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
Applicants elected the formulation of table 22 without traverse in the reply filed on 20 March, 2024.
Claims Status
Claims 1-5, 15, 16, and 25-27 are pending.
Claims 1, 15, 16, and 27 have been amended.
Claims 16, 25 and 26 have been withdrawn due to an election/restriction requirement.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-5, 15, and 27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The rejected claims all use the transition phrase “consists essentially of.” This is interpreted as limiting the scope of the claim to the specified materials and those do not materially affect the basic and novel characteristics of the claimed invention (MPEP 2111.03(III)). However, applicants have not described in their disclosure what the basic and novel characteristics of the claimed invention is. It does not appear to be the pH or osmolarity, note p26, 5th paragraph to p27, 2nd paragraph, which have a different pH and osmolarity. It does not appear to be the excipients, the formulations of p26 and 27 do not list the excipients, and acetate buffer does not buffer at that pH. It is not the polypeptide; there are a number of prior references that describe more or less the same process used to make the protein and the same proteins. Because it is not clear what the transition phrase excludes, the claim is indefinite.
response to applicant’s arguments
Applicants state what they think the claim requires and excludes.
Applicant's arguments filed 13 Feb, 2026 have been fully considered but they are not persuasive.
Applicants have stated what they believe the claim requires and excludes. However, the requirement is that the basic and novel characteristics be clear from the disclosure, not applicant’s later opinion of what that is. While what applicants are arguing is supported by the specification to the point where it can be the basis of a claim amendment, the disclosure does not state that it is what applicants believe to be the basic and novel characteristics of the invention.
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) 1-5, 15, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Lawrence et al (US 20160331815) in view of Zbacnik et al (J. Pharm. Sci. (2017) 106(3) p713-733, cited by applicants), Knauer osmometer sales literature (2014), and Nema (Pfizer presentation, available 2011).
Lawrence et al discuss fibroin derived protein compositions (title). Note that this is a CON of a reference that applicants state show how to make their fibroin compositions (9th page, 3d paragraph). The definition of fibroin derived protein composition is identical with applicants: materials prepared by reacting a silk fibroin protein with heat and pressure with a high concentration of a heavy salt solution (paragraph 40). This causes cleavage at Ser and Cys residues, resulting in the elimination of those amino acids at the site of reaction (Scheme 1, p5). This causes loss of the disulfide bonds holding the fibroin chains together (paragraph 43) (cysteine disulfide bonds between the fibroin heavy and fibroin light protein chains of the fibroin derived protein are reduced or eliminated). This loss of serine and cysteine residues causes a corresponding increase in the amount of Gly and Ala residues; the composition differs by at least 4% with respect to Ser, Gly, and Ala residues (paragraph 57), other embodiments vary by at least 6% (paragraph 58) (wherein the primary amino acid sequences of the fibroin derived protein composition differ from native fibroin by at least 4% with respect to the absolute values of the combined differences in amino acid content of serine, glycine, and alanine). Serine content can be reduced by greater than 25%, or greater than 45%, compared to the native protein (paragraph 63)(the protein composition has a serine content that is reduced by greater than 25% compared to native fibroin). The proteins contain less than 8% serine amino acid residues (paragraph 68) (wherein the serine content is at least about 5%). Average molecular weight can be below 96 kDa (paragraph 10), overlapping with that claimed by applicants, or between about 25 kDa and 100 kDa (paragraph 57), a range adjacent to that claimed by applicants (the average molecular weight of the fibroin derived protein composition is between 15 kDa and 22 kDa). The glycine content can be over 46% or 48% (paragraph 69), while the alanine content can be above 30% (paragraph 70). The formulations can contain a buffering agent, a demulcent agent, and a stabilizing agent (paragraph 100), with polysorbate 80 explicitly described as a demulcent agent that can be used in the invention (paragraph 100), and magnesium chloride listed as a buffering agent (paragraph 101). Among the uses for this material is treatment of dry eye syndrome, at concentrations between 0.5 to 2% by weight (paragraph 99). An example mentions various materials sealed in glass beakers (paragraph 119).
The difference between this reference and the examined claims is that this reference does not disclose acetate buffer, the pH, or dextrose in the formulation.
