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 .
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.
Claim 11 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of copending Application No. 18/567094 in view of Jiang K, et al. 2018.
Claim 11 is to a method of treating diabetes in a subject comprising, culturing islets according to claim 1 wherein claim 1 is a method of culturing islet cells, the method comprising: (a) obtaining islet cells from a donor; and (b) incubating the islet cells in a cell culture medium comprising a hydrogel and a gastrin compound. Claim 11 further claims obtaining the cultured islet cells, then administering them to a subject in an effective amount.
Application No. 18/567094 claim 8 depends from claim 1. Claim 1 is a method of treating diabetes in a subject in need thereof, said method comprising administering a dosage of gastrin-treated human islet cells to said subject. Claim 8 further claims wherein said gastrin-treated human islet cells are obtained by a method comprising: culturing islet cells from a donor; contacting said culture with gastrin. Application No. 18/567094 does not disclose that the gastrin treated cells be cultured with a hydrogel.
Jiang K, et al. 2018 discloses that “The in situ 3-D encapsulation of human or rat islets within ECM hydrogels resulted in improved functional stability over standard culture conditions. Islet composition and morphology were also altered, with enhanced retention of islet-resident endothelial cells and the formation of cord-like structures or sprouts emerging from the islet spheroid.” (abstract).
Jiang K, et al. 2018 details how the use of hydrogels in 3D culture improves islets cell functionality and morphology. Thus, it provides an express teaching, suggestion, and/or motivation to employ the use of a hydrogel in islet cell culture conditions. Therefore, it would be obvious to one of skill in the art before the effective filing date to add a hydrogel during the culture and gastrin treatment of islet cells as outlined in Application No. 18/567094 claim 8.
This is a provisional nonstatutory double patenting rejection.
Claim 12 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 9 of copending Application No. 18/567094 in view of Jiang K, et al. 2018.
Claim 12 depends from claim 11 (addressed above) and adds the step of administering to the subject an effective amount of a gastrin compound.
Application No. 18/567094 claim 9 depends from claim 1. Claim 1 discloses, a method of treating diabetes in a subject in need thereof, said method comprising administering a dosage of gastrin-treated human islet cells to said subject. Claim 9 further comprises administering to said subject gastrin. Application No. 18/567094 claim 9 does not disclose obtaining islet cells from donors or the culture of islet cells in the presence of a hydrogel.
Jiang K, et al. 2018 discloses that “The in situ 3-D encapsulation of human or rat islets within ECM hydrogels resulted in improved functional stability over standard culture conditions. Islet composition and morphology were also altered, with enhanced retention of islet-resident endothelial cells and the formation of cord-like structures or sprouts emerging from the islet spheroid.” (abstract). Application No. 18/567094 claim 8 also discloses obtaining islet cells from a donor.
Jiang K, et al. 2018 details how the use of hydrogels in culture improves islets cell functionality and morphology. Thus, it provides an express teaching, suggestion, and/or motivation to employ the use of a hydrogel in islet cell culture conditions. Therefore, it would be obvious to one of skill in the art before the effective filing date to add a hydrogel during the culture and gastrin treatment of islet cells. Application No. 18/567094 also provides a suggestion to obtain islet cells from a donor. Thus, it would be obvious to one of skill in the art before the effective filing date to obtain islet cells from a donor and culture them in a composition containing a hydrogel.
This is a provisional nonstatutory double patenting rejection.
Claim 13 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-11 of copending Application No. 18/567094.
Claim 13 depends from claim 12 (outlined above) and further claims wherein the gastrin compound is administered pre or post administration of the islet cell transplant.
Claim 10 of Application No. 18/567094 depends from claim 9 (outlined above) and further claims wherein said gastrin is administered to the subject prior to said administration of said dosage of gastrin-treated human islet cells. Claim 11 of Application No. 18/567094 depends from claim 9 (outlined above) and further claims wherein said gastrin is administered to the subject after said administration of said dosage of gastrin-treated human islet cells.
