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 .
Response to Amendment
The amendment received on 11/02/2025 is acknowledged. Claims 1, 3 and 5 have been amended. Claims 1, 3, 5, 7 and 9-17 are currently pending and have been treated on the merits.
Response to Arguments
Applicant’s arguments received on 11/02/2026 have been fully considered, but they are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that Langston does note teach that ribonucleases may be used to treat viral infections. This argument is not persuasive as Langston is not used to teach the use of ribonucleases such as ranpirnase to treat viral infection, the primary reference Saxena discloses the use of these enzymes as antiviral. Applicant argues that Langston does not provide a teaching suggestion or motivation of using ribonuclease to treat infection; however, Langston is not used to provide a teaching suggestion or motivation of using ribonuclease to treat infection, nor is an explicit teaching suggestion or motivation required to be present in the prior art references. The motivation to combine references has been provided in the rejection statement.
Applicant argues that Jain teaches that anti-viral compounds may be added to the composition for the eye and does not teach the use of ranpirnase as an anti-viral compound. This argument is not persuasive as Jain is not used to teach ranpirnase as an anti-viral treatment, the primary reference Saxena discloses the anti-viral properties of ranpirnase.
Applicant argues that they expected ranpirnase to be inflammatory to the eye based on the concept that proteins in general are known to be highly irritating to the eyes. This argument however is not found persuasive as the use of the enzyme ranpirnase is known to be used for treatment in the eye as taught by Jain. Further Jain teaches inflammation of the eye is one of the symptoms of the disorders in Jain being treated ([0079]-[0089]). The ability of ranpirnase to be applied to the eye is thus disclosed in the art and that it may be non-irritating to the eyes is not unexpected or in the alternate is an inherent product of the enzyme formulated for ophthalmic application.
Applicant argues that when a proprietary aqueous solution is used to apply the enzyme to the eye it is non-irritating, and argues that this was a surprising and remarkable result. No evidence has been presented which suggest that an ophthalmic composition comprising ranpirnase is irritating to the eye. However, it is noted that the specification provides no description of the “proprietary” vehicle. If the vehicle is critical for the formulation of a non-irritating composition, adequate written description must be provided to enable one of ordinary skill to make and use 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claim 1, 3, 5, 7, 9-17 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Saxena (USPGPub 20120121569/IDS submitted) in view of each of Langston (“Herpes Simplex Virus in the Eye”, Digital Journal of Ophthalmology, Oct 2002/IDS submitted) and Jain (WO 2013089835/IDS submitted) as evidenced by Sambrook (“Herpes Simplex Eye Infections” HSV Information, Patient, 2014, available at https://patient.info/doctor/herpes-simplex-eye-infections, /previously cited).
Regarding claims 1, 5 and 9, and the limitations “A method of treating a herpesviral infection of a human eye in an individual, comprising the step of administering to a surface of a conjunctiva or the eye of the individual a composition comprising a therapeutically effective dose of one or more ranpirnases and a pharmaceutically-acceptable vehicle, wherein the composition comprises about 0.1% v/v ranpirnase”, “A method for treating a herpesviral infection of the human eye in the individual, the method comprising administering an ophthalmic composition comprising about 0.1% v/v ranpirnase to a surface of a conjunctiva or the eye of the individual, the composition comprising: a. a therapeutically effective dose of a one or more ranpirnases that is non-irritating to the eye; and b. a vehicle.” and “A method of treating a herpesviral infection of a human eye of an individual, the method comprising the step of topically administering to a surface of a conjunctiva or the eye of the individual, a composition comprising a therapeutically effective amount of a ranpirnase wherein the composition comprises about 0.1% ranpirnase.”, Saxena teaches that viral infections caused by Herpes simplex virus can be treated using Ribonuclease A’s, such as ranpirnase, ‘805 variant, and rAmphinase2, (Claim 8). Saxena further teaches the use of the RNAseA to treat other human herpesviridiae infections in humans (Claims 1-4 and [0001]-[0004]). Saxena teaches the viral infections are human and the enzymes well tolerated by humans ([0001]-[0004]), one of ordinary skill in the art would thus find it obvious that the intended patient is human.
Saxena does not teach that the viral infection can be in the eye nor does Saxena teach that the ribonuclease A can be administered directly to the eye. These differences however would have been obvious to one of ordinary skill in the art as the infection of the eye by Herpes Simplex Virus is known in the art as taught by Langston, and further the administration of Ribonuclease A to the eye for treatment of viral infections is known in the art as taught by Jain.
In the same field of endeavor as Herpes Simplex infections, Langston teaches Herpes Simplex Virus can infect the eye, “Occasionally, the virus does reactivate (stress!) and, instead of traveling back down the nerves to the mouth or nose, it goes to the eye causing the illness there. (Page 1)”.
In the same field of endeavor as treating viral infections with Ribonuclease A, Jain teaches a method of treating eyes for conditions including viral infection by administering nucleases and teaches the use of Ribonuclease A, ([0072], [0007]). Jain further teaches that the Ribonuclease A can be formulated for ophthalmic delivery through use of carriers or vehicles and stabilizers as well as buffers, wetting agents, antioxidants, tonicity adjusters, and steroids ([0040], [0050]-[0052], claims 7 and 8).
One of ordinary skill in the art would have found it obvious that Herpes Simplex virus could be treated using ranpirnase, ‘805 variant and rAmphinase 2 as Saxena teaches these as effective antiviral agents for the virus. One of ordinary skill in the art would have found it obvious that these enzymes could be administered to the eye as the infection of this virus is known to occur there as taught by Langston, and Ribonuclease A is known in the art to be used to treat ocular viral infections as taught by Jain. One of ordinary skill in the art would further have a reasonable expectation in doing so as Jain teaches the administration of Ribonuclease A to the eye for the treatment of viral infections.
