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 .
Withdrawn Rejection
The rejection of independent claims 22, 23 and depending claims 5-17, under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, is withdrawn. The amendments to the claims remove the recitation of a first mixture and sequential mixing of the cells in the gel components. As such, the rejection is overcome.
The following rejection is necessitated by the amendments to the claims:
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 22 and 23, as well as dependent claims 5-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 22 and 23, the first recited step, “-bringing…”, has been amended to remove “into a first mixture”. As such, this step now more broadly recites, “-bringing primary human cortical cells (PHCCs) together with polyethylene glycol (PEG) or heparin” (claims 22) or “-bringing induced pluripotent stem cell-derived neuronal stem and progenitor cells (NSPCs) together with polyethylene glycol (PEG) or heparin” (claim 23). “Bringing…together” is a broader recitation than a “mixture” because cells can be brought into contact with PEG or heparin, brought into proximity with PEG or heparin, but not mixed and still meet the limitations of the “bringing…together” step. The second recited step states, as amended, “mixing the heparin or PEG cell mixture”. However, the previous “bringing” step does not require any type of mixture, just “bringing…together”. As such, the claims recite a broad limitation and then appears to refer back to the broad, “bringing…together” recitation with a narrower implication that it is a “mixture”. As such, the metes and bound of the claims are not apparent because it is not apparent if applicant intends to require the first “bringing…together” recitation to more narrowly be a “mixture” or not.
Claims 5-17 depend upon the claims 22 and/or 23. As such, they also comprise the above indefinite subject matter.
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.
(1) Claim(s) 22, 23, 9, and 12-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fruedenberg (Fruedenberg et al. Biomatierals 30 (2009) 5049-5060; of record in IDS 4/30/2024).
Regarding claims 22 and 23, Fruedenberg teaches producing a first solution comprising heparin that is then mixed with a 4-arm star-PEG solution to generate a hydrogel (p. 5050, col 2, section 2.1). Frudenberg teach that primary mouse NSC derived from cortical tissue (i.e. primary cortical cells and NSPCs), were seed into the hydrogel system and differentiated in the hydrogel systems by culturing with a defined media without mitogens but with forskolin and IL-1b (p. 5051, col 2, section 2.11). These teachings encompass bringing NSCP cells together with a mixture of heparin-star-PEG at the same time and culturing as claimed. Fruedenberg also teaches that they observed many Tuj1+ neurons showing mature axo-dendritic arboriztation (p. 5058, col 1), thus demonstrating neuronal differentiation, branching, and network formation.
As discussed above, Fruedenberg teaches bringing NSCP cells together with a mixture of heparin-star-PEG at the same time. Fruedenberg does not teach bringing the cells and a heparin or PEG together into a first mixture and then mixing the first mixture with a second gel component as claimed. However, the difference between the instant method and Fruedenberg is sequence of adding the cells to gel components (i.e. adding it the cells to one gel component and then adding a second gel component or adding the first gel component and the second gel component and then adding the cells). Determining when to add the cell to a gel mixture is well within routine optimization for one of skill in the art and is predictable. As such, it would have been obvious to artisan of ordinary skill to could from a finite period of times to added the cells to the gel components to predictably arrive at the limitations of claim 22 with a reasonable expectation of success. As such, claim 22 is an obvious variant of Fruedenberg.
Fruedenberg does not teach that the cells are human cells. However, Fredenberg does teach that the NSC hydrogels are intended for treating human diseases such as Parkinsons disease and clinical application (p 5050, paragraph bridging col 1 and 2). As such, the it would have been obvious to use HPCC or human NSC in the hydrogel of Frudenberg to predictably arrive at the limitations of the instant claims.
Regarding claim 9, Fruedenberg teaches functionalizing the star-PEG-heparin gel with RGD and and FGF-3 (p. 5050, col 2, sections 2.2 and 2.3 and scheme. 1).
Regarding claim 12, Fruedenberg teaches quantifying cell survival (p. 5056, figure 8C).
Regarding claim 13, Fruedenberg teaches monitoring axo-dendritic outgrowth of neurons over time (p. 5056, Figure 8 legend;).
