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 .
Election/Restriction/Status of Claims
Applicant’s election of Group III (claims 28-41) in the reply filed on 08/11/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Furthermore, Applicants amendments to the claims are acknowledged. Claims 1-27 and 42-69 are withdrawn. Claims 28-41 are pending and examined on the merits herein.
Priority
The instant application filed 03/16/2023, claims priority to Provisional Application No. 63/321,287, filed 03/18/2022.
Information Disclosure Statement
No Information Disclosure Statement (IDS) has been submitted at the time of the instant office action.
Claim Objections
Claims 28-41 are objected to because of the following informality: The claims recite an RKI without specifying what the abbreviation stands for. Examiner has interpreted an RKI as a Rho Kinase Inhibitor in line with the instant specification. Please define the abbreviation in the claims as well. Appropriate correction is required.
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 28-41 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 claims recite various concentrations in terms of percent, however, the claims do not specify the basis for these percents nor the percent unit. For example, do the percentages refer to a weight by weight percentage or a weight by volume percentage? Are the percentages based on the total weight of the composition or on the weight of a different component? As such, the claims are indefinite.
The term “normal state” in claim 35 is a relative term which renders the claim indefinite. The term “normal” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The rehabilitation of stressed or damaged ocular tissue to a normal state is relative to what is normal for a given individual. Does normal refer to the state of the tissue prior to being stressed or damaged or does normal refer to a state that would allow one to perform basic functions? Furthermore, claim 35 recites “fully or partially rehabilitating” the tissue to a normal state. The terms “fully” and “partially” cannot be determined without understanding what the “normal state” is. For the sake of compact prosecution a “normal state” will be interpreted as the original state of the tissue, prior to becoming stressed or damaged.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
1. Claims 28-41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of healing or rehabilitating the cornea, specifically methods of reducing corneal edema and improving visual acuity in FCD patients and methods of conditioning a donor cornea prior to transplantation, does not reasonably provide enablement for healing all types of ocular tissue after any trauma nor fully rehabilitating all types of damaged ocular tissues to its original state. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. §112, first paragraph, have been described In re Wands, 8 USPQ2d 1400(1988). They are:
1. The breadth of the claims;
2. The nature of the invention;
3. The state of the prior art;
4. The predictability or lack thereof in the art
5. The level of skill in the art;
6. The amount of direction or guidance present;
7. The presence or absence of working examples;
8. The quantity of experimentation needed.
The breadth of the claims
The breadth of the claims seems to encompass methods of promoting healing of all ocular tissues in a mammal after all types of trauma and fully or partially rehabilitating stressed or damaged ocular tissue to a normal state. The specification does not describe methods of promoting healing of any tissue other than the cornea nor does the specification describe methods of promoting healing after all types of trauma. Lastly, the specification does not describe methods of fully rehabilitating all types of damaged ocular tissue to its original state.
The nature of the invention
The nature of the invention as recited in the instant claims is a method of promoting healing of ocular tissue of a mammal after trauma and a method of fully or partially rehabilitating stressed or damaged ocular tissue to a normal state by administering to the ocular tissue a composition comprising an RKI and other excipients.
The state of the prior art/ The predictability or lack thereof in the art
Ocular tissue can be characterized into several categories starting with the differentiation between external and internal structures. External structures include the conjunctiva and eyelids while the internal structures can be broken into layers. The outermost layer (i.e., surface) of the eye includes the sclera and the cornea, with the middle layer comprising features such as the Iris. The innermost layer comprises the lens, vitreous, and retina (Pradeep et al., PTO-892). Given the structure of an eye, different administration methods and treatments would be necessary to access different types of ocular tissue. For example, a topically applied eye drop would not be capable of treating conditions in the middle or innermost layer of the eye.
