations of Matheny et al, as Schmuck et al show that this material is useful for a similar purpose, and is homologous to the recipient myocardium and has no acute toxicity. As Matheny et al describe using varied extracellular matrix materials, an artisan in this field would attempt this modification with a reasonable expectation of success.
Furthermore, it would be obvious to use the cardiac fibroblasts of Iyer et al for the cardiac fibroblasts of Schmuck et al, as a simple substitution of one known element (the cells of Schmuck et al) for another (the cells of Iyer et al) yielding expected results (cardiac fibroblasts that can produce matrix). As these are the same cells, an artisan in this field would attempt this substitution with a reasonable expectation of success.
Matheny et al teach cell free injection of lyophilized extracellular matrix proteins for treatment of heart failure. Note that the grinding of the material after lyophilization meets the limitations of “fragments,” and the particle size (from Iwasawa et al) is much less than the diameter of the bore of an 18 gauge needle (paragraph 21), and can reasonably flow through it in a formulation. Matheny et al discuss reconstitution, which meets the limitation of an injectable carrier, and discusses injectable liquids, gels, and emulsions, all of which are suspensions (defined (Merriam Webster online) as “a substance when its particles are mixed with but undissolved in a solid or fluid”). Schmuck et al teach a matrix that meets the protein limitations. Thus, the combination of references renders obvious claims 14, 15, 38, and 41.
Matheny et al teach the addition of growth factors, including many that overlap with the Markush group of claim 20, rendering claims 18-20 obvious.
Schmuck et al discuss isolating cardiac fibroblasts, expanding for 3 passages, plating at between 100,000-500,000 cells/cm2, and decellularizing the composition. Matheny et al teach lyophilization. Thus, the combination of references renders obvious claims 31 and 32.
Zhang et al leave their cells at confluence for the same length of time as applicants, so will necessarily have the same thickness of deposited matrix, rendering obvious claims 33 and 34.
Zhang et al does not discuss removal of the extracellular matrix, so it must have been attached to the culture surface during decellularization, rendering obvious claim 36.
Iyer et al discusses production of cardiac fibroblast cells from pluripotent stem cells, rendering obvious claims 39 and 40.
response to applicant’s arguments
Applicants argue that the purpose of the material of Schmuck is different than that of the claims, that Matheny et al does not lead a skilled person to believe that the material can be injected into the heart, and that the cell derived material was believed to be inferior.
Applicant's arguments filed 7 Oct, 2025 have been fully considered but they are not persuasive.
Applicants argue that the purpose of the material of Schmuck is different than that of the claims. It is not clear how this overcomes the rejection. This is not a teaching away, and does not suggest that the material will not work.
Applicants argue that a person of skill in the art would believe the material of Schmuck et al would be inferior to some other material and unsuitable. Applicants point to a number of references which they say suggests that the material of Schmuck et al would have inferior tensile properties. However, the material in the applications of Matheney et al is ground small enough to be injected. Tensile strength is not the primary concern, as there is no patch consisting of a single piece of material. Note that some of the references that applicants point to do not appear to teach what applicants are arguing. Note that Chen et al, for example, does not suggest that extracellular matricies are inferior, but rather, discuss issues with scaleup, which have nothing to do with the claim limitations.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
first rejection
Claims 14, 15, 18-20, 31-34, 36, 38, and 41 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 11 of copending Application No. 16/056,033 (US 20180353646) in view of Matheny et al (US 20070014773, cited by applicants) with evidentiary support from Iwazawa et al (US 20150202344).
Competing claim 1 describes a method for preparing a 3D cardiac extracellular matrix, while claim 11 describes the number of passages. Note that these methods are very similar to that described by applicants for making their extracellular matrix, and would thus be expected to have a similar composition. Together, these give the identical method of instant claim 31, save the lyophilization. Note that the utility of the material is for treating a subject with a cardiac disease, such as heart failure (paragraph 51).
The difference between the competing claims and the instant claims is that the competing claims do not describe how to use the material.
Matheny et al describe injectable extracellular matrix formulations for regenerating myocardium (abstract). The advantage of using an injectable formulation rather than a surgically applied patch is the avoidance of surgery, with the risk of infection, surgical challenges, and longer recovery time (paragraph 8). The actual extracellular matrix is not considered very important, with many different collagen based systems described as useable in the system (paragraph 43) although there is some teaching of using a matrix appropriate for the cell type used (paragraphs 25 and 68). Cells can be added to the matrix, with pluripotent cells specifically mentioned (paragraph 69). Other peptides and proteins can be added to more closely mimic the native matrix (paragraph 72), as well as growth factors, such as PDGF, EGF, and TGF-β (paragraph 73). Grinding an extracellular matrix after freezing with liquid nitrogen is discussed (paragraph 85); as evidenced by Iwazawa et al, this can produce particles around 50-100 µm in size (example 2, paragraph 173). Lyophilized materials that are reconstituted before use are discussed (paragraph 82). These materials can be direct injected, using a needle and a syringe (paragraph 86). The material can be made into an injectable liquid, gel, or emulsion (paragraph 61), which is read as adding a liquid carrier suitable for injection. This reference teaches that injectable formulations with components similar to those of the competing claims are used for similar purposes.
Therefore, it would be obvious to use the material of the competing claims in the method of Matheny et al, as a simple substitution of one known element for another yielding expected results. As Matheny et al describe similar compositions, an artisan in this field would attempt this process with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments:
Applicants state that they will respond to this rejection when all other grounds of rejection have been overcome. However, until the rejection is otherwise overcome, it will remain valid.
second rejection
Claims 14, 15, 18-20, 31-34, 36, 38, and 41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of U.S. Patent No. 9,744,265 in view of Matheny et al (US 20070014773, cited by applicants) with evidentiary support from Iwazawa et al (US 20150202344).
