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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-8) in the reply filed on 11/25/2025 is acknowledged.
Claims 1-12 are currently pending.
Claims 9-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 11/25/2025.
Claims 1-8 have been examined on their merits.
Claim Interpretation
Claims 1-8 are drawn to a method of preparing a tissue gel for transplantation. The phrase “for transplantation” is with regard to the final product produced by the method and is interpreted as requiring that the final product be in form suitable for such intended use. Baring evidence to the contrary, any method that includes the claimed method steps and structural elements is deemed to be meet this intended use provided that there is nothing in the final product produced that would render it unsuitable for transplantation.
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.
Claim(s) 1-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Seo et al (ACS Biomaterials Science and Engineering, published December 4, 2019).
Although the Seo reference cited above lists an inventor as one of the six authors of the reference, it is still applicable as prior art under 35 U.S.C. 102(a)(1).
Applicant may rely on the exception under 35 U.S.C. 102(b)(1)(A) to overcome this rejection under 35 U.S.C. 102(a)(1) by a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application, and is therefore not prior art under 35 U.S.C. 102(a)(1). Alternatively, applicant may rely on the exception under 35 U.S.C. 102(b)(1)(B) by providing evidence of a prior public disclosure via an affidavit or declaration under 37 CFR 1.130(b).
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Regarding claims 1-2, Seo discloses: a method for manufacturing a 3D culture scaffold, the method comprising the steps of: preparing a brain-derived decellularized extracellular matrix solution; applying a tensile force by using a tensioning device so that a polydimethylsiloxane (PDMS) chip is stretched; and loading the decellularized extracellular matrix solution on the stretched PDMS chip, followed by gelation, and restoring the PMDS chip to its original position, thereby manufacturing a 3D scaffold in which microfibers are isotropically aligned in a decellularized extracellular matrix; and a 3D scaffold in which microfibers are isotropically aligned in a decellularized extracellular matrix, the 3D scaffold being manufactured by the method (see: abstract, page 611, left column, line 34- page 611, right column, line 16; page 612, right column, lines 48-57; page 617, left column, line 2-page 618, left column, line 11; and figure 5а).
While Seo does not specifically state that the final 3D scaffold product is intended for transplantation, they do teach that the feature wherein a manufactured 3D culture scaffold provides an optimal microenvironment for the differentiation and growth of neurites by providing brain tissue-mimicking properties; and the feature wherein active components present in the extracellular matrix of the brain are preserved, thus having the advantage of providing a hydrogel that is biologically similar to brain tissue (see: page 614, right column, lines 17-21; page 616, right column, and page 618, right column, lines 33-54) and thus does not contain any ingredient or property that would render it unsuitable for use in transplantation.
Regarding claim 3, Seo discloses that active components present in the extracellular matrix of the brain, such as collagen and glycosaminoglycan, are preserved in the decellularized extracellular matrix (see: page 613, left column, line 22-page 613, right column, line 20; page 614, right column, lines 17-21; and table 1). Since Seo is carrying out the same method steps as claimed and uses the same biological materials as claimed by Applicant and indicates that the active components present in the extracellular matrix of brain tissue are preserved, the final product is deemed to include the same properties baring evidence to the contrary.
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 4, Seo disclose wherein embryonic cortical neuronal cells are loaded in a decellularized extracellular matrix solution (see page 612, left column, line 48-page 612, right column, line 14, page 618) and also include induced neuronal cells (page 616, column 2).
Regarding claim 5, Seo disclose wherein the stretching device is an elastic material containing PDMS (page 612, column 2, Fabrication of the Chip).
Regarding claim 6, Seo disclose the feature wherein a tensile force is applied to a PDMS chip in the y-axis, so that microfibers are aligned in the x-axis direction (x-axis and y-axis are perpendicular) (see: page 612, right column, lines 48-52; page 617, left column, line 2-page 618, left column, line 2; and figure 5a).
Regarding claims 7-8, Seo disclose culturing the loaded induced neuronal cells after the tensile force is removed wherein the culture is performed within 21 days (less than 21 days) and at a temperature of 30-40 degrees C (37C)(page 612, column 2).
Therefore, the teaching of Seo et al anticipates Applicant’s invention as claimed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Seo et al (ACS Biomaterials Science and Engineering, published December 4, 2019).
