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 .
Applicant is requested to note that the Examiner for this application has changed.Future correspondence should be directed to Laura Schuberg, Art Unit 1631, whosecontact information can be found below.
Election/Restrictions
Applicant's election with traverse of Group I (claims 26-47) and species treating liver in the reply filed on 12/01/2025 is acknowledged. The traversal is on the ground(s) that there would be no serious burden to examine all the claims and all the species together.
This is not found persuasive because, as shown in the restriction requirement, the two different inventive groups are directed each to distinct subject matter; a reference which would anticipate or render obvious claims of one group would not necessarily anticipate or render obvious claims of another group. The different inventions each had different classifications, which is demonstrative of the divergent searches which would need to be conducted for each invention. Additionally, a thorough search of all non-patent literature related to each of the distinct groups would, in fact, pose a serious burden on the examiner.
The species election requirements have been withdrawn because the species have shown themselves to be art -recognized equivalents. However, the group restriction requirements remain.
The requirement is still deemed proper and is therefore made FINAL.
Claim 48 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 06/04/2025.
Claims 26-47 have been examined on their merits.
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.
Claim 37 is 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.
Claim 37 recites the phrase “wherein said epithelial cells comprise biliary tree stem cells (BTSCs), hepatocytes, cholangiocytes, islet cells, and combinations thereof”. This renders the scope of the claim unclear as to whether all or just one of the cell types are required by the claim.
For examination purposes the claim is interpreted as requiring at least one of the cell types or combinations thereof.
Appropriate correction is required.
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.
Claims 26-43 and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Mooney et al (US 2008/0044900-from IDS filed 07/18/2022) in view of Turner et al (US 2011/0274666-from IDS filed 07/18/2022).
Regarding claims 26-28, 40 and 47, Mooney teach a cell transplantation device that contains a mixture of cells and can be used for liver 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) and liver 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 (migration) 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). Mooney teach that alternatively, or in addition, egress (migration) is regulated by a bioactive composition that controls and directs the migration of cells through its structure to attract or retard the migration of cells (page 1 para 7). This would render obvious a material that would inhibit cell migration towards an undesired direction, away from the target tissue and towards the backing material.
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 stemness and prevent differentiation) (page 10 para 68-69). 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 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. Mooney include wherein their polymeric carriers include a mesh (pages 12-13 para 79) and specifically wherein the scaffold (backing) 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).
Mooney specifically teach wherein their transplantation systems enhance viability of the cells and induce outward migration to populate injured or defective tissues (promote cell growth and proliferation) to enhance the success of tissue regeneration (page 1 para 4). Mooney also discloses the encapsulation of cells in compartments/layers of their devices with factors that promote the stem cells to rapidly proliferate and generate large numbers of cells (page 10 para 68-69).
One of ordinary skill in the art would have been motivated to select liver tissue injured by diseases such as hepatitis because Turner suggest that such injured tissue is in need of repair and would benefit from a mixture of hepatocytes, stem and progenitor cells (page 5 para 52-53). One of ordinary skill in the art would have had a reasonable expectation of success in applying the method of Mooney to liver tissue injured by hepatitis because Mooney suggests that damaged liver tissue is a suitable tissue type for their method and Mooney also includes the use of a mixture of stem, progenitor and liver cells in their composition as well.
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).
Regarding claim 29, further comprising step c, 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 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 as described above, the addition of a hydrogel layer on the opposite side of the backing away from the cells (a third hydrogel layer) would be obvious to reinforce the backing of the scaffold and prevent the egress of cells away from the target tissue. Selecting a viscosity for such a third hydrogel layer that promotes the desired effect and thus minimizes adhesions from neighboring tissues would be a matter of routine optimization and experimentation as the viscosity that provides this effect (250 to 500 Pa as per claim 30) is within the range disclosed by the prior art references cited above One of ordinary skill in the art would have had additional motivation and a reasonable expectation of success because Mooney specifically suggests adding layers to regulate cell locomotion (migration) (page 3 para 18) and outer coverings (page 24 para 154).
Regarding claims 30-32, Mooney suggests wherein the hydrogels are made from hyaluronic acid (hyaluronan) (page 8 para 51-52).
Regarding claim 33, Mooney teach wherein the cells may include a hydrogel medium that contains factors required to maintain the multipotent nature of stem cells (maintain stemness) (page 10 para 68-69).