Competing claim 1 describes a method for preparing a 3D cardiac extracellular matrix, that is almost identical with that of instant claim 31 while claim 3 gives the same matrix thicknesses as instant claim 34. Note that competing claim 1 explicitly states that the protein composition is the same as required for the instant claims. Note that the utility of the material is for treating a subject with a cardiac disease, such as heart failure (column 8, line 61).
The difference between the competing claims and the instant claims is that the competing claims do not describe how to use the material.
Matheny et al describe injectable extracellular matrix formulations for regenerating myocardium (abstract). The advantage of using an injectable formulation rather than a surgically applied patch is the avoidance of surgery, with the risk of infection, surgical challenges, and longer recovery time (paragraph 8). The actual extracellular matrix is not considered very important, with many different collagen based systems described as useable in the system (paragraph 43) although there is some teaching of using a matrix appropriate for the cell type used (paragraphs 25 and 68). Cells can be added to the matrix, with pluripotent cells specifically mentioned (paragraph 69). Other peptides and proteins can be added to more closely mimic the native matrix (paragraph 72), as well as growth factors, such as PDGF, EGF, and TGF-β (paragraph 73). Grinding an extracellular matrix after freezing with liquid nitrogen is discussed (paragraph 85); as evidenced by Iwazawa et al, this can produce particles around 50-100 µm in size (example 2, paragraph 173). Lyophilized materials that are reconstituted before use are discussed (paragraph 82). These materials can be direct injected, using a needle and a syringe (paragraph 86). The material can be made into an injectable liquid, gel, or emulsion (paragraph 61), which is read as adding a liquid carrier suitable for injection. This reference teaches that injectable formulations with components similar to those of the competing claims are used for similar purposes.
Therefore, it would be obvious to use the material of the competing claims in the method of Matheny et al, as a simple substitution of one known element for another yielding expected results. As Matheny et al describe similar compositions, an artisan in this field would attempt this process with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments:
Applicants state that they will respond to this rejection when all other grounds of rejection have been overcome. However, until the rejection is otherwise overcome, it will remain valid.
third rejection
Claims 14, 15, 18-20, 31-34, 36, and 38-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, and 8 U.S. Patent Number 12,419,993 in view of Matheny et al (US 20070014773, previously cited) and Iyer et al (Development (April 2015) 142(8) p1528-1541) with evidentiary support from Iwazawa et al (US 20150202344, previously cited).
Competing claim 1 discusses a method of preparing a cardiac extracellular matrix, comprising plating fibroblasts at a cell density between 100,000 and 500,000 cells per cm2, while claims 4 and 5 describe removing the matrix from the surface it was grown on and decellularizing the matrix respectively. Competing claim 10 discusses adding bioactive proteins that are therapeutic for cardiac disease or injury, incidentally giving an intended use to the invention.
The difference between the competing claims and the instant claims is that the competing claims do not describe using the matrix.
Matheny et al describe injectable extracellular matrix formulations for regenerating myocardium (abstract) after such disorders has heart failure (paragraph 2). The advantage of using an injectable formulation rather than a surgically applied patch is the avoidance of surgery, with the risk of infection, surgical challenges, and longer recovery time (paragraph 8). The actual extracellular matrix is not considered very important, with many different collagen based systems described as useable in the system (paragraph 43) although there is some teaching of using a matrix appropriate for the cell type used (paragraphs 25 and 68). The compositions may include cells and other components to optimize the regenerative process (abstract). Note that cells are listed as a component in a Markush group of compounds that can be added (paragraph 13), not compounds that must be added – the reference clearly regards cells as optional. Other peptides and proteins can be added to more closely mimic the native matrix (paragraph 72), as well as growth factors, such as PDGF, EGF, and TGF-β (paragraph 73). Grinding an extracellular matrix after freezing with liquid nitrogen is discussed (paragraph 85); as evidenced by Iwazawa et al, this can produce particles around 50-100 µm in size (example 2, paragraph 173). Lyophilized powders that are reconstituted before use are discussed (paragraph 82); presumably these would be ground to similar size as the frozen and ground materials. These materials can be direct injected, using a needle and a syringe (paragraph 86). The material can be made into an injectable liquid, gel, or emulsion (paragraph 61), which is read as adding a liquid carrier suitable for injection. Note that the first example is a prophetic example where an extracellular matrix was injected without cells (paragraph 94). This reference discusses using a matrix to treat a cardiac injury.
Iyer et al discusses differentiation of cardiac cells from pluripotent stem cell (abstract), including cardiac fibroblasts (abstract). These stem cells can be human induced pluripotent stem cells (p1538, 2nd column, 4th paragraph). This reference mentions generating cardiac fibroblasts from induced pluripotent stem cells.
Therefore, it would be obvious to use the material of the competing claims to treat the disorders of Matheny et al, as that reference uses similar materials for that purpose. As Matheny et al is very general as to the material used, an artisan in this field would attempt this method with a reasonable expectation of success.
Furthermore, it would be obvious to use the method of Iyer et al to produce the cardiac fibroblasts used in the competing claims, as a simple substitution of one known element (the production method of Iyer et al) for another (the undescribed production method of the competing claims) yielding expected results (an extracellular matrix).
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants state that they will respond to this rejection when all other grounds of rejection have been overcome. However, until the rejection is otherwise overcome, it will remain valid.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
Examiner interviews are available via telephone and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658