As stated above, claim 12 of the examined application is an obvious variation of claim 9 of Application No. 18/567094 (page 9). Claim 10-11 of Application No. 18/567094 simply claim the addition of gastrin before (claim 10) or after (claim 11) treatment with cultured islets. The same limitations are claimed in claim 13 of the currently examined application, specifically, the gastrin compound is administered pre or post administration of the islet cell transplant
This is a provisional nonstatutory double patenting rejection.
Claim 14 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 13 of copending Application No. 18/567094.
Claim 14 depends from claim 12 (outlined above) and further claims wherein the gastrin compound is administered to the subject once or twice daily for about 30 days.
Claim 13 of copending Application No. 18/567094 depends from claim 9 (outlined above) and further claims wherein said gastrin is administered to said subject at least one time per day for about 30 days.
As stated above, claim 12 of the examined application is an obvious variation of claim 9 of Application No. 18/567094. Claim 14 of the examined application specifies that the gastrin compound be administered once OR twice a day for 30 days. Claim 13 of copending Application No. 18/567094 claims the said gastrin is administered to said subject at least one time per day for about 30 days. Thus claim 13 of copending Application No. 18/567094 overlaps completely with claim 14 of the examined application.
This is a provisional nonstatutory double patenting rejection.
Claim 15 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 of copending Application No. 18/567094 in view of Jiang K, et al. 2018.
Claim 15 depends from claim 12 (outlined above) and further claims wherein the gastrin compound is gastrin-34, gastrin-17, or gastrin-14.
Claim 6 of copending Application No. 18/567094 depends from claim 1. Claim 1 discloses, a method of treating diabetes in a subject in need thereof, said method comprising administering a dosage of gastrin-treated human islet cells to said subject. Claim 6 further claims wherein said gastrin-treated human islet cells are treated with gastrin 17. Application No. 18/567094 claim 6 does not disclose obtaining islet cells from donors or the culture of islet cells in the presence of a hydrogel.
Jiang K, et al. 2018 discloses that “The in situ 3-D encapsulation of human or rat islets within ECM hydrogels resulted in improved functional stability over standard culture conditions. Islet composition and morphology were also altered, with enhanced retention of islet-resident endothelial cells and the formation of cord-like structures or sprouts emerging from the islet spheroid.” (abstract). Application No. 18/567094 claim 8 also discloses obtaining islet cells from a donor.
The rationale for combining the disclose of donor isolated islets (outlined in Application No. 18/567094 claim 8) with the disclosure of culturing islets with a hydrogel (as disclosed by Jiang K, et al. 2018) can be found above. Thus, we know that claim 12 of the examined application (which claim 15 depends from) is obvious in view of claim 1 in copending Application No. 18/567094 (which claim 6 depends from). Claim 15 of the examined application outline the gastrin compound is gastrin-34, gastrin-17, or gastrin-14. Claim 6 of copending Application No. 18/567094 claims wherein said gastrin-treated human islet cells are treated with gastrin 17.
This is a provisional nonstatutory double patenting rejection.
Claim 16 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of copending Application No. 18/567094.
Clam 16 is dependent on claim 12 (outlined above) and further claims administering to the subject about 0.01 microgram to about 100 micrograms of the gastrin compound.
Claim 16 of copending Application No. 18/567094 depends from claim 9 (outlined above) and further claims wherein said gastrin is administered to said subject at a dosage of about 15 μg/kg.
As stated above, claim 12 of the examined application is an obvious variation of claim 9 of Application No. 18/567094. Furthermore, claim 16 of the examined application claims administering to the subject about 0.01 microgram to about 100 micrograms of the gastrin compound, and claim 16 of copending Application No. 18/567094 further claims wherein said gastrin is administered to said subject at a dosage of about 15 μg/kg. In the instance where the subject is a small mouse (approximately 1.5kg) the total dosage of gastrin will be about 23ugs. Therefore, claim 16 of copending Application No. 18/567094 overlaps Claim 16 of the examined application.
Claim 17 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 25 of copending Application No 18/567094 in view of Jiang K, et al. 2018 and Application No. 16/625501.
