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 .
This action is responsive to papers filed 12/01/2025.
Claims 1 and 3 have been amended. Claims 41-43 have been newly added and claim 23 has been newly canceled.
Claims 1-8, 10-11, 15-18, 21, 28-29, 32-33, and 39-43 are currently pending.
Claims 4, 6-8 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected specie, there being no allowable generic or linking claim. Election of the specie of pancreas for the target tissue (target internal organ) was made without traverse in the reply filed on 12/09/2020.
Claims 1-3, 5, 10-11, 15-18, 21, 28-29, 32-33, and 39-43 have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application No. 62/518,380 and Application No. 62/664,694, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Claim 1 requires “wherein the second hydrogel has a viscoelasticity from 250 to 800 Pa”. The prior filed applications do not disclose a viscoelasticity range of 250 to 800 Pa and thus the claimed invention is not entitled to the filing date of these applications.
The non-provisional application does provide support for the amended claims and therefore claim 1 and dependent claims 2-3, 5, 10-11, 15-18, 21, 28-29, 32-33, and 39-40 have been examined with the effective filing date of the non-provisional which is 06/12/2018.
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 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.
Claims 1-3, 5, 10-11, 15-18, 21, 28-29, 32-33, 39-43 are rejected under 35 U.S.C. 103 as being unpatentable over Mooney et al (US 2008/0044900-from IDS filed 11/14/2018) in view of Reid et al (US 2014/0301985-previously cited), Ghosh et al (Biomaterials, 2007-from IDS filed 02/17/2021) and Hanjaya-Putra et al (US 2012/0225814-from IDS filed 11/14/2018).
Regarding claims 1-3, 5, 10-11, 40, Mooney teach a cell transplantation device that contains a mixture of cells and can be used for organ and tissue regeneration (page 3 para 17) repair and augmentation of function of a mammalian bodily tissue (page 3 para 19). The mixed cells may include stem cells such as mesenchymal stem cells (MSCs, early lineage stage cell-ELSMCs) and pancreatic stem cells (epithelial stem cells) (page 3 para 17 and page 6 para 44). As per Applicant’s disclosure, MSCs are early lineage stage cells capable of expressing and secreting MMPs (see page 36 lines 14-21 of Applicant’s specification). This device includes a scaffold composition which incorporates or is coated with a bioactive composition, the device regulates the egress of resident cells through the physical or chemical characteristics of the scaffold. The scaffold can be differentially permeable, allowing cell egress (migration) only in certain physical areas of the scaffold. The permeability of the scaffold composition is regulated by selecting or engineering a material for viscoelasticity (page 1 para 6). This would render obvious a material configured to inhibit cell migration towards an undesired direction, away from the target tissue and towards the backing material.
Mooney include wherein their polymeric carriers include a mesh (pages 12-13 para 79) and specifically wherein the scaffold is porous (page 2 para 16, page 7 para 49) and fabricated from a variety of polymers including a hydrogel and hyaluronic acid (hyaluronan) (page 8 para 51-52).
The scaffold is biocompatible and biodegradable (page 2 para 13). The cells incubated in the scaffold are educated and induced to migrate out of the scaffold to directly affect a target tissue, e.g. an injured tissue site (page 7 para 47-48). The cells may include a hydrogel medium that contains factors required to maintain the multipotent nature of stem cells (maintain sternness) (page 10 para 68-69) and/or inhibit differentiation (para 11, page 7 para 48, para 81, para 85, para 93). Suitable hydrogels are taught to be well known in the art (page 10 para 66) and include hydrogels with hyaluronic acid (hyaluronan) (page 8 para 52, page 13 para 82).
Mooney disclose wherein MMP-sensitive substrates are used to allow cells to exit when the seeded cells have secreted sufficient MMP to begin degradation of the matrix (page para 46). This provides for wherein at least the first hydrogel is configured to allow the mixed cell population to produce an amount of MMPs sufficient to allow the cells to exit the hydrogel and facilitate engraftment of cells into target internal organs.
Mooney does not specifically disclose an embodiment wherein the target internal organ is brought into contact with the device delivering mesenchymal stem cells and epithelial stem cells into the target internal organ nor an embodiment wherein the target internal organ is the pancreas.
Reid teach a method of treating a pancreatic disfunction by administering a mixture of pancreatic stem cells, mesenchymal stem, progenitor cells and biomaterials such as hyaluronan to pancreatic tissue (pages 2-3, para 14-16). The grafting technologies that involve the delivery of transplanted cells as an aggregate on or in scaffolds that can be localized to the diseased tissue to promote proliferation and engraftment is explicitly taught (page 6 para 47). Applicant’s specification indicates that cell organoids include cell aggregates (page 28).