Regarding claims 14-15, Fruedenberg monitor axo-dendritic outgrowth (pattern of formation of neurons and/or neural networks (figures 8 and 9). Claim 15 further recites, “for modeling diseases which have an effect in the human brain”. This is an intended use and therefore does not further limit the claimed method.
Regarding claim 16, Figure 9 discloses a monitors differentiation of the NSPCs into neuronal cells (i.e. change in plasticity). Claim 16 further specifies caused by disease-relevant protein aggregates. However, this is not an active step in the method and it does not specify what particular change, as any change encompasses this limitation.
Regarding claim 17, Fruedenberg determines the cells expressing neuron specific marker TuJ determining amount of differentiation that occurred (Figure 9).
In conclusion, Fruedenberg renders the instant claims obvious.
(2) Claim(s) 22, 23, 5, 6, 8, and 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fruedenberg (Fruedenberg et al. Biomatierals 30 (2009) 5049-5060; of record in IDS 4/30/2024) as applied to claims 22, 9, and 12-17 above, and further in view of Tsurkan (Macromolecular Rapid Communications 2010, 31, 1529-1533, of record in NPL 2/17/2021).
Regarding claim 22 and claim 5, Fruedenberg teaches the limitations of these claims as discussed above. Fruedenberg does not expressly teach bringing the cells in contact with a PEG or heparin into a first mixture that is then mixed with a second gel component that is PEG or heparin (claim 22), wherein the PEG is a star-PEG-heparin hydrogel which is cross linked via enzymatically cleavable peptide sequences, wherein the star-PEG-heparin hydrogel system is being cleaved and locally reconstructed.
However, Tsurkan teaches the in situ formation of star-PEG-peptide heparin hydrogels (page 2602, column 2, first full paragraph). Tsurkan teaches the heparin (HM6) was added to the cell suspension and then a PEG solution was then added to the solution of the heparin and cells (supplemental information (SI), page 5, bottom paragraph), meeting the limitations from claim 22 as discussed above.
Tsurkan teaches that the crosslinking the PEG-heparin hydrogel via enzymatically cleavable peptide sequences such as a metalloproteinase (MMP) cleavable sequence (page 2607, first column bottom paragraph), meeting the structural limitations recited in claim 5. Tsurkan further teaches by using enzymatically cleavable peptide linkers, the naturally functional heparin and the biocompatible and flexible PEG are crosslinked together into a covalent 3D network. By varying the degree of crosslinking, the viscoelastic characteristics and swelling of the hydrogel material can be controlled. The peptide linker used in this system is designed to be sensitive to the presence of MMPs, thus permitting the degradation and remodeling of the hydrogel material by cells secreting this enzyme (paragraph bridging pages 1529 and 1530). These teaches meet the limitations of the star-PEG-heparin hydrogel is being cleaved and locally reconstructed as claimed in claim 5.
Therefore, it would have been obvious to an artisan of ordinary skill to use the star-PEG-heparin hydrogel crosslinked using enzymatically cleavable MMP peptide sequences and the mean of making it admixed with cells, taught by Tsurkan, in place of the star-PEG-heparin hydrogel used in the method of Fruedenberg to predictably arrive at the limitations of claims 22 and 5. An artisan would have a reasonable expectation of success because Fruedenberg teaches that star-PEG heparin hydrogels support NSPCs differentiation into neural cells as claimed. Further an artisan would be motivated to use the star-PEG-heparin hydrogel system of Tsurkan in the method of Frudenberg because Tsurkan teaches using enzymatically cleavable peptide linkers, the naturally functional heparin and the biocompatible and flexible PEG are crosslinked together into a covalent 3D network. By varying the degree of crosslinking, the viscoelastic characteristics and swelling of the hydrogel material can be controlled. The peptide linker used in this system is designed to be sensitive to the presence of MMPs, thus permitting the degradation and remodeling of the hydrogel material by cells secreting this enzyme. As such, Fruedenberg in view of Tsurkan render claims 22 and 5 obvious.