Claim 17 depends from claim 12 (outlined above) and further claims wherein the diabetes is Type 1 diabetes or Type 2 diabetes.
Claim 25 of copending Application No 18/567094 depends from claim 1. Claim 1 claims method of treating diabetes in a subject in need thereof, said method comprising administering a dosage of gastrin-treated human islet cells to said subject. Claim 25 further claims wherein said subject has Type 1 diabetes. Claim 25 does not disclose obtaining islet cells from donors or the culture of islet cells in the presence of a hydrogel.
The rationale for combining the disclose of donor isolated islets (outlined in application No 18/567094 claim 8) with the disclosure of culturing islets with a hydrogel (as disclosed by Jiang K, et al. 2018) can be found above. This renders claim 1 of copending Application No 18/567094 obvious over claim 12 of the examined application. Claim 25 of copending Application No 18/567094 (which depends from claim 1) further claims wherein said subject has Type 1 diabetes and claim 17 of the examined application (which depends from claim 12) further claims wherein the diabetes is Type 1 diabetes or Type 2 diabetes. Thus, Claim 25 of copending Application No 18/567094 overlaps with claim 17.
This is a provisional nonstatutory double patenting rejection.
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.
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 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.
Claims 1-4, 8-17 are rejected under 35 U.S.C. 103 as being unpatentable over PG PUB US 20040037818 A1 filed 05/27/2003, and further in view of Jiang K, et al. 2018 and US 7803766 B2.
Claim 1 claims a method of culturing islet cells comprising: (a) obtaining islet cells from a donor; and (b) incubating the islet cells in a cell culture medium comprising a hydrogel and a gastrin compound. Claim 2 further claims the gastrin compound is gastrin-34, gastrin-17, or gastrin-14. Claim 3 further claims the sequences of gastrin in claim 2 are SEQ ID1-4. Claim 4 further claims that the concentration of gastrin is about 100 nM to about 600 nM. Claim 8 further claims that the incubation is for more than three days. Claim 9 further claims incubating is for at least a week, at least two weeks, at least three weeks, or at least four weeks. Claim 10 further claims incubating is for about two weeks to about four weeks.
Claim 11 claims a method of treating diabetes in a subject in need thereof, the method comprising: (a) culturing islet cells according to claim 1, thereby obtaining cultured islet cells; and (b) administering to the subject an effective amount of the cultured islet cells. Claim 12 further claims administering to the subject an effective amount of a gastrin compound. Claim 13 claims the gastrin compound of claim 12 is administered pre or post administration of the islet cell transplant. Claim 14 claims the gastrin compound of claim 12 is administered to the subject once or twice daily for about 30 days. Claim 15 claims the gastrin compound of claim 12 is gastrin-34, gastrin-17, or gastrin-14. Claim 16 claims administering to the subject about 0.01 microgram to about 100 micrograms of the gastrin compound from claim 12. Claim 17 claims the diabetes from claim 11 is Type 1 diabetes or Type 2 diabetes.
In an exemplary embodiment (example 11) PG PUB US 20040037818 A1 discloses, “Islet cell preparations were isolated from human donor pancreases…Islet cells were seeded… and cultured for 4 weeks, in serum free-MEM medium alone or supplemented with EGF (0.3 .mu.g/ml), gastrin (1.0 .mu.g/ml), or EGF+gastrin in combination for 4 weeks and maintained in culture for an additional 4 weeks.” (paragraph 0129). It does not disclose that the gastrin used in culture be gastrin-34, gastrin-17, or gastrin-14. It does not disclose the sequences of SEQ ID1-4. The embodiment does not disclose the use of a hydrogel during islet cell culture or using the cells from the culture to treat diabetes. It does not disclose the administration of gastrin to a subject before or after the administration of the islet cell culture. It does not disclose administering the gastrin treatment once or twice daily for about 30 days. It does not disclose the use of is gastrin-34, gastrin-17, or gastrin-14 as the specific type of gastrin that is administered to the subject in claim 12, or that the total amount of gastrin administered is about 0.01 to 100 ug. It also does not disclose that the diabetes treated in claim 11 be Type 1 diabetes or Type 2 diabetes.