One of ordinary skill in the art would have been motivated to select the pancreatic organ as the target tissue injured by diseases such as diabetes because Reid suggest that such injured pancreatic organ tissue is in need of repair and would benefit from delivering a mixture of pancreatic stem cells, mesenchymal stem, progenitor cells and biomaterials such as hyaluronan (pages 2-3, para 14-16). One of ordinary skill in the art would have had a reasonable expectation of success in applying the method of Mooney to injured pancreatic tissue and administering MSCs and pancreatic stem cells directly to the pancreas because Mooney suggests that damaged pancreatic tissue is a suitable organ tissue type for their method and Mooney also includes the use of a mixture of stem, progenitor and pancreatic stem cells in their composition as well and that they are capable of ensuring that the cells included in their device maintain their stemness.
Mooney teach wherein the mixed cells may include adult stem cells, mesenchymal stem cells (MSCs, early lineage stage cell), pancreatic stem cells, pancreatic islet cells, epithelial cells (page 3 para 17 and page 6 para 44).
Reid suggest that such injured pancreatic organ tissue is in need of repair and would benefit from delivering a mixture of pancreatic stem cells, mesenchymal stem, progenitor cells and biomaterials such as hyaluronan (pages 2-3, para 14-16) providing motivation to deliver the cell mixture directly to the pancreatic organ tissue. Reid also teach that biliary tree stem cells (BTSCs) can give rise to either liver or pancreas (page 3 para 24) and thus these cells would be obvious for use in the repair of pancreatic tissue as pancreatic progenitor cells or pancreatic stem cells. One of ordinary skill in the art would have also been motivated to include BTSCs in Mooney with a reasonable expectation of success because Mooney also suggest the inclusion of adult stem cells in their method that give rise to the pancreas as well.
Regarding step c of claim 1, Mooney teach addition of a first and second hydrogel coating (page 10 para 69) and compartment layers (pages 10-11 para 70-71) to control the cells. The release profiles from the scaffold devices are controlled (configured) by both factor diffusion and polymer degradation, the dose of the factor loaded in the system and the composition of the polymer (page 12 para 78). With migration away from the target tissue being discouraged, the addition of a third hydrogel layer on the opposite side (serosal surface) of the backing away from the cells would be obvious to reinforce the backing of the scaffold and prevent cells from migrating away from the target tissue. One of ordinary skill in the art would have had a reasonable expectation of success because Mooney specifically suggests adding layers to regulate cell locomotion (migration) (page 3 para 18) and outer coverings (backings) (page 24 para 154). The mere duplication of parts has no patentable significance unless a new and unexpected result is produced (MPEP 2144.04 VI).
With regard to the inhibition or prevention of adhesions by or from other tissues, this property is deemed to be present when using the same polymer (hyaluronan) and designed to have a viscoelasticity to inhibit migration of the cells away from the target tissue baring evidence to the contrary. Mooney teach that they utilize materials with a relatively low elastic modulus, e.g., 0.1-100, 1-100kPa (e.g. 100 Pa, 1,000 Pa are included at the low end of these ranges) and that this is why they include hydrogels and elastomeric polymers (page 24 para 154). Applicant’s Specification states that a hyaluronan hydrogel with a viscoelasticity of approximately 106 Pa has a level of rigidity that it served to further minimize adhesions from neighboring tissues (see page 77 lines 15-19 of Applicant’s Specification).
Regarding claims 1, 39, Mooney teach that they utilize materials with a relatively low elastic modulus, e.g., 0.1-100, 1-100kPa (e.g. 100 Pa, 1,000 Pa are included at the low end of these ranges) and that stiff materials would not be suitable, as such materials would not conform to a wound and that this is why they include hydrogels and elastomeric polymers (page 24 para 154). Mooney discloses that the scaffold may be composed of multiple gel layers of various levels of rigidity and form a sandwich configuration” (pages 10-11 para 63-71).
Mooney do not explicitly recite the claimed viscoelasticities for the various layers.
Ghosh examines the effects of viscoelastic properties of hyaluronan/fibronectin hydrogels on cell behavior (Abstract). Ghosh discloses preparing hydrogels with viscoelasticity of 95, 550 and 4270 Pa and seeding human dermal fibroblasts (hDFs) on the hydrogels (Section 2.1,2.4). hDF migration speed significantly decreased as viscosity of the hydrogel increased (Section 3.3.1, Fig. 5). Ghosh suggests that softer hydrogels (e.g., 95 Pa) may be utilized to promote cellular migration, while viscosities of 550 Pa or higher promote cellular adhesion and proliferation (Section 3.3.1,4, Fig. 5).