Zbacnik et al discuss buffers in protein formulations (title). In addition to pH stabilization, buffers can stabilize proteins by a number of other mechanisms (abstract), although often the other mechanism is not known (p715, 2nd column, 3d paragraph). This behavior works in conjunction with other excipients (p715, 1st column, 2nd and 3d paragraphs). PH affects protein stability more than any other factor (p715, 1st column, 4th paragraph); presumably, optimizing the pH for stability will be first, then selecting the buffer that is appropriate for that pH that also stabilizes the protein. Among the common buffers used for this purpose is acetate (table 1, p1=714, 1st column, top of page, and table 3, p716, 1st column, top of page). There is a long discussion of examples of how different buffers stabilize different proteins (p717, 1st column, 2nd paragraph, continues to p720, 1st column, 3d paragraph). One must assess protein stability in the presence of different buffers at a constant pH and, if possible, ionic strength to find preferential ones (p726, 2nd column, 2nd paragraph).
Knauer discuss dry eye syndrome, the same issue discussed by Lawrence et al, and discuss measuring the osmolarity of eye drops used to treat the disorder. Hypotonic and hypertonic solutions can cause eye pain, with tonicity tolerance being between 0.7 to 1.4% NaCl solution (119-240 mOsm/Kg) (1st page, 5th paragraph). Hypertonic solutions are more tolerable, because they are diluted by tear fluid (2nd page, 1st paragraph). This reference discusses tonicity in the context of eye drops, and places limitations on this parameter.
Nema discusses formulation of protein drugs (title). A small number of tonicity modifiers are mentioned, including dextrose (5th page). This reference discusses applicant’s elected tonicity modifier.
Therefore, it would be obvious to optimize the pH and buffer for the formulations of Lawrence et al, to optimize the stability of the polypeptide formulations. As this is merely following the directions of Zbacnik et al, which is generic as to the polypeptide, an artisan in this field would attempt this optimization with a reasonable expectation of success.
Furthermore, once the pH is optimized, it would be obvious to try the buffers appropriate for the optimum pH to find the buffer that yields the highest stability, as discussed by Zbacnik et al. As the different buffers are likely to have different effects on stability, an artisan in this field would attempt this process with a reasonable expectation of success.
Finally, it would be obvious to use the tonicity modifier of Nema et al, as a combination of known elements (tonicity modifiers) yielding expected results (tonicity appropriate for the application). As the Knauer sales literature give the parameters for tonicity that are appropriate, an artisan in this field would attempt this modification with a reasonable expectation of success.
Lawrence et al teaches the same polypeptide as the examined claims, and suggests formulations with magnesium chloride and polysorbate 80 at polypeptide concentrations that overlap with those of the examined claims. The molecular weight range of the polypeptides of Lawrence et al is either overlapping or adjacent to the molecular weight range claimed by applicants; either of which renders the limitation obvious (MPEP 2144.05(I)). Zbacnik et al render obvious finding the optimum pH. Knauer discusses the optimum osmolarity for the application of Lawrence et al, and Nema renders obvious adding dextrose. The MPEP states that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or working ranges by routine experimentation" In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) (MPEP2144.05.II). Note that many of these modifications are based on increasing stability; this means an improved stability would be expected. Zbacnik et al discuss acetate buffer. Thus, the combination of references renders obvious claims 1-5 and 27.
Lawrence et al discuss borosilicate glass storage containers, rendering obvious claim 15.
response to applicant’s arguments
Applicants argue that the amount of polysorbate 80 used is exceptionally small for the stability achieved.
Applicant's arguments filed 13 Feb, 2026 have been fully considered but they are not persuasive.
Applicants have presented no evidence that the amount of polysorbate is exceptionally low. Note that Andya et al (US 20060088523, cited by applicants) discusses using 0.001% to about 1%, preferably 0.01% to 0.1% -- greatly overlapping with the range claimed by applicants.
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 1-5, 15, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 6, and 8 of U. S. Patent No. 12,350,321 in view of Zbacnik et al (J. Pharm. Sci. (2017) 106(3) p713-733, cited by applicants), Knauer osmometer sales literature (2014), and Ostrow et al (US 20190091213).