Although the Seo reference cited above lists an inventor as one of the six authors of the reference, it is still applicable as prior art under 35 U.S.C. 102(a)(1).
Applicant may rely on the exception under 35 U.S.C. 102(b)(1)(A) to overcome this rejection under 35 U.S.C. 102(a)(1) by a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application, and is therefore not prior art under 35 U.S.C. 102(a)(1). Alternatively, applicant may rely on the exception under 35 U.S.C. 102(b)(1)(B) by providing evidence of a prior public disclosure via an affidavit or declaration under 37 CFR 1.130(b).
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Regarding claims 1-8, Seo discloses: a method for manufacturing a 3D culture scaffold, the method comprising the steps of: preparing a brain-derived decellularized extracellular matrix solution; applying a tensile force by using a tensioning device so that a polydimethylsiloxane (PDMS) chip is stretched; and loading the decellularized extracellular matrix solution on the stretched PDMS chip, followed by gelation, and restoring the PMDS chip to its original position, thereby manufacturing a 3D scaffold in which microfibers are isotropically aligned in a decellularized extracellular matrix; and a 3D scaffold in which microfibers are isotropically aligned in a decellularized extracellular matrix, the 3D scaffold being manufactured by the method (see: abstract, page 611, left column, line 34- page 611, right column, line 16; page 612, right column, lines 48-57; page 617, left column, line 2-page 618, left column, line 11; and figure 5а).
While Seo does not specifically state that the final 3D scaffold product is intended for transplantation, they do teach that the feature wherein a manufactured 3D culture scaffold provides an optimal microenvironment for the differentiation and growth of neurites by providing brain tissue-mimicking properties; and the feature wherein active components present in the extracellular matrix of the brain are preserved, thus having the advantage of providing a hydrogel that is biologically similar to brain tissue (see: page 614, right column, lines 17-21; page 616, right column, and page 618, right column, lines 33-54) and thus one of ordinary skill in the art would have been motivated to adapt the process and product to provide for the therapeutic use of transplantation with a reasonable expectation of success especially since Seo indicate that there is a need for therapeutic efficacy (page 616, column 2).
Seo discloses that active components present in the extracellular matrix of the brain, such as collagen and glycosaminoglycan, are preserved in the decellularized extracellular matrix (see: page 613, left column, line 22-page 613, right column, line 20; page 614, right column, lines 17-21; and table 1). Since Seo is carrying out the same method steps as claimed and uses the same biological materials as claimed by Applicant and indicates that the active components present in the extracellular matrix of brain tissue are preserved, the final product is deemed to include the same properties baring evidence to the contrary.
However, even, this were not the case and Seo’s extracellular matrix product does not necessarily include the same active components in the same concentrations as claimed, one of ordinary skill in the art would have been motivated to optimize the properties of the product to better mimic the natural environment as Seo indicate that there is a need for therapeutic efficacy (page 616, column 2).
Seo disclose wherein embryonic cortical neuronal cells are loaded in a decellularized extracellular matrix solution (see page 612, left column, line 48-page 612, right column, line 14, page 618) and also include induced neuronal cells (page 616, column 2). Seo disclose wherein the stretching device is an elastic material containing PDMS (page 612, column 2, Fabrication of the Chip). Seo disclose the feature wherein a tensile force is applied to a PDMS chip in the y-axis, so that microfibers are aligned in the x-axis direction (x-axis and y-axis are perpendicular) (see: page 612, right column, lines 48-52; page 617, left column, line 2-page 618, left column, line 2; and figure 5a). Seo disclose culturing the loaded induced neuronal cells after the tensile force is removed wherein the culture is performed within 21 days (less than 21 days) and at a temperature of 30-40 degrees C (37C)(page 612, column 2).
Therefore, while Seo appears to anticipate the claims as described above, even if this were not the case, one of ordinary skill in the art would have been motivated with a reasonable expectation of success to modify the product of Seo to include the claimed induced neuronal cells to the decellularized extracellular matrix that had been exposed to a tensile state by applying a tensile force to a stretching device as claimed because Seo teaches and suggests that the production of a composite brain dECM that mimics the natural environment and has been exposed to a tensile force provided by a stretching device is beneficial and desirable.