Hanjaya-Putra teach the viscoelasticities of hydrogels (including hyaluronic acid) intended for use in regenerative medicine (page 2 para 10, para 17, page 3 para 35) and indicate that values of 650 +/- 180 Pa provide a rigid hydrogel, 75 +/-40 Pa for a firm hydrogel and 10+/-2 Pa for a yielding hydrogel (page 3 para 35). Cell migration is discussed as well (page 7 para 77, page 8 para 87, para 91, page 9 para 92, page 15 para 153, pages 18-19, para 180).
As Mooney, Ghosh and Hanjaya-Putra are all directed to hyaluronan based hydrogels and cellular migration therein by modulating physical characteristics of the hydrogel, it would be obvious to one of ordinary skill in the art that the references could be combined. A skilled artisan would be motivated with a reasonable expectation of success to utilize the viscoelasticities suggest by Ghosh and Hanjaya-Putra because they fall within the range of viscoelasticities suggested by Mooney to both promote and inhibit cellular migration within the hydrogel. Softer hydrogels of about 95 Pa would be utilized in the first hydrogel where cell migration toward the target tissue is desired (configured to allow the mixed population comprising MSCs and BTSCs to produce an amount of MMPs in the first hydrogel sufficient to facilitate engraftment of the BTSCs into the target tissue).
More firm hydrogels of about 500 Pa would be more desirable for the second and third hydrogels so that they can prevent egress of the administered cells away from the target tissue. A third hydrogel with a viscoelasticity of about 500 Pa would also inherently inhibit adhesions by or from other tissues or organs as per Applicant’s Specification (see page 61 lines 1-9, page 68 lines 9-16, page 77 lines 15-19).
Regarding claims 15-17, 40, Mooney suggests wherein the hydrogels are made from hyaluronic acid (hyaluronan)(page 8 para 51-52).
Regarding claim 18, the cells may include a hydrogel medium that contains factors required to maintain the multipotent nature of stem cells (maintain sternness) (page 10 para 68-69).
Regarding claims 21, Mooney teach wherein the mixed cells may include adult stem cells, mesenchymal stem cells (MSCs, early lineage stage cell), pancreatic stem cells, pancreatic islet cells, epithelial cells (page 3 para 17 and page 6 para 44). Reid suggest that such injured pancreatic organ tissue is in need of repair and would benefit from delivering a mixture of pancreatic stem cells, mesenchymal stem, progenitor cells and biomaterials such as hyaluronan (pages 2-3, para 14-16) providing motivation to deliver the stem cells directly to the pancreatic organ tissue. Reid also teach that biliary tree stem cells (BTSC) can give rise to either liver or pancreas (page 3 para 24) and thus these cells would be obvious for use in the repair of pancreatic tissue as pancreatic progenitor cells or pancreatic stem cells.
Regarding claim 28, Mooney teach wherein the cells are autologous or allogeneic (page 14 para 92).
Regarding claim 29, Mooney teach wherein the cells are programmed/reprogrammed (genetically modified) (page 15 para 97).
Regarding claim 32, Mooney teach wherein the scaffold (backing) comprises a nonporous material such as metals and silk (page 2 para 13, page 24 para 154).
Regarding claim 33, Mooney teach wherein the scaffold (backing) includes materials that have sufficient resilience to withstand mechanical forces, able to be tethered to a target organ or tissue and has sufficient flexibility to be tethered to locations with curvature (such as a liver) (page 7 para 49, page 24 para 154).
Regarding claims 41-43, Mooney does not specifically teach including organoids in their method and are silent with regard to the number of cells included in their cell mixture.
Reid teach a method of treating a pancreatic disfunction by administering a mixture of pancreatic stem cells, mesenchymal stem, progenitor cells and biomaterials such as hyaluronan to pancreatic tissue (pages 2-3, para 14-16). The grafting technologies that involve the delivery of transplanted cells as an aggregate on or in scaffolds that can be localized to the diseased tissue to promote proliferation and engraftment is explicitly taught (page 6 para 47). Applicant’s specification indicates that cell organoids include cell aggregates (page 28). Reid also teach that biliary tree stem cells (BTSCs) can give rise to either liver or pancreas (page 3 para 24) and thus these cells would be obvious for use in the repair of pancreatic tissue as pancreatic progenitor cells or pancreatic stem cells.