PG PUB US 20040037818 A1 does disclose, “Examples of such gastrin/CCK receptor ligands include various forms of gastrin such as gastrin 34 (big gastrin), gastrin 17 (little gastrin)…” (paragraph 0030). The combination of these disclosures outlines all the elements of claim 1 (islets isolated from donor, cultured in gastrin see paragraph 0129) except for a hydrogel. It outlines that the gastrin compound used in culture can be gastrin 34 or gastrin 17 (claim 2 see paragraph 0030). Upon unit conversion, we find that 1.0ug/ml of gastrin 34 is equivalent to 258nM of gastrin 34 (claim 4 see paragraph 0129). US 7803766 B2 discloses the use of SEQ IDs 1-4 (“description section, paragraph 24 and 25) for use in treating diabetes (claim 3). The disclosure also instructs gastrin treatment in culture occur for 4 weeks, which is more than 3 days (claim 8 see paragraph 0129), at least a week (claim 9 see paragraph 0129), and between 2 and 4 weeks (claim 10 see paragraph 0129).
PG PUB US 20040037818 A1 also discloses, “Methods of transplantation include transplanting insulin secreting pancreatic .beta.-cells obtained into a patient in need thereof…”(paragraph 0059), and, “The transplant recipient can also, according to the invention, be provided with a sufficient amount of a gastrin/CCK receptor ligand and an EGF receptor ligand to induce proliferation of the transplanted insulin secreting .beta. cells.” (paragraph 0059). Exemplary embodiment 8, namely, “Characterization of Human Islet Grafts Transplanted to Mice and Treated in vivo with a Gastrin and an EGF” (paragraph 0111), states that “Mice were transplanted with human islets (2000 islet equivalent) under the kidney capsule… (paragraph 0112) (claim 11). This embodiment also details the effects of in-vivo gastrin treatment of the human islet grafts (paragraph 0114, claims 12-13). Furthermore they state that, “Examples of such gastrin/CCK receptor ligands include various forms of gastrin such as gastrin 34 (big gastrin), gastrin 17 (little gastrin)…” (paragraph 0030) (claim 15).
Furthermore, US 20040037818 A1 discloses, “However, suitable dosage ranges for intravenous administration are generally about… 0.1 to 5000 micrograms of active compound per kilogram body weight for a gastrin receptor ligand.” (paragraph 0051). Assuming a mouse weighs 1.5kg and 1.0ug/kg of gastrin is used as the treatment regimen, the total amount of gastrin administered would be 1.5ug of gastrin a day. PG PUB US 20040037818 A1 also discloses exemplary embodiment 5, namely, “Dose-Dependent Effects of in vivo Treatment with Gastrin on Fasting Blood Glucose in NOD Mice with Chronic Insulin-Dependent Diabetes” (paragraph 102). Insulin-Dependent Diabetes is another name for type I diabetes. “NOD mice with chronic insulin-dependent diabetes and maintained on insulin therapy were distributed into different treatment groups treated with: (i) vehicle (n=4); (ii) G1 1 .mu.g/kg/day, given i.p. twice daily (n=4) for 28 days…” (paragraph 0103). Thus, treatment regime of 1ug/kg/day given twice daily for 28 days (claim 14) results in total gastrin treatment of 84ug in 1.5kg mouse (claim 16) in Insulin-Dependent Diabetes/ type I diabetes mice (claim 17) (exemplary embodiment 5, paragraph 0102-0104).
Jiang K, et al. 2018 discloses that “The in situ 3-D encapsulation of human or rat islets within ECM hydrogels resulted in improved functional stability over standard culture conditions. Islet composition and morphology were also altered, with enhanced retention of islet-resident endothelial cells and the formation of cord-like structures or sprouts emerging from the islet spheroid.” (abstract).