Competing claim 1 describes a fibroin derived protein by product by process limitations, that meet the definition of fibroin derived protein in the examined application. It also specifies that cysteine disulfide bonds are reduced or eliminated, and has an average molecular weight of less than 100 kDa (overlapping with the instant claims), and that it comprises between 4.5 and 7.5% serine, while claim 5 specifies the sequence differs by at least 8% with respect to the amount of serine, glycine, and alanine. Competing claim 6 specifies at least 46.5% glycine residues, while competing claim 8 specifies at least 30% alanine residues. This material appears to be a genus that includes the material used in the examined claims.
The difference between the competing claims and the examined claims is that the competing claims do not discuss a formulation.
Knauer discuss dry eye syndrome, and discuss measuring the osmolarity of eye drops used to treat the disorder. Hypotonic and hypertonic solutions can cause eye pain (1st page, 5th paragraph). Hypertonic solutions are more tolerable, because they are diluted by tear fluid (2nd page, 1st paragraph). This reference discusses tonicity in the context of eye drops, and places limitations on this parameter.
Ostrow et al discuss ophthalmic compositions (title). Among the tonicity adjustments described are magnesium chloride and dextrose (paragraph 21). In addition, polysorbate 80 is listed as a stabilizer to inhibit degradation of the ophthalmic agent (paragraph 170)
Therefore, it would be obvious to optimize the pH and buffer for the formulations of Lawrence et al, to optimize the stability of the polypeptide formulations. As this is merely following the directions of Zbacnik et al, which is generic as to the polypeptide, an artisan in this field would attempt this optimization with a reasonable expectation of success.
Furthermore, once the pH is optimized, it would be obvious to try the buffers appropriate for the optimum pH to find the buffer that yields the highest stability, as discussed by Zbacnik et al. As the different buffers are likely to have different effects on stability, an artisan in this field would attempt this process with a reasonable expectation of success.
In addition, it would be obvious to use the tonicity modifiers of Ostrow et al, to adjust the tonicity of the formulation to a safe level. As the Knauer sales literature give the parameters for tonicity that are appropriate, an artisan in this field would attempt this modification with a reasonable expectation of success.
Finally, it would be obvious to add polysorbate 80 to the formulation, to stabilize the material, as mentioned by Ostrow et al. As this excipient is commonly used for this purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants argue that the cited prior art does not discuss extended shelf life and improved solubility, and that the amount of polysorbate 80 used is very low.
Applicant's arguments filed 13 Feb, 2026 have been fully considered but they are not persuasive.
Applicants argue that the cited prior art does not discuss improved stability. This is incorrect; Zbacnik et al discuss optimizing this parameter.
Applicants argue that the amount of polysorbate 80 is low. Applicants have not demonstrated that a person of skill in the art would consider the amount of polysorbate 80 to be small.
second rejection
Claims 1-5, 15, and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-7, and 10 of copending Application No. 17/666,268 (US 20220332773) in view of Zbacnik et al (J. Pharm. Sci. (2017) 106(3) p713-733, cited by applicants), Knauer osmometer sales literature (2014), and Ostrow et al (US 20190091213).
Competing claim 1 describes a fibroin derived protein, and specifies that cysteine disulfide bonds are reduced or eliminated, and has an average molecular between 60 kDa and 10 kDa (overlapping with the instant claims). Competing claim 5 requires that the material have less than 8% serine residues, claim 10 specifies at least 46.5% glycine residues, and competing claim 7 specifies at least 30% alanine residues. This material appears to be a genus that includes the material used in the examined claims. Competing claim 10 requires that the material be an ophthalmic formulation comprising this material and water, with optionally one or more of a buffer, salt, stabilizer, preservative, and lubricant.
The difference between the competing claims and the examined claims is that the competing claims do not discuss a the buffer, surfactant, or tonicity modifiers of the examined claims.
Knauer discuss dry eye syndrome, and discuss measuring the osmolarity of eye drops used to treat the disorder. Hypotonic and hypertonic solutions can cause eye pain (1st page, 5th paragraph). Hypertonic solutions are more tolerable, because they are diluted by tear fluid (2nd page, 1st paragraph). This reference discusses tonicity in the context of eye drops, and places limitations on this parameter.
