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 . 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.
Election/Restrictions
Applicant’s election without traverse of SEQ ID 3 in nicotinamide (50-1000 mM) and histidine (1-100 mM) in the reply filed on 14 April, 2025 is acknowledged.
Applicants have elected a formulation of SEQ ID 3 with nicotinamide and histidine. A search was conducted for this invention, and references rendering it obvious were found. As a result, claims 1, 3, 4, 10, and 12-14 were examined and claims 2, 5-9, 11, and 15-19 were withdrawn from consideration. While applicants have stated that they believe their election reads on the withdrawn claims, those claims include unelected excipients, a concentration range different than elected, or some other feature not found in applicant’s elected formulation. Thus, they are properly withdrawn.
Claims Status
Claims 1-19 are pending.
Claims 2, 5-9, 11, and 15-19 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 14 April, 2025.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3, 4, 10, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Tsao et al (US 20120215097) in view of Esfahani et al (Trauma Mon. (2015) 20(4) e18193) and the MadSci network message board, question of 15 April, 2022.
Tsao et al discuss PEDF-derived polypeptides for wound healing (title). A polypeptide of SEQ ID 3, identical with SEQ ID 3 of the examined claims, has corneal and epithelial wound healing ability (paragraph 58). The pH of the formulation is preferably between 4.5 and 8, and maintained there with an appropriate buffer system (paragraph 71). An experiment using this sequence showed improved healing in mice compared to controls (paragraph 115). While the example is vague in how the material is administered, topical administration is mentioned elsewhere (paragraph 20).
The difference between this reference and the examined claims is that this reference does not discuss the claimed formulation.
Esfahani et al discuss nicotinamide in the context of wound healing (title). This drug has anti-inflammatory and antioxidant properties, and regulates the effects of immunomodulatory proteins (1st page, 1st column, 1st paragraph). Formulations used a 2% gel (1st pate, 2nd column, 2nd paragraph). Note that this is 164 mM nicotinamide (20g/L/122 g/mole). This formulation remarkably improved the closure rate of wounds, and is suggested as a beneficial agent or adjuvant therapy for wound healing (6th page, 1st column, 1st paragraph). This reference teaches nicotinamide is also useful in would therapy.
The MadSci network answers a question about histidine buffers (title). The pKa of histidine is 6.0; this is the only amino acid that buffers at physiological pH (3d paragraph). Note that this is within the same pH range as discussed by Tsao et al.
Therefore, it would be obvious to use the histidine buffer of the MadSci network to buffer the formulations of Tsao et al. As this buffer buffers in the same range as described as optimum by Tsao et al, an artisan in this field would attempt this modification with a reasonable expectation of success.
Tsao et al discusses polypeptides of SEQ ID 3 for wound healing. Esfahani et al teaches 164 mM nicotinamide is also useful for wound healing. The MPEP states that it is obvious to combine two compositions each of which are taught by the prior art as useful for the same purpose, in order to form a third composition to be used for the same purpose (MPEP 2144.06(I)). The MadSci network renders obvious using a histidine buffer. While the reference does not discuss the concentration, this is not considered a patentable distinction, as concentrations are routinely optimized (MPEP 2144.05(II)(A)). Note that Esfahani et al state that nicotinamide is an antioxidant. Thus, the combination of references renders obvious claims 1, 3, 4, 10, and 12-14.
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.
first rejection
Claims 1, 3, 4, 10, and 12-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4, 5, and 9 of copending Application No. 18/875,114 in view of Esfahani et al (Trauma Mon. (2015) 20(4) e18193) and Izutsu (in Therapeutic Proteins (2005) ISBN 1-58829-390-4).
Competing claim 4 describes treating dry eye by administering a Markush group of sequences, which competing claim 5 reduces to SEQ ID 3, identical with SEQ ID 3 of the examined claims. Competing claim 9 specifies that the patient has had cataract surgery.
The difference between the competing claims and the examined claims is that the competing claims do not describe the formulation used.
Esfahani et al discuss nicotinamide in the context of wound healing (title). This drug has anti-inflammatory and antioxidant properties, and regulates the effects of immunomodulatory proteins (1st page, 1st column, 1st paragraph). Formulations used a 2% gel (1st pate, 2nd column, 2nd paragraph). Note that this is 164 mM nicotinamide (20g/L/122 g/mole). This formulation remarkably improved the closure rate of wounds, and is suggested as a beneficial agent or adjuvant therapy for wound healing (6th page, 1st column, 1st paragraph). This reference teaches nicotinamide is also useful in would therapy.
Izutsu describes stabilization of therapeutic proteins (title). The first step is to obtain a stability profile in aqueous solutions of different pH and ionic strength, then identify the excipients that affect protein stability (p289 “preformulation studies”). Then, the potential formulations are stress tested (p289, “formulation design”). Note that histidine is explicitly discussed as a buffer, with a typical concentration of 10-50 mM (table 2, p288).