Regarding claims 6, Tsurkan teaches the development of novel star-PEG- peptide conjugates with terminal thiol groups which can be utilized as nucleophiles in Michael addition reactions with electron deficient double bond-containing components (Scheme 1) (page 2602, column 2, first full paragraph). Tsurkan discloses the Star- PEG-peptide conjugates were subsequently crosslinked using commercially available maleimide-terminated star-PEG molecules (page 2607, second column, last paragraph). Thus, Fruedenberg in view of Tsurkan render claim 6 obvious for reasons discussed above.
Regarding claim 8, Tsurkan teacher the hydrogel matrix could be tuned by increasing the ratio of star-PEG to heparin leading to a hydrogel with a higher storage modulus, and that hydrogels of varying stiffness, approximately 200PA to 6000Pa, could be formed(page 2608, second column). Tsurkan teaches a hydrogel having a storage modulus of from 0.100-0.600 kPa (figures 2A, 2B), teaching a range encompassing the claimed “range of from 300-600 pascals” . Thus, Fruedenberg in view of Tsurkan render claim 8 obvious for reasons discussed above.
Regarding claim 9, Tsurkan discloses the star-PEG-heparin hydrogel system is modified with RGD peptides, which are peptide units derived from proteins of the ECM in Figure 2D (the claimed “signaling molecules and/or with functional peptide units derived from proteins of an extracellular matrix (ECM).”
Tsurkan discloses (figure 2) the storage modulus of starPEG-heparin gels, a modulus of about 300-600 PA. Tsurkan discloses by varying the degree of crosslinking, the viscoelastic characteristics and swelling of the hydrogel material can be controlled (the claimed “wherein the hydrogel is characterized by a storage modulus which is determined by a molar ratio of PRG to heparin;” claim 20, last part). Thus, Fruedenberg in view of Tsurkan render claim 9 obvious for reasons discussed above.
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A, B, E, F and G are applicable. The claimed method was known in the art at the time of filing as indicated by Fruedenberg in view of Tsurkan. Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
(3) Claim(s) 22, 23, 5 and 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fruedenberg (Fruedenberg et al. Biomatierals 30 (2009) 5049-5060; of record in IDS 4/30/2024) as applied to claims 22, 5, 6, 8, 9, and 12-17 above, and further in view of Tsurkan (Macromolecular Rapid Communications 2010, 31, 1529-1533, of record in NPL 2/17/2021) and Wieduwild et al (“Minimal Peptide Motif for Non-covalent Peptide- Heparin Hydrogels, JACS 2013, 135, 2919-2922).
Regarding claims 22, 5, and 7, Fruedenberg in view of Tsurkan teaches the limitations of the claims as discussed above. Fruedenber in view of Tsurkan does not teach alternative wherein the hydrogel system is formed non-covalently from heparin and a covalent star-PEG-peptide conjugate comprising conjugates of two or more peptides which are coupled to a polymer chain and the peptide sequence contains a repeating dipeptide motif (BA)n, where B is an amino acid having a positively charged side chain, A is Ala and n is a number from 5 to 20.
However, Wieduwild teaches a system based on peptide motifs can be used to design tunable, non-covalent polymer matrices and that networks based on heparin are of particular interest because of their ability to bind many important signaling molecules (page 2919, left column, first paragraph). Wieduwild teaches the motif (BA)n (page 2920, left column, top paragraph), where B is a basic residue, either arginine or lysine. Wieduwild teaches that the thiol group of cysteine was used to couple the peptides to maleimide-functionalized 10 kDa starPEG by Michael-type addition reactions(page 2920, left column, second paragraph). Wieduwild teaches to test for hydrogel formation, these conjugates were mixed with 14 kDa heparin at a 1:1 ratio in physiological phosphate buffer (PBS) (Scheme 1, Figures S3 and S4) (page 2920, left column, second paragraph), teaching the claimed “hydrogel self-organization.” Wieduwild teaches the RA7-starPEG, KA5-starPEG, and KA7- star-PEG formed stable hydrogels with heparin and had a wide range of stiffness levels (Table 1) (page 2920, left column, third paragraph). Wieduwild