Ostrow et al discuss ophthalmic compositions (title). Among the tonicity adjustments described are magnesium chloride and dextrose (paragraph 21). In addition, polysorbate 80 is listed as a stabilizer to inhibit degradation of the ophthalmic agent (paragraph 170)
Therefore, it would be obvious to optimize the pH and buffer for the formulations of Lawrence et al, to optimize the stability of the polypeptide formulations. As this is merely following the directions of Zbacnik et al, which is generic as to the polypeptide, an artisan in this field would attempt this optimization with a reasonable expectation of success.
Furthermore, once the pH is optimized, it would be obvious to try the buffers appropriate for the optimum pH to find the buffer that yields the highest stability, as discussed by Zbacnik et al. As the different buffers are likely to have different effects on stability, an artisan in this field would attempt this process with a reasonable expectation of success.
In addition, it would be obvious to use the tonicity modifiers of Ostrow et al, to adjust the tonicity of the formulation to a safe level. As the Knauer sales literature give the parameters for tonicity that are appropriate, an artisan in this field would attempt this modification with a reasonable expectation of success.
Finally, it would be obvious to add polysorbate 80 to the formulation, to stabilize the material, as mentioned by Ostrow et al. As this excipient is commonly used for this purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
response to applicant’s arguments
Applicants have repeated the arguments presented for the first double patenting rejection, which were answered there.
third rejection
Claims 1-5, 15, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of US Patent No. 10,953,132 in view of Zbacnik et al (J. Pharm. Sci. (2017) 106(3) p713-733, cited by applicants), Knauer osmometer sales literature (2014), and Ostrow et al (US 20190091213).
Competing claim 1 describes a method of treating an ocular wound, using a fibroin derived protein, with limitations of MW, serine content, and amino acid content very similar to that of the instant claims. Competing claim 2 requires that the cysteine disulfide bonds be reduced or eliminated. This appears to be the same material or a genus that includes the same material of the examined claims.
The difference between the competing claims and the examined claims is that the competing claims do not discuss the formulation.
Knauer discuss dry eye syndrome, and discuss measuring the osmolarity of eye drops used to treat the disorder. Hypotonic and hypertonic solutions can cause eye pain (1st page, 5th paragraph). Hypertonic solutions are more tolerable, because they are diluted by tear fluid (2nd page, 1st paragraph). This reference discusses tonicity in the context of eye drops, and places limitations on this parameter.
Ostrow et al discuss ophthalmic compositions (title). Among the tonicity adjustments described are magnesium chloride and dextrose (paragraph 21). In addition, polysorbate 80 is listed as a stabilizer to inhibit degradation of the ophthalmic agent (paragraph 170)
Therefore, it would be obvious to optimize the pH and buffer for the formulations of Lawrence et al, to optimize the stability of the polypeptide formulations. As this is merely following the directions of Zbacnik et al, which is generic as to the polypeptide, an artisan in this field would attempt this optimization with a reasonable expectation of success.
Furthermore, once the pH is optimized, it would be obvious to try the buffers appropriate for the optimum pH to find the buffer that yields the highest stability, as discussed by Zbacnik et al. As the different buffers are likely to have different effects on stability, an artisan in this field would attempt this process with a reasonable expectation of success.
In addition, it would be obvious to use the tonicity modifiers of Ostrow et al, to adjust the tonicity of the formulation to a safe level. As the Knauer sales literature give the parameters for tonicity that are appropriate, an artisan in this field would attempt this modification with a reasonable expectation of success.
Finally, it would be obvious to add polysorbate 80 to the formulation, to stabilize the material, as mentioned by Ostrow et al. As this excipient is commonly used for this purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants have repeated the arguments presented for the first double patenting rejection, which were answered there.
fourth rejection
Claims 1-5, 15, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, and 9 of US Patent No. 11,242,367 in view of Zbacnik et al (J. Pharm. Sci. (2017) 106(3) p713-733, cited by applicants), Knauer osmometer sales literature (2014), and Ostrow et al (US 20190091213).