Regarding the use of Rho Kinase Inhibitors, RKIs are known therapeutic agents in ophthalmology. Research has found strong evidence demonstrating that inhibition of Rho kinase significantly decreases IOP (intraocular pressure) for treating glaucoma, increases healing of the corneal endothelium, and decreases progression of diabetic retinopathy. Regarding the healing of corneal endothelium, sloughing off and apoptosis of corneal endothelial cells in Fuchs’ endothelial corneal dystrophy is one of the major causes of corneal transplantation, with other causes being ocular surgery, inflammation, and trauma. Acute corneal trauma, which occurs during cataract surgeries, can also lead to corneal degeneration. RKIs can be used to increase the proliferation rates of corneal endothelial cells in order to allow for greater density in this layer. This allows for increased healing and migration of corneal endothelial cells to cover the afflicted area. There have been two proposed methods of delivery of RKIs to heal the corneal endothelium, including topical eye drops and an anterior chamber injection with cultured endothelial cells. Diabetic retinopathy on the other hand refers generally to disorders of the retina caused by diabetes while macular edema is a progressed retinopathy. It has been shown that treatment with RKI intravitreal injections would decrease the effects of diabetic retinopathy and macular edema thereby slowing progression. However, additional clinical trials investigating the reviewed treatment options of Rho kinase inhibitors are necessary to further validate previous findings on the topic (Moshirfar et al., PTO-892).
As such, the promotion of healing and rehabilitation of ocular tissue has only been accomplished in the cornea with RKI treatments delivered via topical eye drops or an anterior chamber injection. Damage to the corneal endothelium occurs from ocular surgery, inflammation, and trauma. Retroactive healing/rehabilitation of ocular tissue has yet to be accomplished in tissue other than the cornea. Furthermore, no studies have been done that explicitly recite the full rehabilitation of stressed or damaged ocular tissue, rather these studies have shown improvement, slowed progression, and decreased adverse effects. Therefore, the state of the art for promoting healing or rehabilitating damaged ocular tissue is very unpredictable and dependent on the condition being treated, the targeted tissue, and the desired outcomes. Although there are promising results for healing and rehabilitating ocular tissue with RKIs, more research is necessary to validate these findings.
The level of one of ordinary skill
The level of skill would be high in order to carry out the method of administering an ophthalmic composition to promote healing and rehabilitating damaged ocular tissue.
The amount of direction or guidance present/ The presence or absence of working examples
The only guidance presented in the instant specification is methods of treating the cornea, specifically methods of treating corneal edema [010] and methods of conditioning a donor cornea prior to transplantation [011]. Use of disclosed compositions can comprise administration via methods known in the art such as topical administration [062], however, there is no guidance for injecting the composition into the eye to reach internal tissue. The compositions are cited as useful for protecting the ocular surface (e.g. cornea and conjunctiva), corneal epithelial cells, corneal endothelial cells, and/or other ocular tissue during surgery or other events causing injury to the eye [064] as well as in methods of treating a wound or promoting healing after such event [067]. There is no specific evidence as to what extent of trauma is treatable with the instant method. Working examples include example 2 of the instant specification which discloses soaking a donor cornea in the composition of the invention for 12-24 hours prior to transplantation. This “pre-loads” the tissue with an RKI to accelerate healing post-transplant and increase endothelia cell count (p. 23). There is no data or evidence to suggest that this method accelerates healing or increases cell count, which would be required in order to demonstrate a method for healing and rehabilitating ocular tissue as instantly claimed. Furthermore Example 2 only relates to the cornea, rather than all types of ocular tissue as instantly claimed. Examples 3-5 of the instant specification disclose applying eyedrops to the cornea before or after applying contact lens to the eyes (p. 23). Once again there is no data or evidence to suggest “healing” or “rehabilitation” other than the positive recitation of the composition being “used for rehabilitating the ocular surface” or “enhancing contact lens comfort”. Similarly, the composition is only applied to the ocular surface, rather than all types of ocular tissue as instantly claimed. Example 6 discloses a randomized, open-label, parallel-group study of two dosing regimens of Netarsudil (i.e., RKI eye drops) in patients with Fuchs Corneal Dystrophy (FCD). The purpose of study was to reduce corneal edema and improve visual acuity in patients with FCD. Results of the study are illustrated by FIG. 1, which shows Netarsudil to significantly reduce, and resolve, corneal edema and improve vision in patients with FCD as well as improve corneal thickness (p. 24-25). In order to claim the full scope of healing or rehabilitating all ocular tissue, which has been damaged in any way, working examples of such situations would be required (i.e., treating retinopathy or rehabilitating an eye which has been punctured to its “normal state”). As such, the instant specification only provides clear guidance and examples for methods of treating the cornea, specifically methods of reducing corneal edema and improving visual acuity in FCD patients and methods of conditioning a donor cornea prior to transplantation.