Regarding claims 34-37, Mooney teach wherein the mixed cells may include adult stem cells, mesenchymal stem cells (MSCs, early lineage stage mesenchymal cell, ELSMCs), hepatocytes, epithelial cells (page 3 para 17 and page 6 para 44).
Regarding claim 38, Mooney teach wherein the cells are autologous or allogeneic (page 14 para 92).
Regarding claim 39, Mooney teach wherein the cells are programmed/reprogrammed (genetically modified) (page 15 para 97).
Regarding claims 41-42, 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 43, 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).
The combined teachings of Mooney et al and Turner et al render obvious Applicant's invention as claimed.
Claim(s) 44-46 are rejected under 35 U.S.C. 103 as being unpatentable over Mooney et al (US 2008/0044900-from IDS filed 07/18/2022) in view of Turner et al (US 2011/0274666-from IDS filed 07/18/2022) as applied to claims 26-43 and 47 above, and further in view of Ghosh et al (Biomaterials, 2007-from IDS filed 07/18/2022) and Hanjaya-Putra et al (US 2012/0225814-from IDS filed 07/18/2022).
Regarding claims 44-46, 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 have been 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.
The combined teachings of Mooney et al, Turner et al, Ghosh et al and Hanjaya-Putra et al render obvious Applicant's invention as claimed.
Claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over Mooney et al (US 2008/0044900-from IDS filed 07/18/2022) in view of Turner et al (US 2011/0274666-from IDS filed 07/18/2022) as applied to claims 26-43 and 47 above, and further in view of Carpino et al (Journal of Anatomy 2012-from IDS filed 07/18/2022).
Regarding claim 37, the combined teachings of Mooney et al and Turner et al render obvious Applicant's invention as described above and Mooney teach wherein the mixed cells may include adult stem cells, mesenchymal stem cells (MSCs, early lineage stage cell), hepatocytes, epithelial cells (page 3 para 17 and page 6 para 44), but are silent with regard to the inclusion of biliary tree stem cells (BTSCs).
Carpino teaches BTSCs and characterization of said cells (abstract). Carpino teach that biliary tree stem/progenitors (BTSCs) are multipotent, giving rise in vitro and in vivo to hepatocytes (abstract). Carpino teach that BTSCs are likely to be central to normal tissue turnover and injury repair and useful in cell therapy programs for the liver (abstract, page 197, column 2).
Therefore, one of ordinary skill in the art would have been motivated to include BTSCs in the patch graft method of Mooney because Carpino teach that BTSCs are involved in normal tissue turnover and injury repair, and thus would be effective for patch graft use in hepatic tissues. One of ordinary skill in the art would have had a reasonable expectation of success because Mooney also indicates that adult stem cells, such as MSCs (early lineage stage mesenchymal cells-ELSMCs) are suitable for inclusion in their method and specifically include the liver as a site for repair of damaged tissue as described above.
Therefore, the combined teachings of Mooney et al, Turner et al, and Carpino 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 26-47 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,129,923 in view of Mooney et al (US 2008/0044900-from IDS filed 07/18/2022), Turner et al (US 2011/0274666-from IDS filed 07/18/2022), Carpino et al (Journal of Anatomy 2012-from IDS filed 07/18/2022) and Ghosh et al (Biomaterials, 2007- from IDS filed 07/18/2022) and Hanjaya-Putra et al (US 2012/0225814- from IDS filed 07/18/2022).
The claims of the patent are drawn to patch graft compositions.
The patented claims do not specifically include wherein the target tissue is liver tissue, a specific liver disease and wherein the cells include liver cells such as hepatocytes and biliary tree stem cells.
Mooney, Turner, Carpino, Ghosh et al and Hanjaya-Putra et al render obvious liver tissue as a target tissue for a patch graft and suggest the inclusion of hepatocytes and biliary tree stem cells as well as the claimed viscoelasticities described above.
Therefore, the combined teachings Mooney et al, Turner et al, Carpino et al, Ghosh et al, Hanjaya-Putra et al and the patented claims render obvious Applicant's invention as claimed.