Competing claim 1 describes a fibroin derived protein composition, and specifies that cysteine disulfide bonds are reduced or eliminated, and has an average molecular between 40 kDa and 10 kDa (almost identical with the instant claims), and requires that the serine content is at least about 5%. Competing claim requires that the material have less than 8% serine residues, claim 4 specifies at least 46.5% glycine residues, and competing claim 5 specifies at least 30% alanine residues. This material appears to be the same material used in the examined claims. Competing claim 9 requires that the material be an ophthalmic formulation comprising this material and water, with optionally one or more of a buffer, salt, stabilizer, preservative, and lubricant.
The difference between the competing claims and the examined claims is that the competing claims do not discuss a buffer, surfactant, or tonicity modifiers of the examined claims.
Knauer discuss dry eye syndrome, and discuss measuring the osmolarity of eye drops used to treat the disorder. Hypotonic and hypertonic solutions can cause eye pain (1st page, 5th paragraph). Hypertonic solutions are more tolerable, because they are diluted by tear fluid (2nd page, 1st paragraph). This reference discusses tonicity in the context of eye drops, and places limitations on this parameter.
Ostrow et al discuss ophthalmic compositions (title). Among the tonicity adjustments described are magnesium chloride and dextrose (paragraph 21). In addition, polysorbate 80 is listed as a stabilizer to inhibit degradation of the ophthalmic agent (paragraph 170)
Therefore, it would be obvious to optimize the pH and buffer for the formulations of Lawrence et al, to optimize the stability of the polypeptide formulations. As this is merely following the directions of Zbacnik et al, which is generic as to the polypeptide, an artisan in this field would attempt this optimization with a reasonable expectation of success.
Furthermore, once the pH is optimized, it would be obvious to try the buffers appropriate for the optimum pH to find the buffer that yields the highest stability, as discussed by Zbacnik et al. As the different buffers are likely to have different effects on stability, an artisan in this field would attempt this process with a reasonable expectation of success.
In addition, it would be obvious to use the tonicity modifiers of Ostrow et al, to adjust the tonicity of the formulation to a safe level. As the Knauer sales literature give the parameters for tonicity that are appropriate, an artisan in this field would attempt this modification with a reasonable expectation of success.
Finally, it would be obvious to add polysorbate 80 to the formulation, to stabilize the material, as mentioned by Ostrow et al. As this excipient is commonly used for this purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants have repeated the arguments presented for the first double patenting rejection, which were answered there.
fifth rejection
Claims 1-5, 15, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14 and 16 of US Patent No. 11,045,524 in view of Zbacnik et al (J. Pharm. Sci. (2017) 106(3) p713-733, cited by applicants), Knauer osmometer sales literature (2014), and Ostrow et al (US 20190091213).
Competing claim 14 describes an ophthalmic formulation fibroin derived protein that appears to be a genus that includes the material used in the examined claims. Competing claim 16 requires that the formulation comprise one or more of a buffering agent, a stabilizing agent, and a demulcent.
The difference between the competing claims and the examined claims is that the competing claims do not discuss the buffer, surfactant, or tonicity modifiers of the examined claims.
Knauer discuss dry eye syndrome, and discuss measuring the osmolarity of eye drops used to treat the disorder. Hypotonic and hypertonic solutions can cause eye pain (1st page, 5th paragraph). Hypertonic solutions are more tolerable, because they are diluted by tear fluid (2nd page, 1st paragraph). This reference discusses tonicity in the context of eye drops, and places limitations on this parameter.
Ostrow et al discuss ophthalmic compositions (title). Among the tonicity adjustments described are magnesium chloride and dextrose (paragraph 21). In addition, polysorbate 80 is listed as a stabilizer to inhibit degradation of the ophthalmic agent (paragraph 170)
Therefore, it would be obvious to optimize the pH and buffer for the formulations of Lawrence et al, to optimize the stability of the polypeptide formulations. As this is merely following the directions of Zbacnik et al, which is generic as to the polypeptide, an artisan in this field would attempt this optimization with a reasonable expectation of success.
Furthermore, once the pH is optimized, it would be obvious to try the buffers appropriate for the optimum pH to find the buffer that yields the highest stability, as discussed by Zbacnik et al. As the different buffers are likely to have different effects on stability, an artisan in this field would attempt this process with a reasonable expectation of success.