teaches other attributes of the KA7-star-PEG-heparin hydrogels such the ability to keep in PBS and cell culture medium for months (page 2920, left column, last paragraph). Wieduwild teaches the (BA)n amino acid motif was found to have a very simple S/F relationship through mutational studies in which “function” refers to the assembly of the peptide-starPEG conjugate and heparin into a hydrogel (page 2920, right column, top paragraph). Wieduwild teaches the relationship is governed by the following rules: (1) At least five repeats of the (BA), motif are required for the assembly of the peptide-starPEG conjugate with heparin and that increasing the number of (BA)n repeats results in stiffer gels (Table Il). Seven repeats of either the KA or RA motif produce stiffer hydrogels than do 5 repeats. If the same number of repeats is used, the (KA), peptides generate hydrogels that are stiffer than those from the (RA), peptides. (2) The heparin induced a-helix formation is necessary for the assembly process (Figures la and S6d, Tables 1 and S2). Wieduwild teaches heparin and KA7— starPEG or heparin and KA5—starPEG formed hydrogels more slowly (page 2921, left column, third full paragraph). Wieduwild teaches that by changing the heparin and/or peptide—starPEG concentrations, the mechanical properties can be further tuned over more than an order of magnitude and that, remarkably, at a concentration as low as 0.5 mM, heparin can still form a hydrogel with KA7—starPEG (2.5 mM) (page 2921, right column, top paragraph). Wieduwild teaches that because of the relatively rapid gelation, 5 mM KA7—starPEG and 5 mM heparin provided the optimal reagents for cell embedding (page 2922, left column, top paragraph). Wieduwild teaches simple variables govern a highly flexible system that can easily be tuned by changing the number of (BA), repeats, by adjusting the concentration of each component, or by introducing simple mutations and that, importantly, stable hydrogels can be formed in the presence of large quantities of cells in cell culture medium at 37 °C, and cells embedded within the non-covalent hydrogel survive and are metabolically active(page 2922, left column, last full paragraph). Wieduwild thus teaches the (BA)n peptides comprising 7 dipeptide residues, a number falling within the claimed range of 5 to 20 (claim 7). It would have been obvious to one of ordinary skill to choose that number of (BA)n repeats in order to obtain a stable hydrogel gel system suitable for the growth of desired cell types.
Therefore, it would have been obvious to one of ordinary skill to modify the hydrogel in the culture method of Freudenberg in view of Tsurkan (covalent star-PEG-heparin hydrogel system) by using the (BA)n peptide as suggested by Wieduwild in view of the teachings of Wieduwild that stable hydrogels comprising the (BA)n motif can be formed in the presence of large quantities of cells in cell culture medium at 37 °C, and cells embedded within the non-covalent hydrogel survive and are metabolically active to predictably arrive at the limitations of claim 7. One of ordinary skill would have had a reasonable expectation of success in modifying the culture method of Tsurkan by including the BA(n) peptide in the PEG-heparin hydrogel view of the teachings of Wieduwild that the cells embedded therein are metabolically active. One of ordinary skill in the art would have been motivated to utilize a cell culture system optimizing cell growth and sustainably maintaining large cell numbers in order to facilitate development of cell model systems. Thus, Fruedenberg in view of Tsukan and Wieduwild render claim 7 obvious.
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A, B, E, F and G are applicable. The claimed method was known in the art at the time of filing as indicated by Freudenberg in view of Tsurkan and Wieduwild. Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Declaration Consideration
The declaration under 37 CFR 1.132 filed 10/29/2025 is insufficient to overcome the rejection of claims 5-17 and 22-23 based upon 35 USC 103(a) as set forth in the last Office action because: The declaration does not demonstrate that the breadth of the claimed invention is not an obvious variant of the recited prior art in the rejections of record.