While Mooney and Reid are silent with regard to the total number of cells and cell aggregates to include in their administered cell graft compositions, these cell and organoid numbers would have been a matter of routine optimization and experimentation. The optimal cell and organoid amount would have been dependent upon the size of the subject and the size and severity of the damaged organ tissue. Target damaged organs from larger mammals would require larger amounts of cells than lab animals such as mice. The fact that Mooney includes an example wherein their scaffold is seeded with 107 cells/ml (page 21 para 138) is suggestive that scaffolds with at least 107 cells would be appropriate. The number of aggregates (organoids) from these cells would be affected by the need to keep the aggregates of a small size in order to avoid cell necrosis that occurs when cell aggregates get too large and thus a larger number of aggregates from 107 cells (at least 100,000 aggregates or organoids) would be appropriate.
With regard to the concentrations of cells 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 would have been affected by these concentrations.
The combined teachings of Mooney et al, Reid et al, Ghosh et al and Hanjaya-Putra et al render obvious Applicant’s invention as claimed.
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 5, 10-11, 15-18, 21, 28-29, 32-33, and 39-43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 47 of copending Application No. 17/867135 in view of Mooney et al (US 2008/0044900-from IDS filed 11/14/2018), Reid et al (US 2014/0301985), Ghosh et al (Biomaterials, 2007-from IDS filed 02/17/2021) and Hanjaya-Putra et al (US 2012/0225814-from IDS filed 11/14/2018).
The claim of the copending application is drawn to a method of engrafting cells into a target tissue comprising contacting the target tissue with a patch graft composition comprising a mixed population having two or more cell types, including early lineage stage cells capable of expressing MMPs in a medium in a first hydrogel having viscoelasticity sufficient to allow for migration of the mixed population into the target tissue and a backing comprising a biocompatible, biodegradable material having a viscoelasticity sufficient to inhibit a migration of the mixed population away from the target tissue.
The copending claim does not specifically include all the claimed features in one embodiment and wherein the cells include biliary tree stem cells.
Mooney and Reid render obvious pancreatic tissue as a target tissue for a patch graft, the inclusion of multiple cell types and multiple layers and suggest the inclusion of biliary tree stem cells as described above. Mooney and Reid also render obvious the inclusion of aggregates (organoids), organoid number and a cell number of at least 107 cells as described above.
Gosh and Hanjaya-Putra render obvious the ranges of viscoelasticity in the hydrogel layers as described above.
Therefore, the combined teachings Mooney et al, Reid et al, Gosh et al and Hanjaya-Putra et al and the copending claim render obvious Applicant’s invention as claimed.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 12/01/2025 have been fully considered but they are not fully persuasive.
Applicant argues that the cited references do not teach or suggest that the first hydrogel is configured to allow the mixed population comprising ELMSCs and BTSCs to produce an amount of MMPs in the first hydrogel sufficient to facilitate engraftment of the BTSCs into target internal organ. Applicant asserts that their studies offer evidence for entirely new roles of MMPs that contribute to engraftment, migration and integration of transplanted cells. Applicant refers to their working examples as evidence.
This is not found persuasive. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Mooney disclose wherein MMP-sensitive substrates are used to allow cells to exit when the seeded cells have secreted sufficient MMP to begin degradation of the matrix (page para 46). This provides for wherein the first hydrogel (which contains cells) is configured to allow the mixed cell population to produce an amount of MMPs sufficient to allow the cells to exit the hydrogel and facilitate engraftment of cells into target internal organs.
Applicant argues that neither Mooney nor Reid teach or suggest the mixed population of ELSMCs and BTSCs. Applicant asserts that Mooney is limited to the differentiation of stem cells in the device and does not teach or suggest engrafting undifferentiated stem cells.
This is not found persuasive. First, the obviousness rejection is based on the combination of references and not on the teaching of Mooney alone. Reid provides the teaching, suggestion and motivation to administer various types of stem cells to the target organ tissue as described above. Second, Mooney does not specifically require that only differentiated cells are administered with their device and provide for ways in order to keep the cells from differentiating. Third, Mooney also specifically states that while their invention has been particularly shown and described with reference to preferred embodiments that it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention (page 25 para 164). Therefore, the method of Mooney is not limited to their disclosed examples.
Applicant asserts that Mooney does not provide guidance for selecting a viscoelasticity as claimed. Applicant asserts that Mooney is limited to soft materials described at paragraph 154 within Example 3 and transplanting of myoblasts in this specific example.