In addition, it would be obvious to use the tonicity modifiers of Ostrow et al, to adjust the tonicity of the formulation to a safe level. As the Knauer sales literature give the parameters for tonicity that are appropriate, an artisan in this field would attempt this modification with a reasonable expectation of success.
Finally, it would be obvious to add polysorbate 80 to the formulation, to stabilize the material, as mentioned by Ostrow et al. As this excipient is commonly used for this purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants have repeated the arguments presented for the first double patenting rejection, which were answered there.
sixth rejection
Claims 1-5, 15, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of US Patent No. 11,890,328 in view of Zbacnik et al (J. Pharm. Sci. (2017) 106(3) p713-733, cited by applicants), Knauer osmometer sales literature (2014), and Ostrow et al (US 20190091213).
Competing claim 1 describes an ophthalmic formulation fibroin derived protein that appears to be a genus that includes the material used in the examined claims. Competing claim 16 requires that the formulation comprise one or more of a buffering agent, a stabilizing agent, and a demulcent.
The difference between the competing claims and the examined claims is that the competing claims do not discuss the buffer, surfactant, or tonicity modifiers of the examined claims.
Knauer discuss dry eye syndrome, and discuss measuring the osmolarity of eye drops used to treat the disorder. Hypotonic and hypertonic solutions can cause eye pain (1st page, 5th paragraph). Hypertonic solutions are more tolerable, because they are diluted by tear fluid (2nd page, 1st paragraph). This reference discusses tonicity in the context of eye drops, and places limitations on this parameter.
Ostrow et al discuss ophthalmic compositions (title). Among the tonicity adjustments described are magnesium chloride and dextrose (paragraph 21). In addition, polysorbate 80 is listed as a stabilizer to inhibit degradation of the ophthalmic agent (paragraph 170)
Therefore, it would be obvious to optimize the pH and buffer for the formulations of Lawrence et al, to optimize the stability of the polypeptide formulations. As this is merely following the directions of Zbacnik et al, which is generic as to the polypeptide, an artisan in this field would attempt this optimization with a reasonable expectation of success.
Furthermore, once the pH is optimized, it would be obvious to try the buffers appropriate for the optimum pH to find the buffer that yields the highest stability, as discussed by Zbacnik et al. As the different buffers are likely to have different effects on stability, an artisan in this field would attempt this process with a reasonable expectation of success.
In addition, it would be obvious to use the tonicity modifiers of Ostrow et al, to adjust the tonicity of the formulation to a safe level. As the Knauer sales literature give the parameters for tonicity that are appropriate, an artisan in this field would attempt this modification with a reasonable expectation of success.
Finally, it would be obvious to add polysorbate 80 to the formulation, to stabilize the material, as mentioned by Ostrow et al. As this excipient is commonly used for this purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants have repeated the arguments presented for the first double patenting rejection, which were answered there.
seventh rejection
Claims 1-5, 15, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6-11 of US Patent No. 9,394,355 in view of Zbacnik et al (J. Pharm. Sci. (2017) 106(3) p713-733, cited by applicants), Knauer osmometer sales literature (2014), and Ostrow et al (US 20190091213).
Competing claim 1 describes an ophthalmic formulation fibroin derived protein with product by process limitations and a MW range that overlaps with that of the material used in the examined claims. Competing claims 6-11 provide more details with respect to amino acid composition, all of which is consistent with the material of the examined claims.
The difference between the competing claims and the examined claims is that the competing claims do not discuss the buffer, surfactant, or tonicity modifiers of the examined claims.
Knauer discuss dry eye syndrome, and discuss measuring the osmolarity of eye drops used to treat the disorder. Hypotonic and hypertonic solutions can cause eye pain (1st page, 5th paragraph). Hypertonic solutions are more tolerable, because they are diluted by tear fluid (2nd page, 1st paragraph). This reference discusses tonicity in the context of eye drops, and places limitations on this parameter.
Ostrow et al discuss ophthalmic compositions (title). Among the tonicity adjustments described are magnesium chloride and dextrose (paragraph 21). In addition, polysorbate 80 is listed as a stabilizer to inhibit degradation of the ophthalmic agent (paragraph 170)
Therefore, it would be obvious to optimize the pH and buffer for the formulations of Lawrence et al, to optimize the stability of the polypeptide formulations. As this is merely following the directions of Zbacnik et al, which is generic as to the polypeptide, an artisan in this field would attempt this optimization with a reasonable expectation of success.