The declaration submits that Examiner’s interpretation of Freudenberg teaching a seeding mouse NSC into the hydrogel system and differentiating in the hydrogel system is incorrect. In Freudenberg all cell cultures were only performed by seeding cells on top of the surface bound hydrogels (see p. 2, section 7). Freudenberg neither embedded cells within the hydrogel nor mixed them with any of the hydrogel precursors. (see p. 3, section 8). Freudenberg conducted a 2D cell culture on top of the hydrogel and never reported on neuronal network formation within the volume phase of the hydrogel (see p. 3, section 9). The declaration states that the differentiation of NSC on a gel surface has been achieved in the prior art numerous times and proceeds via a different mechanism than occurring in a 3D hydrogel system as claimed (p. 2, sections 10 and 11). The declaration submits that a person of ordinary skill would not have expected that replacing mouse NSPCs with human NSPCs or iPSC, and embedding them within a dense starPEG-heparin gel rather than cultivating them on top of it, would enabled the formation of mature neuronal networks throughout the hydrogel volume, including functionally active neurons. The declaration submits this is a surprising effect of the present application (p. 4 section 12). Freudenberg addresses the potential application of the gels for Parkinson’s disease in the context of biocompatibility testing and grafting behavior of the cell free hydrogel, in order to evaluate the biocompatibility of the material in the rat striatum (p. 4, section 13). The declaration concludes that nothing in the cited work would provide a skilled person with any reasonable expectation of success in achieving the formation of the claimed 3D hydrogel (p. 4, section 14).
In response, while the declaration indicates the invention of the instant application is different from Freudenberg, the invention of the claims is generically recited and as such still encompasses an obvious variant of Freudenberg. The claims as amended require the active step of “bringing” PHCC or NSPC “together with” PEG or heparin. This step does not require any mixing or placing the cells in PEG or heparin solution, only bringing the cells together with the PEG or heparin. Also while PEG or heparin are recited in the alternative, “or” does not exclude bring cells into together with PEG and heparin because “and” encompass contacting PEG and contacting heparin individually as well. The second recited active step recites, mixing the heparin or PEG cell mixture with a second gel component of PEG or heparin and formong the hydrogel that contains PEG, heparin and the cells. As previously stated in the indefiniteness rejection above, no clear mixture of cells and PEG or heparin occurs in the first active step and the second recited does not recite any specific limitations that require a first solution that has cells mixed or dispersed through solution and then adding an additional solution that is not the first solution that is heparin or PEG sequentially. As such, the generic nature of first two active steps is in any manner bringing the cells, the PEG, and the heparin together to result in a hydrogel that “contains” PEG, heparin, and the cells is formed. “Contains” similar to “comprising” is open transitional language and therefore does not limit the cells to being embedded or dispersed in the hydrogel. As such, the cells can also have the configuration of being seeded on or in the hydrogel. The last recited step actively requires “culturing the cells within the hydrogel system…such that the cells within the hydrogel system generate a network of neuronal and glial cells I a three-dimensional arrangement”. In this recitation, one would understand that “the hydrogel system” refers back to the hydrogel comprising the cells. Given the language of the previous step are generic with no clear implication of embedding the cells in the hydrogel, the term “within” must be given a broad interpretation, such as within the confines of the hydrogel system. Regarding the intended end-product of network of neuronal and glial cells in a three-dimensional arrangement, the network is generically claimed because the claim does not specify any particular structural limitations of the network other than the neuronal and glial cells are part of the network that they are present in any three dimensional arrangement. The specification does not define three dimensional arrangement; thus it must be given its broadest reasonable interpretation, meaning the network of cells has length, width, and height.
Given the broadest reasonable interpretation, many of the cited limitations that the declaration states distinguish the invention of the application from Freudenberg are not required by the claims. As discussed above, the declaration regards the system of Freudenberg as a “2D system” (section 11) because the cells are cultured on the surface of the gel. However, the fact is that the system of Freudenberg is actually a 3D system because the cells and the hydrogel have length, width, and volume. The declaration states the differentiation and axo-dendritic outgrowth of mouse NSCs are the surface of the gel or on other two-dimensional culture substrates (section 10). Such statements are defining a 3D in contrast to a 2D culture, which is not required by the claims. The hydrogel described by Freudenberg comprises differentiation and axo-dendritic outgrowth and glial cells all of which have dimensional of length, width and height and can be considered a network.