This is not found persuasive. First, the obviousness rejection is based on the combination of references and not on the teaching of Mooney alone. Second, Mooney discloses that a scaffold may be composed of multiple gel layers of various levels of rigidity and form a sandwich configuration (pages 10-11 para 63-71). Third, Mooney also specifically states that while their invention has been particularly shown and described with reference to preferred embodiments that it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the scope of the invention. Therefore, the method of Mooney is not limited to their disclosed examples.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that Ghosh and Hanjaya-Putra are not relevant to the claimed invention. Applicant asserts that Gosh is limited to developing hydrogels for wound repair and only shows the different viscoelastic properties of hydrogels on dermal fibroblasts and Mooney does not provide sufficient guidance for selecting biomaterials and appropriate viscoelasticity ranges for pancreas or liver. Applicant argues that because Gosh only measures cell migration within the hydrogel in their example at page 54 that they cannot be applied to Applicant’s claims which recite cell migration out of the hydrogel and into the target organ or tissue. Applicant asserts that the success of cellular migration out of the hydrogel into the target depends on the characteristic of the hydrogels to maintain cellular MMP expression, which is not taught or suggested by Gosh. Applicant asserts that because of this that Gosh is not relevant to the claimed invention and cannot provide the missing teaching of Mooney.
This is not found persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Mooney teaches that their method and device are suitable for multiple cell types and a viscoelasticity range that overlaps with Gosh. Ghosh suggests that softer hydrogels (e.g., 95 Pa) may be utilized to promote cellular migration, while viscosities of 550 Pa or higher promote cellular adhesion and proliferation (Section 3.3.1,4, Fig. 5).
The Mooney reference specifically indicates that their method uses the softer hydrogels (page 24 para 154) and that the cells egress (migration) from the hydrogel is to be controlled (page 1 para 6). Applicant has not provided any evidence that the references are missing any essential limitation recited by the claims.
Applicant argues that Gosh teaches at page 9 that AHDF (fibroblast) numbers increased significantly on the stiffest hydrogels while those on the softest ones underwent a decline suggesting inhibition in cell adhesion or death or both. Applicant asserts that Gosh is both not relevant and teaches away from the claimed invention.
This is not found persuasive. First, Ghosh teach that their data shows that stiff substrates induce strong cellular traction and that tractional force correlates inversely with cell migration speed (page 9, 2nd paragraph). Second, the Mooney reference specifically indicates that their method uses the softer hydrogels (page 24 para 154) and that the cells egress (migration) is to be controlled (page 1 para 6). Third, even if Gosh could be construed as a teaching of a cell decline with regard to the use of softest hydrogels it would be with regard to fibroblasts and not any and all cells contacted with such soft hydrogels as suggested by Mooney.
Applicant argues that Hanjaya-Putra cannot provide the missing teaching of Mooney and Reid because Hanjaya-Putra is limited to methods and compositions for vascularization and point to the abstract and claims as evidence. Applicant argues that the teaching of Hanjaya-Putra can only be used for varying stiffness of hydrogels for varying kinetics of EPC tubulogenesis and cannot be used for the treatment of liver, pancreas or other organ diseases as recited by the present claims.
This is not found persuasive. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Hanjaya-Putra teach the viscoelasticities of hydrogels (including hyaluronic acid) intended for use in regenerative medicine (page 2 para 10, para 17, page 3 para 35) and indicate that values of 650 +/- 180 Pa provide a rigid hydrogel, 75 +/-40 Pa for a firm hydrogel and 10+/-2 Pa for a yielding hydrogel (page 3 para 35). Cell migration is discussed as well (page 7 para 77, page 8 para 87, para 91, page 9 para 92, page 15 para 153, pages 18-19, para 180). The Mooney reference specifically indicates that their method uses the softer hydrogels (page 24 para 154) and that the cells egress (migration) is to be controlled (page 1 para 6). Hanjaya-Putra provides the necessary information regarding hydrogel viscosities required by Mooney in order to optimize the administration of therapeutic cells to damaged target tissue.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See /n re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Hanjaya-Putra et al, “Hydrogel-based Vascular Lineage Cell Growth Media and Uses Thereof”, EP 2504432.
El-Sherbiny et al., “Hydrogel scaffolds for tissue engineering: Progress and challenges”, Global Cardiology Science and Practice, 2013, 2013(3), pp. 316-342.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached on 8:30-5:00 EST.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/ Primary Examiner, Art Unit 1631