Furthermore, once the pH is optimized, it would be obvious to try the buffers appropriate for the optimum pH to find the buffer that yields the highest stability, as discussed by Zbacnik et al. As the different buffers are likely to have different effects on stability, an artisan in this field would attempt this process with a reasonable expectation of success.
In addition, it would be obvious to use the tonicity modifiers of Ostrow et al, to adjust the tonicity of the formulation to a safe level. As the Knauer sales literature give the parameters for tonicity that are appropriate, an artisan in this field would attempt this modification with a reasonable expectation of success.
Finally, it would be obvious to add polysorbate 80 to the formulation, to stabilize the material, as mentioned by Ostrow et al. As this excipient is commonly used for this purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants have repeated the arguments presented for the first double patenting rejection, which were answered there.
eighth rejection
Claims 1-5, 15, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of US Patent No. 9,907,836 in view of Zbacnik et al (J. Pharm. Sci. (2017) 106(3) p713-733, cited by applicants), Knauer osmometer sales literature (2014), and Ostrow et al (US 20190091213).
Competing claim 1 describes an ophthalmic formulation fibroin derived protein that appears to be a genus that includes the material used in the examined claims. Competing claim 3 requires that the formulation comprise one or more of a buffering agent, a stabilizing agent, and a demulcent.
The difference between the competing claims and the examined claims is that the competing claims do not discuss the buffer, surfactant, or tonicity modifiers of the examined claims.
Knauer discuss dry eye syndrome, and discuss measuring the osmolarity of eye drops used to treat the disorder. Hypotonic and hypertonic solutions can cause eye pain (1st page, 5th paragraph). Hypertonic solutions are more tolerable, because they are diluted by tear fluid (2nd page, 1st paragraph). This reference discusses tonicity in the context of eye drops, and places limitations on this parameter.
Ostrow et al discuss ophthalmic compositions (title). Among the tonicity adjustments described are magnesium chloride and dextrose (paragraph 21). In addition, polysorbate 80 is listed as a stabilizer to inhibit degradation of the ophthalmic agent (paragraph 170)
Therefore, it would be obvious to optimize the pH and buffer for the formulations of Lawrence et al, to optimize the stability of the polypeptide formulations. As this is merely following the directions of Zbacnik et al, which is generic as to the polypeptide, an artisan in this field would attempt this optimization with a reasonable expectation of success.
Furthermore, once the pH is optimized, it would be obvious to try the buffers appropriate for the optimum pH to find the buffer that yields the highest stability, as discussed by Zbacnik et al. As the different buffers are likely to have different effects on stability, an artisan in this field would attempt this process with a reasonable expectation of success.
In addition, it would be obvious to use the tonicity modifiers of Ostrow et al, to adjust the tonicity of the formulation to a safe level. As the Knauer sales literature give the parameters for tonicity that are appropriate, an artisan in this field would attempt this modification with a reasonable expectation of success.
Finally, it would be obvious to add polysorbate 80 to the formulation, to stabilize the material, as mentioned by Ostrow et al. As this excipient is commonly used for this purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants have repeated the arguments presented for the first double patenting rejection, which were answered there.
ninth rejection
Claims 1-5, 15, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-10 of US Patent No. 10,471,128 in view of Zbacnik et al (J. Pharm. Sci. (2017) 106(3) p713-733, cited by applicants), Knauer osmometer sales literature (2014), and Ostrow et al (US 20190091213).
Competing claim 1 describes a fibroin derived protein composition that appears similar to that of the examined claims. Competing claims 5-10 specify amino acid compositions that are also similar to that of the examined claims. This appears to be a genus that includes the material used in the examined claims.
The difference between the competing claims and the examined claims is that the competing claims do not discuss the buffer, surfactant, or tonicity modifiers of the examined claims.