The quantity of experimentation needed
Due to the unpredictabilities and complexities of treating damaged or traumatized ocular tissue with RKIs (as discussed supra), and the lack of guidance in the instant specification, undue experimentation would be required to practice the claimed methods in their full scope. The art has not demonstrated a method of promoting healing in ocular tissue other than the cornea nor has the art demonstrated fully rehabilitating all types of stressed or damaged ocular tissue to its original state. Given the complexities and variation in treatments used in ophthalmology, non-routine experimentation would be required to determine the healing and rehabilitating effects of RKIs in all ocular tissues for all conditions. Because the instant specification only provides guidance for methods of treating the cornea, specifically methods of reducing corneal edema and improving visual acuity in FCD patients along with methods of conditioning a donor cornea prior to transplantation, undue experimentation would be required to practice claimed methods in their full scope.
Conclusion
Due to the non-routine of experimentation necessary to determine the specific methods of administering RKIs to promote healing or fully rehabilitate stressed or damaged ocular tissue; the lack of direction/guidance presented in the specification regarding the specific requirements for the method; the unpredictability and complexity of the effects of RKIs on different ocular tissues as established by the state of the prior art; the breadth of the claims, undue experimentation would be required of a skilled artisan to make and/or use the claimed invention in its full scope.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
1. Claims 28-41 are rejected under 35 U.S.C. 103 as being unpatentable over US 8,551,974 B1 (Lindstrom, R., 10/08/2013, PTO-892), hereinafter US’974 in view of Okumura, N., et al. (2015), Effect of the Rho Kinase Inhibitor Y-27632 on Corneal Endothelial Wound Healing. Invest. Ophthalmol. Vis. Sci. 56(10):6067-6074 (PTO-892), hereinafter Okumura.
US’974 teaches ophthalmic compositions that include a lubricant, a deturgescent agent, a glycosaminoglycan, and water as well as methods of using the ophthalmic compositions (abstract). Example 1 teaches formulations of the ophthalmic composition wherein amounts are given in weight/volume percent. Formulation Cla-026 comprises 1.0% glycerol; 2.5% chondroitin sulfate; 5.0% dextran; 0.5% boric acid; 0.18% sodium borate; 0.25 sodium chloride; and a balance of purified water (table 1). Sodium borate/boric acid act as a buffer in the formulation to achieve the desired pH (col. 3, lines 56-59), while sodium chloride acts as a tonicity modulating agent (col. 3, lines 18-19). Blind tests were conducted in order to compare the comfort level of the different test formulations (i.e., Cla-026) to the comfort of commercially available lubricant eye drops. The tests were conducted by applying one drop of a test formulation to one eye of a human subject and one drop of the commercially available eye drops in the other eye. This was repeated at 3 time points over a 24 hour period (col. 7-8, lines 22-2). Results are shown in tables II-V. US’974 further claims a method of promoting healing of ocular tissue of a mammal after trauma to such ocular tissue, the method comprising administering to the ocular tissue before, during, or after the trauma an effective amount of an ophthalmic composition comprising: glycerol in a concentration of 1.0%; dextran in a concentration of 5.0%; chondroitin sulfate in a concentration of 2.5%; and water (claims 8-13). The ophthalmic composition further comprises a buffer and a tonicity modulating agent (claim 14). Such a method reads partially on the instantly claimed method of claims 28-34. US’974 also claims a method of fully or partially rehabilitating stressed or damaged ocular tissue to a normal state, the method comprising administering to the stressed or damaged ocular tissue an effective amount of an ophthalmic composition comprising: glycerol in a concentration of 1.0%; dextran in a concentration of 5.0%; chondroitin sulfate in a concentration of 2.5%; and water (claims 15-20). The ophthalmic composition further comprises a buffer and a tonicity modulating agent (claim 21). Such a method reads partially on the instantly claimed method of claims 35-41.