The declaration makes the distinction of the cells being “seeded” on the surface of the hydrogel, taught in Freudenberg, and being “embedded” in the hydrogel in the invention of the instant application. As discussed above the claims do not require “embedded” and do not clearly require mixing the cells into the hydrogel in the first two active steps as discussed above. As such, the claims could still encompass seeding as expressly recites by Freudenberg. Further, even if one were to limit the interpretation of the cells “within” the hydrogel to mean that the cells are required to be inside the hydrogel, dispersed in, or embedded in the hydrogel. One of ordinary skill could choose from a finite number of predictable, possible variations of bringing the hydrogel and cells together to predictable arrive at mixing the cells in solution in the precursor solution or a PEG/heparin hydrogel solution prior to solidification using routine art established methods.
The declaration submits a lack of reasonable expectation of success or predictability at arrive at the end product of the hydrogel with its network of cells. Examiner does not agree because of the generic way that the end-product is claimed. Again the declaration appears to be imparting structure to this end-product that is not claimed. The declaration suggest that the structure of the 2D method of Freudenberg is different from the 3D structure in the present application. However, the generic nature of the claimed hydrogel comprising the network does not capture such a distinct. The claims as written solely require end-product of a hydrogel comprising a network of of glial and neuronal cells that has height, width, and length. Freudenberg provides such an end-product as generically claimed and thus would be predictable and not a surprising result.
Regarding the declaration discussion of Parkinson’s disease for motivation to use human cells in the hydrogel as opposed to mouse cells as used in Freudenberg, Freudenberg clearly eludes to a use of the hydrogel design for humans such as possibly in the case of use with Parkinson disease. The motivation is discussing why one would use human cells instead of mouse cells in the culture system, not motivation for therapeutic use in Parkinson’s disease. It is well established that these types of gels are not only intended to be used in mice but for cell therapies in humans. Freudenberg’s discussion provides evidence for this desired use of human cells in hydrogels. Further, the reasonable expectation of success hinges on whether one would reasonably expect that human cells can be placed on or within the gel and form the network as generically claimed. Given the claims only require the glial and the neuronal cells are both present in any type of arrangement that has length, width, and height, the disclosure by Freudenberg showing that neuronal cells and glial cells are present in an arrangement that has length, width and height, one would reasonably expect human cells to predictable form a generic network as claimed.
Thus in conclusion, the declaration is insufficient to overcome the obviousness rejections of record because the claims are generic in nature and still encompass the limitations or an obvious variation of Freudenberg as claimed. Examiner does recognize that the hydrogel system described in the application may have a different structure than Freudenberg. However, at this moment the claims do not capture such a difference.
Response to Arguments
Applicant's arguments filed 10/10/2025 have been fully considered but they are not persuasive.
Applicant submits that Freudenberg does not mix the cells with hydrogel precursor solutions and does not teach embedded cells within the hydrogel. Applicant refers the declaration as suggest for this assertion.
In response, the claims do not recited mixing the cells in hydrogel precursors and embedding cells within the hydrogel. As such, these limitations are not required. The declaration and discussion thereof further address this above.
Applicant submits that the Examiner has not shown any motivation or suggestion within Freudenberg which would lead to the content of claims 22 and 23. In response, Applicant is referred back to the rejection which provides express motivation. Further, Examiner addresses motivation further above in the discussion of the declaration. As such, Applicant is directed above.
Applicant submits that Tsurkan II does not teach the claimed network. In response, Tsurkan II was not provided for such teaching and given the generic nature of the claimed network, one would have a reasonable expectation of Freudenberg in view of Tsurkan II would form the generic network structure. See declaration discussion above as to the generic interpretation of the claimed network.
Applicant submits that that Examiner only provided a shorthand analysis of motivation to combined the secondary references with the Freudenberg and thus did not provide adequate obviousness statements.
In response, Examiner did provide description of KSR rationales but then further provide expressly written obvious statements that describes exactly how the references would be combined, expressly describe why one would have a reasonable expectation of success in that particular combination of the prior art, and motivations from the prior art references for combining the references as such. See page 8, lines 3-8; paragraph bridging pages 10 and 11; and paragraph bridging pages 15 and 16 of the previous office action.
In conclusion, the obviousness rejections are maintained because the amended claims are still taught by the disclosed prior arts and Applicant’s argument were not persuasive in overcoming the rejections.
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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MARCIA S. NOBLE
Primary Examiner
Art Unit 1632
/MARCIA S NOBLE/ Primary Examiner, Art Unit 1632