Jiang K, et al. 2018 details how the use of hydrogels in culture improves islets cell functionality and morphology. Thus, it provides an express teaching, suggestion, and/or motivation to employ the use of a hydrogel in islet cell culture conditions. Therefore, it would be obvious to one of skill in the art before the effective filing date to add a hydrogel during the culture and gastrin treatment of islet cells. This renders claim 1 obvious. PG PUB US 20040037818 A1 also provides several teachings/suggestions, and/or motivations in their disclosure that render claims 11-17 obvious. It has been established that it would be obvious to include a hydrogel in the culture of isolated human islet cells (as stated above, see Jiang K. et al. 2018). It is outlined in the disclosure that 0.1 to 5000ug of gastrin receptor ligand per kilogram of body weight is suitable. It is also outlined that the gastrin receptor ligand can be either gastrin 34 (big gastrin) or gastrin 17 (little gastrin). The result of implanting mice with isolated human islets (previously maintained in culture) and further treating the subjects with 1.5ug of either gastrin 34 or gastrin 17 has therapeutic benefit. For instance, “Treatment with gastrin/EGF induced increases in insulin-positive .beta.-cells in human islets implanted…”(paragraph 0116), and “In FIG. 11, the upper panels (data from cells from an intact islet graft) show that insulin-staining .beta.-cells were more abundant in a human islet graft from a mouse administered gastrin/EGF therapy, than from a mouse administered vehicle.” (paragraph 0116). The increase in the number insulin-positive .beta.-cells in human islet cells has significant benefits for patients suffering from Type I diabetes. These embodiments and disclosures provide a strong teaching/motivation and/or suggestion to a person skilled in the art, before the effective filing date, to implant isolated islet cells that have been cultured in the presence of a hydrogel and gastrin into a diabetic subject and to then treat the subject with 1.5ug of gastrin 35 or gastrin 17 after implantation to improve therapeutic outcomes. Thus, these disclosures render claims 11-13 and claims 15-16 obvious. It shows that “there was a corresponding decrease of fasting blood glucose levels with increasing dose of G1 (5 and 10 .mu.g/kg/day, respectively). See FIG. 4. These data show that treatment with gastrin significantly improves glucose control, without the use of insulin therapy, in chronically diabetic insulin-dependent NOD mice.” (paragraph 104). These results provide strong teaching/motivation and/or suggestion to a person skilled in the art, before the effective filing date, to administer 1.5ug/day two times a day of gastrin 35 or gastrin 17 for 28 days (total of 84ug gastrin) to a subject suffering from type I diabetes.
Furthermore, it would be obvious to a person skilled in the art, before the effective filling date, to combine both embodiments above because it is the equivalent of combining known elements to achieve predictable results. As stated above, it is known that the result of implanting in mice isolated human islets (previously maintained in culture) and further treating the subjects with 1.5ug of either gastrin 34 or gastrin 17 has therapeutic benefit. It also is known that the administration of 1.5ug/day two times a day of gastrin 35 or gastrin 17 for 28 days (total of 84ug gastrin) to a subject suffering from type I diabetes also results in therapeutic benefit. Thus, it would be expected that the result of implanting isolated human islets (previously maintained in culture) in mice suffering from type I diabetes, and further treating the subjects with 1.5ug/day twice a day of gastrin 34 or gastrin 17 for 28 days would result in an additive therapeutic effect. Thus, claim 14 and 17 are rendered obvious.
Claims 1-2, 4-6, and 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over PG PUB US 20040037818 A1 filed 05/27/2003 and Jiang K, et al. 2018, as applied to claim 1 and further in view of Noguchi H, et al. 2006, and as evidenced by Yuhei Mizunoe, et al. 2018.
Claim 1 claims a method of culturing islet cells comprising: (a) obtaining islet cells from a donor; and (b) incubating the islet cells in a cell culture medium comprising a hydrogel and a gastrin compound. Claim 5 further claims the cell culture medium further comprises trehalose. Claim 6 further claims that the concentration of trehalose is between about 0.01 M to about 0.35 M.