The teachings of US’974 differ from those of the instantly claimed invention in that US’974 fails to disclose a Rho Kinase Inhibitor (RKI) as recited in the instant claims.
Okumura discloses the effects of the Rho Kinase (ROCK) Inhibitor Y-27632 on corneal endothelial wound healing (title). The study methods comprised scraping half the area of the corneal endothelium of rabbits to simulate corneal endothelial damage. A selective ROCK inhibitor, Y-27632 (10 mM), was applied topically for 2 weeks, and then the eye was examined for damage. Additionally, a pilot clinical trial applied Y-27632 eye drops topically to three patients who exhibited severe corneal edema due to corneal endothelial damage (abstract: methods). Results showed that ROCK inhibitor eye drops promote wound healing of severe corneal endothelial damage in a rabbit model by enhancing proliferation of the remaining corneal endothelial cells (CECs). The pilot clinical research study showed that ROCK inhibitor eye drops were considerably effective in patients who exhibited corneal edema after cataract surgery (p. 6068, col. 2, para. 2). Okumura concludes that studied ROCK inhibitor may be developed as an eye drop for treating acute corneal endothelial damage (abstract: conclusions).
It would have been obvious to combine the teachings of US’974 and Okumura before the effective filing date of the claimed invention by incorporating 10 mM of the Y-27632 Rho Kinase Inhibitor of Okumura into the composition used in the methods of US’974 to yield the instantly claimed invention. As discussed above, US’974 teaches methods of promoting the healing of ocular tissue in a mammal after trauma as well as rehabilitating damaged ocular tissue. The methods of US’974 comprise applying an ophthalmic composition such as eye drops to the eye. Okumura similarly teaches methods of promoting the healing of ocular tissue in a mammal after trauma, specifically following corneal endothelial damage in rabbits and humans. The methods of Okumura comprise applying an ophthalmic composition comprising 10 mM Rho Kinase Inhibitor Y-27632 to the eye. Okumura further teaches eye drops. Thus, it would have been obvious to combine the compositions of US’974 and Okumura by incorporating 10 mM of the Y-27632 RKI of Okumura into the ophthalmic composition of US’974 and then using the combined composition in the methods of healing or rehabilitating damaged ocular tissue of US’974. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose…[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Additionally, one of ordinary skill in the art would have been motivated to add 10 mM of the Y-27632 RKI into the composition and methods of US’974 since Okumura teaches 10 mM of this RKI to promote wound healing of severe corneal endothelial damage by enhancing proliferation of the corneal endothelial cells which would be advantageous in a composition used to promote healing and rehabilitation of damaged ocular tissue such as that of US’974. One of ordinary skill in the art would have had a reasonable expectation of success in combining the composition of US’974 and Okumura and using it in the methods of US’974 since both US’974 and Okumura teach eye drops that are applied to the eyes to aid in ocular tissue healing.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 28-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-21 of U.S. Patent No. 8,551,974 in view of Okumura, N., et al. (2015), Effect of the Rho Kinase Inhibitor Y-27632 on Corneal Endothelial Wound Healing. Invest. Ophthalmol. Vis. Sci. 56(10):6067-6074 (PTO-892), hereinafter Okumura. The Obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims and would have been obvious over the reference claims in view of Okumura.