Therefore, the teaching of Seo et al renders obvious Applicant’s invention as claimed.
Claim(s) 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Reginensi et al (Tissue Engineering: Part A, epub March 2020) in view of Kim et al (Nature Communications 2017-from IDS filed 05/26/2023).
Regarding claims 1-6, Reginensi disclose a method of preparing a biomaterial, such as decellularized extracellular matrix, to potentiate the localization and efficacy of regenerative therapies (for transplantation) (abstract, page 66 Materials and Methods). The method includes a step for preparing a composition containing a decellularized matrix (page 966, column 2) and can be in hydrogel form (gel) (page 965, column 1, page 975, column 2) and suggested for use as a substrate for cells capable of differentiating into neuronal cells (induced neuronal cells) (page 966 column 1). The decellularized matrix is derived from brain tissue (page 966) and is mainly composed of hyaluronic acid, glycosaminoglycans, proteoglycans, ECM-affiliated proteins and ECM modulator (page 965, page 975, page 976).
While Reginensi are silent with regard to the concentration of the proteins in their decellularized extracellular matrix they are using decellularized extracellular matrix from the same tissue as claimed (brain) and are directed to obtaining a product that more closely replicates the in vivo environment and thus the claimed concentrations would be easily obtainable through routine optimization and experimentation.
With regard to the concentrations of the proteins in the decellularized extracellular matrix from brain tissue in the composition, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP 2144.05).
The selection of specific concentrations clearly would have been a routine matter of optimization and experimentation on the part of the artisan of ordinary skill, said artisan recognizing that the amount and viability of the cells cultured on the matrix substrate would have been affected by these concentrations.
Reginensi do not specifically teach a step for maintaining a tensile state by applying a tensile force to a stretching device made of an elastic polymer material and injecting the decellularized extracellular matrix composition into the stretching device and allowed to crosslink and removing the tensile force to align fibrils in the matrix in one direction.
Kim disclose methods to ansiotropically organize a three-dimensional culture platform for reconstruction of a neural network (Title, abstract) by applying anisotropic strain during fibrillogenesis of collagen to induce alignment of collagen fibrils by altering the shape of a pre-strained PDMS device containing collagen before the collagen is fully assembled and then allowed to return to its original configuration (page 2). The PDMS device is stretched by applying uniaxial strain along the y-axis and then the collagen solution is loaded into the device (injected) and fibrillogenesis is initiated and then the strain is released after a brief hold while the collagen is still in a sol/gel biphasic state and this induced a transformation of the viscoelastic collagen matrix confined in the device (pages 2-3, Figure 1). Kim also suggest wherein the tensile force acts in a direction perpendicular to the one direction of the process (page 2, column 2, page 3 Figure 1, page 4 column 2, pages 7-8 ). This method is taught to be adaptable to reconstruct normal neural circuits and can be useful when blended with patient-derived stem cell technology (page 10).
One of ordinary skill in the art would have been motivated to apply the method of Kim by maintaining a tensile state by applying a tensile force to a stretching device made of an elastic polymer material and injecting the decellularized extracellular matrix composition into the stretching device and allowing the matrix to crosslink and removing the tensile force to align fibrils in the matrix in one direction in the method of Reginensi because Kim teach and suggest that this method provides the benefit of normal neural circuits and can be useful when blended with patient-derived stem cell technology and Reginald is also directed to producing ECM products that can be used for neuronal cell therapy. The motivation in providing for crosslinking during the gelation process is that this is well known to provide a stronger and more stable matrix. One of ordinary skill in the art would have had a reasonable expectation of success because both Reginensi and Kim are directed to providing matrix derived products that reflect the in vivo environment of the neural tissue, such as the brain.
Regarding claims 7-8, Reginensi teaches and suggest that their decellularized extracellular matrix is beneficially cultured with neuronal cells for less than 21 days and at a temperature of 37 degrees C (page 966, page 968). The use of induced neuronal cells for tissue engineering is a well-known option in the art. One of ordinary skill in the art would have been motivated with a reasonable expectation of success to combine the culturing with the process of Kim because Kim indicates that their method is suitable for a culture platform.
Therefore, the combined teachings of Reginensi and Kim 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.
Chaikof et al., “Collagen Based Materials and Uses related Thereto”, US 2014/0193477.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631