Claim 1 is rendered obvious over the prior art PUB US 20040037818 A1 filed 05/27/2003 and Jiang K, et al. 2018 as rationalized above. PUB US 20040037818 A1 and Jiang K, et al. 2018 do not disclose the use of trehalose in the culture medium, and furthermore they do not disclose the use of trehalose in a concentration of about 0.01M to about 0.35 M.
Noguchi H, et al. 2006 discloses, “In this study, we investigated the features of a new solution, designated M-Kyoto solution. M-Kyoto solution contains trehalose and ulinastatin as distinct components. Trehalose has a cytoprotective effect against stress, and ulinastatin inhibits trypsin. In porcine islet isolation, islet yield was significantly higher in the M-Kyoto/PFC group compared with the UW/PFC group.” (abstract). The solution compositions can be found in Table 1. Note that the M-Kyoto solution contains 120mm/L trehalose, which is equal to 0.120 M. Furthermore, “Islet yield both before and after purification was significantly higher in the M-Kyoto/PFC group (n = 5) compared with the UW/PFC group (n = 5) (before purification: MKyoto/PFC; 6946 ± 583 IE/g, UW/PFC; 4395 ± 387 IE/g, after purification: M-Kyoto/PFC; 3936 ± 566 IE/g, UW/PFC; 2885 ± 290 IE/g) (Figure 1). (“Results” section, 2nd paragraph).
Noguchi H, et al. 2006 shows that including trehalose in solution during the isolation of islets from a donor improves islet yields before and after purification. Their findings combined with the fact that trehalose is known cytoprotective agent (as evidenced by Yuhei Mizunoe. et al. 2018) provides a clear teaching and motivation to combine trehalose in the medium used to culture islet cells after they have been isolated from a donor, as claim 5 states. Thus, it would have been obvious to one of skill in the art before the effective filling date to include trehalose (claim 5), and in particular trehalose at a concentration of 0.120M (claim 6), in the culture medium of islets cells after they have been isolated from a donor. Thus, claim 5 and 6 are rendered obvious.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over PG PUB US 20240261475 A1 filed 05/26/2022 (priority date 05/31/2021) further in view of PG PUB US 20040037818 A1 and Jiang K, et al. 2018.
Claim 1 is rendered obvious as stated above (page 16). Claim 7 further claims that the hydrogel comprises a soft polysaccharide hydrogel capable of conversion to a hard polysaccharide hydrogel, the soft polysaccharide hydrogel comprising: (a) one or more water soluble high acyl gellan gum polymers; (b) one or more water soluble low acyl gellan gum polymers; and (c) one or more water soluble chemically modified gellan gum polymers or one or more peptide modified gellan gum polymers, wherein the soft polysaccharide hydrogel exhibits a homogeneous matrix structure and the hard polysaccharide hydrogel exhibits an aggregated matrix network structure.
PG PUB US 20040037818 A1 and Jiang K, et al. 2018 disclose obtaining islet cells from a donor; and (b) incubating the islet cells in a cell culture medium comprising a hydrogel and a gastrin compound (aka claim 1). They do not disclose that the hydrogel comprises a soft polysaccharide hydrogel capable of conversion to a hard polysaccharide hydrogel, the soft polysaccharide hydrogel comprising: (a) one or more water soluble high acyl gellan gum polymers; (b) one or more water soluble low acyl gellan gum polymers; and (c) one or more water soluble chemically modified gellan gum polymers or one or more peptide modified gellan gum polymers, wherein the soft polysaccharide hydrogel exhibits a homogeneous matrix structure and the hard polysaccharide hydrogel exhibits an aggregated matrix network structure.