Claim 26-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10-11, 15-18, 21, 28-29, 32-33, 39-43 of copending Application No. 16/006,460 (reference application) in view of Mooney et al (US 2008/0044900-from IDS filed 07/18/2022), Turner et al (US 2011/0274666-from IDS filed 07/18/2022), Carpino et al (Journal of Anatomy 2012-from IDS filed 07/18/2022) and Ghosh et al (Biomaterials, 2007- from IDS filed 07/18/2022) and Hanjaya-Putra et al (US 2012/0225814- from IDS filed 07/18/2022).
The claims of the copending application are drawn to methods of engrafting cells into a target tissue by contacting the target tissue with a patch graft.
The copending claims do not specifically include wherein the target tissue is liver tissue, a specific liver disease and wherein the cells include liver cells such as hepatocytes and biliary tree stem cells.
Mooney, Turner, Carpino, Ghosh et al and Hanjaya-Putra et al render obvious liver tissue as a target tissue for a patch graft and suggest the inclusion of hepatocytes and biliary tree stem cells as well as the claimed viscoelasticities described above.
Therefore, the combined teachings Mooney et al, Turner et al, Carpino et al, Ghosh et al, Hanjaya-Putra et al and the copending claims render obvious Applicant's invention as claimed.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 26-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 9, 12, 19-20, 23-24, 27 and 29 of copending Application No. 16/006,482 (reference application, allowed but not yet issued).
The claims of the copending application are drawn to methods of treating a subject with a liver disease by contacting the subject’s liver with a patch graft.
The copending claims include wherein the target tissue is liver tissue, a specific liver disease and wherein the cells include liver cells such as hepatocytes and biliary tree stem cells and anticipate the current claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not yet been patented.
Claim 26-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32-33, 35-51, 53-60, 89-94 of copending Application No. 16/422,086 (reference application) in view of Mooney et al (US 2008/0044900-from IDS filed 07/18/2022), Turner et al (US 2011/0274666-from IDS filed 07/18/2022), Carpino et al (Journal of Anatomy 2012-from IDS filed 07/18/2022) and Ghosh et al (Biomaterials, 2007- from IDS filed 07/18/2022) and Hanjaya-Putra et al (US 2012/0225814- from IDS filed 07/18/2022).
The claims of the copending application are drawn to methods of engrafting cells into a solid organ with patch graft compositions.
The copending claims do not specifically include wherein the target tissue is liver tissue, a specific liver disease and wherein the cells include liver cells such as hepatocytes and biliary tree stem cells.
Mooney, Turner, Carpino, Ghosh et al and Hanjaya-Putra et al render obvious liver tissue as a target tissue for a patch graft and suggest the inclusion of hepatocytes and biliary tree stem cells as well as the claimed viscoelasticities described above.
Therefore, the combined teachings Mooney et al, Turner et al, Carpino et al, Ghosh et al, Hanjaya-Putra et al and the copending claims render obvious Applicant's invention as claimed.
This is a provisional nonstatutory double patenting rejection.
Claim 26-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26-48 of copending Application No. 18/239,036 (reference application) in view of Mooney et al (US 2008/0044900-from IDS filed 07/18/2022), Turner et al (US 2011/0274666-from IDS filed 07/18/2022), Carpino et al (Journal of Anatomy 2012-from IDS filed 07/18/2022) and Ghosh et al (Biomaterials, 2007- from IDS filed 07/18/2022) and Hanjaya-Putra et al (US 2012/0225814- from IDS filed 07/18/2022).
The claims of the copending application are drawn to methods of treating a subject with a liver disease or disorder comprising contacting the subject's liver with a patch graft comprising a mixed population having two or more cell types in a first hydrogel having viscoelasticity sufficient to allow for migration of the cells towards the subjects liver and a backing comprising a biocompatible material having a viscoelasticity sufficient to inhibit a migration of the mixed cell population in a direction away from the target tissue and allowing the cells contained in the patch graft to become incorporated into the liver thereby restoring some liver function.
The copending claims do not specifically include the all the limitations in the same claimed combinations, however Mooney, Turner, Carpino, Ghosh et al and Hanjaya-Putra et al render obvious those combinations as described above.
Therefore, the combined teachings Mooney et al, Turner et al, Carpino et al, Ghosh et al, Hanjaya-Putra et al and the copending claims render obvious Applicant's invention as claimed.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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 8:30-5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Doug) Schultz can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631