The US’974 claims recite a method of promoting healing of ocular tissue of a mammal after trauma to such ocular tissue, the method comprising administering to the ocular tissue before, during, or after the trauma an effective amount of an ophthalmic composition comprising: glycerol in a concentration of 1.0%; dextran in a concentration of 5.0%; chondroitin sulfate in a concentration of 2.5%; and water (claims 8-13). The ophthalmic composition further comprises a buffer and a tonicity modulating agent (claim 14). Such a method reads partially on the instantly claimed method of claims 28-34. US’974 also claims a method of fully or partially rehabilitating stressed or damaged ocular tissue to a normal state, the method comprising administering to the stressed or damaged ocular tissue an effective amount of an ophthalmic composition comprising: glycerol in a concentration of 1.0%; dextran in a concentration of 5.0%; chondroitin sulfate in a concentration of 2.5%; and water (claims 15-20). The ophthalmic composition further comprises a buffer and a tonicity modulating agent (claim 21). Such a method reads partially on the instantly claimed method of claims 35-41.
The claims of US’974 differ from those of the instantly claimed invention in that US’974 fails to recite a Rho Kinase Inhibitor (RKI).
Okumura discloses the effect of the Rho Kinase Inhibitor Y-27632 on corneal endothelial wound healing (title). The study methods comprised scraping half the area of the corneal endothelium of rabbits to simulate corneal endothelial damage. A selective ROCK inhibitor, Y-27632 (10 mM), was applied topically for 2 weeks, and then the eye was examined for damage. Additionally, a pilot clinical trial applied Y-27632 eye drops topically to three patients who exhibited severe corneal edema due to corneal endothelial damage (abstract: methods). Results showed that ROCK inhibitor eye drops promote wound healing of severe corneal endothelial damage in a rabbit model by enhancing proliferation of the remaining corneal endothelial cells (CECs). The pilot clinical research study showed that ROCK inhibitor eye drops were considerably effective in patients who exhibited corneal edema after cataract surgery (p. 6068, col. 2, para. 2). Okumura concludes that studied ROCK inhibitor may be developed as an eye drop for treating acute corneal endothelial damage (abstract: conclusions).
It would have been obvious to combine the teachings of US’974 and Okumura before the effective filing date of the claimed invention by incorporating 10 mM of the Y-27632 Rho Kinase Inhibitor of Okumura into the composition used in the methods of US’974 to yield the instantly claimed invention. As discussed above, US’974 teaches methods of promoting the healing of ocular tissue in a mammal after trauma. The methods of US’974 comprise applying an ophthalmic composition such as eye drops to the eye. Okumura similarly teaches methods of promoting the healing of ocular tissue in a mammal after trauma, specifically following corneal endothelial damage in rabbits and humans. The methods of Okumura comprise applying an ophthalmic composition comprising 10 mM Rho Kinase Inhibitor Y-27632 to the eye. Okumura further teaches eye drops. Thus, it would have been obvious to combine the compositions of US’974 and Okumura by incorporating 10 mM of the Y-27632 RKI of Okumura into the ophthalmic composition of US’974 and then using the combined composition in the methods of healing or rehabilitating damaged ocular tissue of US’974. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose…[T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Additionally, one of ordinary skill in the art would have been motivated to add 10 mM of the Y-27632 RKI into the composition and methods of US’974 since Okumura teaches 10 mM of this RKI to promote wound healing of severe corneal endothelial damage by enhancing proliferation of the corneal endothelial cells which would be advantageous in a composition used to promote healing and rehabilitation of damaged ocular tissue such as that of US’974. One of ordinary skill in the art would have had a reasonable expectation of success in combining the compositions of US’974 and Okumura and using it in the methods of US’974 since both teach eye drops that are applied to the eyes to aid in ocular tissue healing.