Therefore, it would be obvious to add the nicotinamide to the formulation of the competing claims, as that material assists in wound healing. Note that the MPEP states that it is obvious to combine two compositions each of which are taught by the prior art as useful for the same purpose, in order to form a third composition to be used for the same purpose (MPEP 2144.06(I)).
Furthermore, it would be obvious to attempt histidine buffer in the stability studies, as Izutsu explicitly suggests that buffer. As there are only a few pharmacologically acceptable buffers appropriate for any given pH, an artisan in this field would attempt this formulation with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
second rejection
Claims 1, 3, 4, 10, and 12-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of copending Application No. 18/878,908 in view of Esfahani et al (Trauma Mon. (2015) 20(4) e18193) and Izutsu (in Therapeutic Proteins (2005) ISBN 1-58829-390-4).
Competing claim1 describes a method of treating neurotrophic keratitis, a disease that damages the cornea, using a Markush group of sequences, which competing claim 2 narrows to SEQ ID 3 (identical with SEQ ID 3 of the examined claims.
The difference between the competing claims and the examined claims is that the competing claims do not describe the formulation used.
Esfahani et al discuss nicotinamide in the context of wound healing (title). This drug has anti-inflammatory and antioxidant properties, and regulates the effects of immunomodulatory proteins (1st page, 1st column, 1st paragraph). Formulations used a 2% gel (1st pate, 2nd column, 2nd paragraph). Note that this is 164 mM nicotinamide (20g/L/122 g/mole). This formulation remarkably improved the closure rate of wounds, and is suggested as a beneficial agent or adjuvant therapy for wound healing (6th page, 1st column, 1st paragraph). This reference teaches nicotinamide is also useful in would therapy.
Izutsu describes stabilization of therapeutic proteins (title). The first step is to obtain a stability profile in aqueous solutions of different pH and ionic strength, then identify the excipients that affect protein stability (p289 “preformulation studies”). Then, the potential formulations are stress tested (p289, “formulation design”). Note that histidine is explicitly discussed as a buffer, with a typical concentration of 10-50 mM (table 2, p288).
Therefore, it would be obvious to add the nicotinamide to the formulation of the competing claims, as that material assists in wound healing. Note that the MPEP states that it is obvious to combine two compositions each of which are taught by the prior art as useful for the same purpose, in order to form a third composition to be used for the same purpose (MPEP 2144.06(I)).
Furthermore, it would be obvious to attempt histidine buffer in the stability studies, as Izutsu explicitly suggests that buffer. As there are only a few pharmacologically acceptable buffers appropriate for any given pH, an artisan in this field would attempt this formulation with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
third rejection
Claims 1, 3, 4, 10, and 12-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 9 of copending Application No. 19/118,346 in view of Esfahani et al (Trauma Mon. (2015) 20(4) e18193).
Competing claim 1 describes a formulation comprising a PEDF derived short peptide, which competing claim 3 limits to a Markush group comprising SEQ ID 3, identical with SEQ ID 3 of the examined claims. Competing claim 9 specifies that the formulation comprise histidine. While the competing claims do not give a concentration, that is not considered a patentable distinction (MPEP 2144.05(II)(A))
The difference between the competing claims and the examined claims is that the competing claims do not describe nicotinamide.
Esfahani et al discuss nicotinamide in the context of wound healing (title). This drug has anti-inflammatory and antioxidant properties, and regulates the effects of immunomodulatory proteins (1st page, 1st column, 1st paragraph). Formulations used a 2% gel (1st pate, 2nd column, 2nd paragraph). Note that this is 164 mM nicotinamide (20g/L/122 g/mole). This formulation remarkably improved the closure rate of wounds, and is suggested as a beneficial agent or adjuvant therapy for wound healing (6th page, 1st column, 1st paragraph). This reference teaches nicotinamide is also useful in would therapy.
Therefore, it would be obvious to add the nicotinamide of Esfahani et al, to improve the ability of the formulation to assist in wound healing. As Esfahani et al show that the material will perform that function, an artisan in this field would attempt this modification with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
fourth rejection
Claims 1, 3, 4, 10, and 12-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 8 of copending Application No. 19/119,097 in view of Esfahani et al (Trauma Mon. (2015) 20(4) e18193) and Izutsu (in Therapeutic Proteins (2005) ISBN 1-58829-390-4).
Competing claim 1 describes a formulation for treating osteoarthritis, while competing claim 4 specifies that the formulation comprise SEQ ID 3, identical with SEQ ID 3 of the examined claims. Competing claim 8 requires one of a Markush group of therapeutics added, including a non steroid anti-inflammatory drug.
The difference between the competing claims and the examined claims is that the competing claims do not describe the formulation used.