Knauer discuss dry eye syndrome, and discuss measuring the osmolarity of eye drops used to treat the disorder. Hypotonic and hypertonic solutions can cause eye pain (1st page, 5th paragraph). Hypertonic solutions are more tolerable, because they are diluted by tear fluid (2nd page, 1st paragraph). This reference discusses tonicity in the context of eye drops, and places limitations on this parameter.
Ostrow et al discuss ophthalmic compositions (title). Among the tonicity adjustments described are magnesium chloride and dextrose (paragraph 21). In addition, polysorbate 80 is listed as a stabilizer to inhibit degradation of the ophthalmic agent (paragraph 170)
Therefore, it would be obvious to optimize the pH and buffer for the formulations of Lawrence et al, to optimize the stability of the polypeptide formulations. As this is merely following the directions of Zbacnik et al, which is generic as to the polypeptide, an artisan in this field would attempt this optimization with a reasonable expectation of success.
Furthermore, once the pH is optimized, it would be obvious to try the buffers appropriate for the optimum pH to find the buffer that yields the highest stability, as discussed by Zbacnik et al. As the different buffers are likely to have different effects on stability, an artisan in this field would attempt this process with a reasonable expectation of success.
In addition, it would be obvious to use the tonicity modifiers of Ostrow et al, to adjust the tonicity of the formulation to a safe level. As the Knauer sales literature give the parameters for tonicity that are appropriate, an artisan in this field would attempt this modification with a reasonable expectation of success.
Finally, it would be obvious to add polysorbate 80 to the formulation, to stabilize the material, as mentioned by Ostrow et al. As this excipient is commonly used for this purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
response to applicant’s arguments
Applicants have repeated the arguments presented for the first double patenting rejection, which were answered there.
New Rejections
Double Patenting
The legal basis for double patenting rejections was given above, and will not be repeated here.
Claims 1-5, 15, and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 6, and 8 of US Application No. 19/259,889 in view of Zbacnik et al (J. Pharm. Sci. (2017) 106(3) p713-733, cited by applicants), Knauer osmometer sales literature (2014), and Ostrow et al (US 20190091213). While this is a new rejection, it is based on an application filed by applicants. As applicants are reasonably expected to know what they have submitted, this will not negate the finality of this office action.
Competing claim 1 describes a fibroin derived protein composition, while competing claims 2, 5, 6, and 8 give additional information regarding amino acid compositions that are similar to the examined protein. This appears to be the same material used in the examined claims.
The difference between the competing claims and the examined claims is that the competing claims do not discuss the buffer, surfactant, or tonicity modifiers of the examined claims.
Knauer discuss dry eye syndrome, and discuss measuring the osmolarity of eye drops used to treat the disorder. Hypotonic and hypertonic solutions can cause eye pain (1st page, 5th paragraph). Hypertonic solutions are more tolerable, because they are diluted by tear fluid (2nd page, 1st paragraph). This reference discusses tonicity in the context of eye drops, and places limitations on this parameter.
Ostrow et al discuss ophthalmic compositions (title). Among the tonicity adjustments described are magnesium chloride and dextrose (paragraph 21). In addition, polysorbate 80 is listed as a stabilizer to inhibit degradation of the ophthalmic agent (paragraph 170)
Therefore, it would be obvious to optimize the pH and buffer for the formulations of Lawrence et al, to optimize the stability of the polypeptide formulations. As this is merely following the directions of Zbacnik et al, which is generic as to the polypeptide, an artisan in this field would attempt this optimization with a reasonable expectation of success.
Furthermore, once the pH is optimized, it would be obvious to try the buffers appropriate for the optimum pH to find the buffer that yields the highest stability, as discussed by Zbacnik et al. As the different buffers are likely to have different effects on stability, an artisan in this field would attempt this process with a reasonable expectation of success.
In addition, it would be obvious to use the tonicity modifiers of Ostrow et al, to adjust the tonicity of the formulation to a safe level. As the Knauer sales literature give the parameters for tonicity that are appropriate, an artisan in this field would attempt this modification with a reasonable expectation of success.
Finally, it would be obvious to add polysorbate 80 to the formulation, to stabilize the material, as mentioned by Ostrow et al. As this excipient is commonly used for this purpose, an artisan in this field would attempt this modification with a reasonable expectation of success.
Conclusion
THIS ACTION IS MADE FINAL. 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 FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658