Claims 28-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 12-17 of U.S. Patent No. 9,233,123 in view of Okumura, N., et al. (2015), Effect of the Rho Kinase Inhibitor Y-27632 on Corneal Endothelial Wound Healing. Invest. Ophthalmol. Vis. Sci. 56(10):6067-6074 (PTO-892), hereinafter Okumura. The Obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims and would have been obvious over the reference claims in view of Okumura.
The US’123 claims recite a method of preserving tissue, the method comprising the steps of: providing excised mammalian tissue to be preserved; providing a liquid composition including glycerol in a concentration of 1.0%, dextran in a concentration of 5.0%, chondroitin sulfate in a concentration of 2.5%, and water; and placing the excised mammalian tissue to be preserved into the liquid composition under in vitro conditions (claims 1, 12-17). The excised mammalian tissue to be preserved is ophthalmic tissue (claim 2). It is noted that the instantly claimed methods are not excluded from being performed in in vitro condition, as such the US’123 claims still fall within the scope of the instant intention.
The claims of US’123 differ from those of the instantly claimed invention in that US’123 fails to recite a Rho Kinase Inhibitor (RKI), additionally the US’123 claims do not specify that the method is for “healing” or “rehabilitating” the ocular tissue.
Okumura discloses the effect of the Rho Kinase Inhibitor Y-27632 on corneal endothelial wound healing (title). The study methods comprised scraping half the area of the corneal endothelium of rabbits to simulate corneal endothelial damage. A selective ROCK inhibitor, Y-27632 (10 mM), was applied topically for 2 weeks, and then the eye was examined for damage. Additionally, a pilot clinical trial applied Y-27632 eye drops topically to three patients who exhibited severe corneal edema due to corneal endothelial damage (abstract: methods). Results showed that ROCK inhibitor eye drops promote wound healing of severe corneal endothelial damage in a rabbit model by enhancing proliferation of the remaining corneal endothelial cells (CECs). The pilot clinical research study showed that ROCK inhibitor eye drops were considerably effective in patients who exhibited corneal edema after cataract surgery (p. 6068, col. 2, para. 2). Okumura concludes that studied ROCK inhibitor may be developed as an eye drop for treating acute corneal endothelial damage (abstract: conclusions).
It would have been obvious to combine the teachings of US’123 and Okumura before the effective filing date of the claimed invention by incorporating 10 mM of the Y-27632 Rho Kinase Inhibitor of Okumura into the composition used in the method of US’123 to yield the instantly claimed invention. As discussed above, US’123 teaches a method of preserving ocular tissue of a mammal after trauma (i.e., excision). The methods of US’123 comprise applying an liquid ophthalmic composition to the ocular tissue in vitro. Okumura teaches methods of promoting the healing of ocular tissue in a mammal after trauma, specifically following corneal endothelial damage in rabbits and humans. The methods of Okumura comprise applying an ophthalmic composition comprising 10 mM Rho Kinase Inhibitor Y-27632 to the eye. Thus, it would have been obvious to combine the compositions of US’123 and Okumura by incorporating 10 mM of the Y-27632 RKI of Okumura into the liquid ophthalmic composition of US’123 and then using the combined composition in the method of applying the composition to ophthalmic tissue following trauma as recited by US’123. It is generally considered prima facie obvious to combine prior art elements according to known methods to yield predictable results. Additionally, one of ordinary skill in the art would have been motivated to add 10 mM of the Y-27632 RKI into the composition and methods of US’123 since Okumura teaches 10 mM of this RKI to promote wound healing of severe corneal endothelial damage by enhancing proliferation of the corneal endothelial cells which would be advantageous in a composition used to preserve ocular tissue such as that of US’123. One of ordinary skill in the art would have had a reasonable expectation of success in combining the compositions of US’123 and Okumura and using it in the methods of US’123 since both teach liquid ophthalmic compositions that are applied to the eyes to benefit the ocular tissue in some way. The ability of the combined composition to “heal” or “rehabilitate” the ocular tissue to which it is applied is an inherent property of the composition. Since the composition made obvious by the prior art is identical to the composition claimed, the composition must necessarily have the characteristics claimed as an inherent property. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter, which there is reason to believe inherently includes functions that are newly cited, or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference.