PG PUB US 20240261475 A1 discloses, “The present invention relates to a method for preparing cell-laden collagen-gellan gum interpenetrating network (IPN) hydrogel using 3D-bioprinter and a 3D printed hydrogel obtainable from said method…” (paragraph 0001). “’Bioink’ is defined as cell compatible material that can be 3D printed and provides a support to cells or comprises cells.” (paragraph 0032). “In one embodiment, the present disclosure relates to a first bioink comprising gellan gum…” (paragraph 0033). Furthermore, “Gellan gum includes, but is not limited to, low-acyl gellan gum, high-acyl gellan gum, chemically modified gellan gum, or any mixture of these gellan gum polymers.” (paragraph 0034). They go on to find that, “The cell viability of 3D-bioprinted ADSC was determined to be 77.4% of the cell viability of ADSC encapsulated within manually fabricated hydrogel films (FIG. 5).” and “no drastic reduction in cell viability of 3D-bioprinted ADSC was observed, the present 3D-printing methodology is adequately designed for fabricating the ADSC-laden gellan gum-collagen IPN hydrogel films.” (paragraph 0109). The finding that there was no drastic reduction in cell viability when using gellan gum polymers during the printing of 3D hydrogel networks embedded with cells provides a strong teaching/motivation to combine the use of gellan gum compositions, including ones containing low-acyl gellan gum, high-acyl gellan gum and chemically modified gellan gum, in the 3D culture of cells for therapeutic applications. Thus, it would have been obvious to a person of skill in the art to use a hydrogel comprising one or more water soluble high acyl gellan gum polymers; (b) one or more water soluble low acyl gellan gum polymers; and (c) one or more water soluble chemically modified gellan gum polymers as their scaffold in the 3D culture of islet cells. This renders claim 7 obvious.
Claims 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over PG PUB US 20040037818 A1 as applied to claims 18-20 above, and further in view of Jiang K, et al. 2018.
Claim 18 is to an islet cell culture comprising islet cells, a hydrogel, a gastrin compound, and a culture medium, and claim 19 is to a cell obtained by the method of claim 1. Claim 20 is to a kit for culturing islet cells comprising a hydrogel and a gastrin compound.
In an exemplary embodiment (embodiment 11) PG PUB US 20040037818 A1 discloses, “Islet cell preparations were isolated from human donor pancreases…Islet cells were seeded… and cultured for 4 weeks in serum free-MEM medium alone or supplemented with EGF (0.3 .mu.g/ml), gastrin (1.0 .mu.g/ml)…”(paragraph 0129). The embodiment does not disclose the use of a hydrogel during islet cell culture.
Jiang K, et al. 2018 discloses that “The in situ 3-D encapsulation of human or rat islets within ECM hydrogels resulted in improved functional stability over standard culture conditions. Islet composition and morphology were also altered, with enhanced retention of islet-resident endothelial cells and the formation of cord-like structures or sprouts emerging from the islet spheroid.” (abstract).
Jiang K, et al. 2018 details how the use of hydrogels in culture improves islets cell functionality and morphology. Thus, it provides an express teaching, suggestion, and/or motivation to employ the use of a hydrogel in islet cell culture conditions. Therefore, it would be obvious to one of skill in the art before the effective filing date to add a hydrogel during the culture and gastrin treatment of islet cells. This would result in a culture comprising an islet cell, gastrin, a hydrogel, and a culture medium, and render claim 18 obvious. Also, where the claimed composition is the direct and inevitable result of an obvious method, the composition itself is rendered obvious. See In re Best, 562 F.2d 1252 (CCPA 1977).
Claim 19, a product by process claim, is unpatentable because the claimed cell culture is not patentably distinct from the cell cultures disclosed in Jiang K, et al. 2018 and PG PUB US 20040037818 A1. The references teach the same combination of cells, media, gastrin and hydrogel.
For claim 20 the MPEP states, “where the printed matter and product do not depend upon each other, no functional relationship exists. For example, in a kit containing a set of chemicals and a printed set of instructions for using the chemicals, the instructions are not related to that particular set of chemicals. See In re Ngai, 367 F.3d at 1339, 70 USPQ2d at 1864.” (MPEP 2111.05 I). Claim 20 amounts to nonfunctional descriptive material. A kit containing the obvious combination of gastrin and a hydrogel, is not rendered patentable by the mere addition of instructions on how to perform the culture method. There is no new and unobvious functional relationship between the printed matter and the substrates as claimed.
Conclusion
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/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638