Esfahani et al discuss nicotinamide in the context of wound healing (title). This drug has anti-inflammatory and antioxidant properties, and regulates the effects of immunomodulatory proteins (1st page, 1st column, 1st paragraph). Formulations used a 2% gel (1st pate, 2nd column, 2nd paragraph). Note that this is 164 mM nicotinamide (20g/L/122 g/mole). This formulation remarkably improved the closure rate of wounds, and is suggested as a beneficial agent or adjuvant therapy for wound healing (6th page, 1st column, 1st paragraph). This reference teaches nicotinamide is a non-steroid anti-inflammatory drug.
Izutsu describes stabilization of therapeutic proteins (title). The first step is to obtain a stability profile in aqueous solutions of different pH and ionic strength, then identify the excipients that affect protein stability (p289 “preformulation studies”). Then, the potential formulations are stress tested (p289, “formulation design”). Note that histidine is explicitly discussed as a buffer, with a typical concentration of 10-50 mM (table 2, p288).
Therefore, it would be obvious to add the nicotinamide to the formulation of the competing claims as an anti-inflammatory drug. As this is a species that fills a genus of the competing claims, an artisan in this field would attempt this addition with a reasonable expectation of success.
Furthermore, it would be obvious to attempt histidine buffer in the stability studies, as Izutsu explicitly suggests that buffer. As there are only a few pharmacologically acceptable buffers appropriate for any given pH, an artisan in this field would attempt this formulation with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
fifth rejection
Claims 1, 3, 4, 10, and 12-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 13 of copending Application No. 18/273,962 (US 20240408171) in view of Esfahani et al (Trauma Mon. (2015) 20(4) e18193) and the MadSci network message board, question of 15 April, 2022..
Competing claim 1 describes a formulation comprising a PEDF derived short peptide, which competing claim 15 specifies as SEQ ID 3 (identical with SEQ ID 3 of the examined claims). Competing claim 5 specifies a pH of 6.5-7.5.
The difference between the competing claims and the examined claims is that the competing claims do not describe the claimed formulation.
Esfahani et al discuss nicotinamide in the context of wound healing (title). This drug has anti-inflammatory and antioxidant properties, and regulates the effects of immunomodulatory proteins (1st page, 1st column, 1st paragraph). Formulations used a 2% gel (1st pate, 2nd column, 2nd paragraph). Note that this is 164 mM nicotinamide (20g/L/122 g/mole). This formulation remarkably improved the closure rate of wounds, and is suggested as a beneficial agent or adjuvant therapy for wound healing (6th page, 1st column, 1st paragraph). This reference teaches nicotinamide is also useful in would therapy.
The MadSci network answers a question about histidine buffers (title). The pKa of histidine is 6.0; this is the only amino acid that buffers at physiological pH (3d paragraph). Note that this is within the same pH range as discussed by Tsao et al.
Therefore, it would be obvious to add the nicotinamide of Esfahani et al, to improve the ability of the formulation to assist in wound healing. As Esfahani et al show that the material will perform that function, an artisan in this field would attempt this modification with a reasonable expectation of success.
Furthermore, it would be obvious to use the histidine buffer of the MadSci network to buffer the formulations of the competing claims As this buffer buffers in the same range as described as optimum by Tsao et al, an artisan in this field would attempt this modification with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
sixth rejection
Claims 1, 3, 4, 10, and 12-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, and 8 of copending Application No. 18/562,810 (US 20240261379) in view of Esfahani et al (Trauma Mon. (2015) 20(4) e18193).
Competing claim 1 describes a formulation comprising a PEDF derived short peptide, which competing claim 6 limits to a Markush group comprising SEQ ID 3, identical with SEQ ID 3 of the examined claims, and a Markush group of buffers, including histidine. Competing claim 8 specifies that buffer concentration be between 1 and 200 mM, overlapping with the range of the examined claims.
The difference between the competing claims and the examined claims is that the competing claims do not describe nicotinamide.
Esfahani et al discuss nicotinamide in the context of wound healing (title). This drug has anti-inflammatory and antioxidant properties, and regulates the effects of immunomodulatory proteins (1st page, 1st column, 1st paragraph). Formulations used a 2% gel (1st pate, 2nd column, 2nd paragraph). Note that this is 164 mM nicotinamide (20g/L/122 g/mole). This formulation remarkably improved the closure rate of wounds, and is suggested as a beneficial agent or adjuvant therapy for wound healing (6th page, 1st column, 1st paragraph). This reference teaches nicotinamide is also useful in would therapy.
Therefore, it would be obvious to add the nicotinamide of Esfahani et al, to improve the ability of the formulation to assist in wound healing. As Esfahani et al show that the material will perform that function, an artisan in this field would attempt this modification with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached on 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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