Claims 28-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 7,820,639 in view of Okumura, N., et al. (2015), Effect of the Rho Kinase Inhibitor Y-27632 on Corneal Endothelial Wound Healing. Invest. Ophthalmol. Vis. Sci. 56(10):6067-6074 (PTO-892), hereinafter Okumura. The Obviousness Double Patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims and would have been obvious over the reference claims in view of Okumura.
The US’638 claims recite an ophthalmic composition consisting essentially of: glycerol in a concentration of 0.1%; dextran in a concentration of 5.0%; chondroitin sulfate in a concentration of 2.5%; and water (claims 1-6).
The claims of US’638 differ from those of the instantly claimed invention in that US’638 does not claim a method of using the ophthalmic composition for healing or rehabilitating ocular tissue nor does US’638 recite a Rho Kinase Inhibitor (RKI)
Okumura discloses the effect of the Rho Kinase Inhibitor Y-27632 on corneal endothelial wound healing (title). The study methods comprised scraping half the area of the corneal endothelium of rabbits to simulate corneal endothelial damage. A selective ROCK inhibitor, Y-27632 (10 mM), was applied topically for 2 weeks, and then the eye was examined for damage. Additionally, a pilot clinical trial applied Y-27632 eye drops topically to three patients who exhibited severe corneal edema due to corneal endothelial damage (abstract: methods). Results showed that ROCK inhibitor eye drops promote wound healing of severe corneal endothelial damage in a rabbit model by enhancing proliferation of the remaining corneal endothelial cells (CECs). The pilot clinical research study showed that ROCK inhibitor eye drops were considerably effective in patients who exhibited corneal edema after cataract surgery (p. 6068, col. 2, para. 2). Okumura concludes that studied ROCK inhibitor may be developed as an eye drop for treating acute corneal endothelial damage (abstract: conclusions).
It would have been obvious to combine the teachings of US’638 and Okumura before the effective filing date of the claimed invention by incorporating 10 mM of the Y-27632 Rho Kinase Inhibitor of Okumura into the composition of US’638 and then use it in the method of Okumura to yield the instantly claimed invention. It is generally considered prima facie obvious to combine prior art elements according to known methods to yield predictable results. Additionally, one of ordinary skill in the art would have been motivated to add 10 mM of the Y-27632 RKI into the composition of US’638 since Okumura teaches 10 mM of this RKI to promote wound healing of severe corneal endothelial damage by enhancing proliferation of the corneal endothelial cells which would be advantageous in an ophthalmic composition such as that of US’638. It would have been further obvious to use the combine composition in the method of Okumura for promoting the healing of ocular tissue in a mammal after trauma, specifically following corneal endothelial damage in rabbits and humans. The methods of Okumura comprise applying an ophthalmic composition comprising 10 mM Rho Kinase Inhibitor Y-27632 to the eye. One of ordinary skill in the art would have had a reasonable expectation of success in combining the compositions of US’638 and Okumura and using it in the methods of US’638 since both teach ophthalmic compositions. The ability of the combined composition to “heal” or “rehabilitate” the ocular tissue to which it is applied is an inherent property of the composition. Since the composition made obvious by the prior art is identical to the composition claimed, the composition must necessarily have the characteristics claimed as an inherent property. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter, which there is reason to believe inherently includes functions that are newly cited, or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference.
Conclusion
No claims are allowed.
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/SUSANNAH S ARMSTRONG/Examiner, Art Unit 1616
/Mina Haghighatian/Primary Examiner, Art Unit 1616