Regarding claims 1, 5, and 9 and the limitation “administering an ophthalmic composition to a surface of a conjunctiva or the eye of the individual” Saxena teaches formulation for topical administration to the eye or ocular tissue ([0050]), such administration will result in administering of the composition to the conjunctive or the eye.
Regarding claims 1, 5, and 9 and the limitation “wherein the composition comprises about 0.1% ranpirnase” Jain teaches that dosages may be readily determined without undue experimentation ([0039]).
Further As noted in the instant specification, (Page 9 Ln 20-Page 11 of instant specification), determination of a therapeutically effective dosage is within the ability of one of ordinary skill in the art and can be determined by routine experimentation.
One of ordinary skill in the art would find it obvious to determine therapeutically effective dose via routine administration and arrive at the administration of a composition comprising 0.1% v/v ranpirnase.
Regarding claims 1, 5 and 9 and the limitation “human eye”, Saxena teaches the viral infections are human and the enzymes well tolerated by humans ([0001]-[0004]), one of ordinary skill in the art would thus find it obvious that the intended patient is human.
Regarding claims 1, 3 and 5 and claims dependent thereon the limitations of “wherein administering the composition is non-irritating to the eye.”, “administrating the composition is non-irritating to the eye as determined by a Draize test”, and “the composition comprising:a. a therapeutically effective dose of one or more ranpirnases; and b. a vehicle,wherein administering the ophthalmic composition does not cause an inflammatory response in the eye.”, Jain further teaches that the Ribonuclease A can be formulated for ophthalmic delivery through use of carriers and stabilizers as well as buffers, wetting agents, antioxidants, tonicity adjusters, and steroids ([0040], [0050]-[0052], claims 7 and 8), i.e. vehicle. One of ordinary skill in the art in formulating the ophthalmic composition would find it obvious to create a non-irritating non inflammatory composition so that the medicine administered would not irritate the infected eye it is treating. One would be motivated to do so to create a composition which was comfortable for the patient to use. Further one of ordinary skill in the art would have a reasonable expectation of success in doing so as Jain teaches various components which can be used in making the composition for ophthalmic administration.
Regarding claim 7, and 14-17 and the limitations “wherein the vehicle is an aqueous solution”, “wherein the ranpirnase is formulated as an ophthalmic pharmaceutical composition”, “wherein the ophthalmic pharmaceutical composition is a solution, a suspension, a nanosuspension, an emulsion, a microemulsion, a nanoemulsion, an ointment, a gel, a hydrogel, liposomes, niosomes, nanoparticles, or dendrimers”, “wherein the ophthalmic pharmaceutical composition further comprises a pharmaceutically acceptable carrier and/or a pharmaceutically acceptable excipient”, and “wherein the ranpirnase is administered as eye drops”, Jain teaches the compositions of ribonuclease administered may be formulated as eye drops using suitable pharmaceutical ophthalmic carriers such as aqueous solution ([0039]. [0051]).
Regarding claims 10 and the limitations “wherein the ranpirnase is a recombinant ranpirnase”, Applicant claims a product by process. A product by process is limited only to the structure implied by the steps, and not to the manipulations recited in the steps, See MPEP 2113, "The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979) “. The structure of the enzyme remains the same whether regardless of the source, and thus being recombinant does not add a further structure to the enzyme.
Alternatively, Saxena teaches the recombinant production of Amphinase-2 (Abstract, [0001]-[0004]), one of ordinary skill in the art would therefore find it obvious that the ranpirnase could be produced by recombinant methods as well. One ordinary in the art would further have a reasonable expectation of success in doing so as Saxena teaches a similar enzyme is produced by recombinant methods.
Regarding claim 11 and the limitation “wherein the ranpirnase is SEQ ID NO: 1 or SEQ ID NO: 2”, The instant application notes that SEQ ID 1 and 2 correspond to ranpirnase and the ‘805 variant “The amino acid sequence of ranpirnase is provided in SEQ ID NO: 1.…The amino acid sequence of the '805 variant is provided in SEQ ID NO:2.”, Saxena teaches the use of these enzyme (Claims 8, [0001]-[0008]).
Regarding claim 12 and the limitation “wherein the herpesviral infection is the cause of chorioretinitis, viral keratitis, viral conjunctivitis, or cytomegalovirus retinitis”, Langston teaches teaches that herpes virus simplex can infect the eye. As evidenced by Sambrook, Herpes Simplex Eye infections can cause conjunctivitis, keratitis and retinitis (Page 2). Thus the method of Saxena, Langston and Jain result in the treatment of herpesviral infections that cause keratitis, retinitis, and conjunctivitis.
Regarding claim 13 and the limitation “type I Herpes simplex virus, human cytomegalovirus, or Herpes zoster virus”, Saxena teaches the treatment of Herpes simplex virus, (Claim 8, [0001-]-[0004]). Saxena further teaches the use of the enzymes to treat other human Herpesviridae including and human cytomegalovirus (Claims 1-4, [0001]-[0004]).
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 CHARLES Z CONSTANTINE whose telephone number is (571)270-5533. The examiner can normally be reached Mon-Fri 9-5.
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/CHARLES Z CONSTANTINE/ Examiner, Art Unit 1657
/ROBERT J YAMASAKI/ Primary Examiner, Art Unit 1657