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/Restrictions
Applicant's election with traverse of Group II, claim 10, drawn to a method of making a product; and the species corresponding to IX Preparation Method in the reply filed on December 15, 2025 is acknowledged. The traversal is on the ground(s) that the method of making a product claim is not materially different in scope and that there is no search burden to examine all of the claims together. This is not found persuasive because the test for distinct inventions is whether the product, method of making the product as claimed can be used in a materially different process. The product and method of treating require different search strategies than the method of making the product. In the instant case, the product could be used in treating diseases from lacrimal dysfunction syndrome with gastroesophageal reflux disease, dry eye syndrome, or another disease or symptom, which is different than the method of making the product of Group II.
The requirement is still deemed proper and is therefore made FINAL.
The species of method of group II, therefore claims 10 and 18-24 which read on the elected species has been considered.
Claims 1-9 and 11-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 15, 2025.
Status of Claims
Claims 1-13 and 18-24 are pending. Claims 1-9 and 11-13 are withdrawn from further consideration. Claims 10 and 18-24 are under examination.
Priority
This application is a 371 National Phase of International Application NO. PCT/IB2021/054572, filed on 05/26/2021, and claims foreign priority to Italian Application No. 102020000012370 filed on 05/26/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 16, 2022 complies with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The information disclosure statement filed May 13, 2025 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because a copy of JP 2004537970 has not been provided. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Claim Objections
Claim 22 is objected to because of the following informalities: the word “the” is missing before “alcoholic solution” in the second line. Appropriate correction is required.
Claim 23 is objected to because of the following informalities: is grammatically incorrect. It is suggested to amend line 2, “application the eye” to “application to the eye”.. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 10 is 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 indefinite language is: “dissolving pepstatin in a solvent, at neutral pH to obtain an alcoholic solution of pepstatin, followed by diluting the alcoholic solution in an aqueous solution”.
The language is indefinite because it is not clear whether the “solvent” is alcohol or comprising a solution containing alcohol. In addition, it is not clear how alcoholic solution is obtained, if it is due to addition of more alcohol. Therefore the term “solvent” in claim 10 is a relative term which renders the claim indefinite. Appropriate definite claim limitation regarding the solvent is required.
Claims 18-24 which depend on claim 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as these claims incorporate by dependency the indefiniteness of claim 10.
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.
Claims 10, 18, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2008/039984 (published 04/03/2008, on IDS filed 11/16/2022) in view of WO 1994/24150 (published 10/27/1994).
WO’984 teaches that pepstatin is a powerful inhibitor of aspartyl proteases including pepsin (see [0005]). WO’984 identifies that pepstatin can be utilized to treat diseases and disorders related to aspartyl proteases (see [0004]), and could be formulated with pharmaceutical excipients to form pepstatin-containing eye drops (see [0033], [0043], [0045]).
It is already known art that pepstatin A is a low molecular weight inhibitor of aspartyl proteases, including pepsin, cathepsin D, renin, etc. WO’984 teaches the composition of containing cathepsin D inhibitor is pepstatin A or a salt (see Claim 2). WO’984 discloses a process for preparing medicinal products which can be used in the treatment of cathepsin D-related conditions, consisting in mixing pepstatin or the pharmaceutically acceptable salts of this compound with one or more compatible and pharmaceutically acceptable diluents and/or adjuvants (page 10, [0052]). WO’984 further specifies that for liquid compositions, pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elixirs may be used, containing inert diluents such as water, ethanol (see [0048]). WO’984 discloses mixtures of pepstatin A were made by creating a 5 mM solution of pepstatin A in 95% ethanol (e.g. an alcoholic solution of pepstatin at a neutral pH) (see Example 1, [0062]).
WO’984 do not teach specifically about the aqueous solution composition comprising alginic acid salt.
WO’150 comprise invention in the field of pepstatin analog proteinase inhibitors, more particularly proteinase inhibitors for use in the treatment and prevention of infections in plants and animals (see page 1, line 9-13). WO’150 teaches the proteinase inhibitors may be applied as a suspension or dispersion, e. g. as an aqueous suspension with a suitable protectant such as alginate, magnesium silicate, etc (see page 23, line 5-9).
At the time before the effective filing date of the claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to combine the mixture comprising of pepstatin and alginic acid or a salt derivative in an aqueous composition as taught by WO’150 with an alcoholic solution containing pepstatin as taught by WO’984 to arrive at the presently claimed invention. The artisan of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because it would predictably lead to a combined product having the same predicted and expected utility, namely eye drops usable to further reduce pepsin in the eye following administration as eye drops. It is prima facie obvious to substitute equivalents known in the art for the same purpose. MPEP §2144.06.
Regarding claim 10, US’984 teaches that the medicinal products consist at least of pepstatin, in free form or in the form of an addition salt with a pharmaceutically acceptable acid, in the pure state or in the form of a composition in which it is combined with any other pharmaceutically compatible product, which may be inert or physiologically active. The medicinal products according to the invention may be employed orally, cutaneously, transdermally, nasally, as eye drops (see page 8, [0045]). US’984 further specifies for sterile compositions administration, preferably be solutions, aqueous or non-aqueous, suspensions or emulsions, as a solvent or vehicle, water, alcohols, etc. may be employed (see [0049] and [0050]).
Regarding claims 18 and 19, WO’984 teaches the solutions were diluted to 150 mM for use in efficacy studies (see Example 1, [0062]). At the time before the effective filling date of the claimed invention, it would have been obvious to use solvent as ethanol and as specified “expected amount of pepstatin in the composition: less than or equal to 1 pM” because the claimed range overlaps with and within the range disclosed by WO’984.
Claims 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2008/039984 (published 04/03/2008, on IDS filed 11/16/2022) in view of WO 1994/24150 (published 10/27/1994) as applied to claims 10, 18, and 19, above, and in further view of US 8,501,822 (published 08/06/2013).
The teachings of WO’984 and WO’150 are discussed above. WO’984 and WO’150 do not teach specifically about the use of hyaluronic acid or a pharmaceutically acceptable salt and the formulation for diluted solution as eye drops as claimed.
US’822 teaches the ophthalmic composition contains alginic acid and/or a salt in combination with hyaluronic acid and/or a salt (see Abstract). US’822 teaches in the ophthalmic composition, a single type of alginic acid and salts may be used, or any combination of two or more types may be used. (see page 7, col 7, line 35-36). US’822 teaches the ophthalmic composition also comprises at least one member selected from the group consisting of hyaluronic acid and salts (see page 7, col 7, line 64-67). US’822 specifies examples of the hyaluronic acid salt include salts with an alkali metal, such as sodium or potassium; salts with an alkaline earth metal, such as calcium or magnesium; and salts with a metal (see page 7, col 8, line 32-35). US’822 teaches the pH of the ophthalmic composition is not particularly limited, so long as it is within a pharmacologically or physiologically acceptable range; more preferably from 6 to 8 (see page 8, col 10, line 11-16; see neutral pH conditions in Test Examples 1 and 3; Tables 1, 3, 8, and 9). US’822 discloses the ophthalmic composition is in a liquid or gel form, and preferably is in a liquid form. Preferable embodiment of the ophthalmic composition is an aqueous ophthalmic composition (see page 8, col 10, line 1-6). US’822 further teach the ophthalmic composition is an eye drop, an eye wash, or a wetting and rewetting drop (see page 5, col 3, line 16-18).
At the time before the effective filing date of the claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to use the formulation at neutral pH specifically for use as eye drops taught by WO’822 in diluted alcoholic solution containing pepstatin as taught by WO’984 to arrive at the presently claimed invention. The artisan of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because it would predictably lead to a combined product having the same predicted and expected utility, namely eye drops usable to further reduce pepsin in the eye following administration as eye drops. It is prima facie obvious to substitute equivalents known in the art for the same purpose. MPEP §2144.06.
Regarding claim 22, US’822 teaches the ophthalmic composition of the invention exhibits a longer retention of mixed components, such as hyaluronic acid and/or a salt thereof, and other pharmacologically active ingredients, on an ocular mucosa (page 6, col 6, line 23-27). US’822 specifies in order to prepare the ophthalmic composition in a desired form, various components and additives can be appropriately selected and mixed singly or in any combination in the ophthalmic composition by a conventional method, as long as the effects of the present invention are not impaired. As the component and the additive, various additives are pharmaceutical excipients (page 9, col 11, line 27-34).
Regarding claims 23 and 24, US’822 teach about the ophthalmic composition of the invention is used in the form of an eye drop, an eye wash, a wetting and rewetting drop (page 9, col 11, line 46-49).
Therefore, the presently claimed invention was prima facie obvious to one of ordinary skill in the art at the time of the effective filling date.
Claims 20 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2008/039984 (published 04/03/2008, on IDS filed 11/16/2022) in view of WO 1994/24150 (published 10/27/1994), as applied to claims 10, 18, and 19above, and in further view of WO 2018/215897 (published 11/29/2018).
The teachings of WO’984 and WO’150 are discussed above. WO’984 and WO’150 do not teach about using alginate salt is magnesium alginate as claimed.
WO’897 teaches the use of alginate salt, more preferably magnesium alginate in the composition (see Claim 8). WO’897 specifies ophthalmic solution comprises, component % by weight/total weight - Magnesium alginate (see Experimental section, and Compositions on pages 11-13). It would have been prima facie obvious to combine the teachings of US’897 with WO’984 and WO’150 before the effective filling date of the claimed invention by considering use of magnesium alginate as a stable component in the aqueous medium to arrive at the instantly claimed invention. One of ordinary skill in the art would have been motivated to utilize magnesium alginate to produce improved ophthalmic grade eye drops as taught in WO’897.
Therefore, the presently claimed invention was prima facie obvious to one of ordinary skill in the art at the time of the effective filling date
Conclusion
No claim is allowed.
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/KOYELI BANERJEE/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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