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 .
Non-Final Rejection
The Status of Claims:
Claims 1-20 are pending.
Claims 1-20 are rejected.
DETAILED ACTION
1. Claims 1-20 are under consideration in this Office Action.
Priority
2. It is noted that this application is a 371 of PCT/CN2022/095155 05/26/2022 , which has a foreign priority document, CHINA CN202110614105.6 06/02/2021.
Drawings
3. None.
IDS
4. The IDS filed on 9/26/25, 7/8/25, 1/22/25, 12/15/23 are reviewed by the
examiner.
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 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.
Specification
The title of the invention is not descriptive.
The use of the term “ the prevention “in the title is inconsistent with what is described in the specification and there is a rejection under the first paragraph of 35 U.S.C. 112(a).
Abstract
The abstract of the disclosure is objected to because of the presence of the term” the prevention” in the abstract . the examiner recommends to remove the term” the prevention” from the abstract.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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 16 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.
Claim 16 provides for instructions for use, but, since the claim does not set forth any steps involved in the method/process, it is unclear whatmethod/process applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
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.
Claims 1-20 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for treating specific diseases, does not reasonably provide enablement for preventing an ophthalmic disease in a subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. Applicants are not enabled for preventing any of the ophthalmic diseases. The only established prophylactics are vaccines not the claimed drug such as present here. In addition, it is presumed that “prevention” of the claimed diseases would require a method of identifying those individuals who will develop the claimed diseases before they exhibit symptoms. There is no evidence of record that would guide the skilled clinician to identify those who have the potential of becoming afflicted.
“The factors to be considered [in making an enablement rejection] have been summarized as the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art, and the breadth of the claims”, In re Rainer, 146 USPQ 218 (1965); In re Colianni, 195 USPQ 150, Ex parte Formal, 230 USPQ 546. 1) As discussed above, preventing diseases requires identifying those patients who will acquire the disease before any ophthalmic disease occurs. This would require extensive and potentially opened ended clinical research on healthy subjects. 2) There is no working example of such a preventive procedure in man or animal in the specification. 3) The claims rejected are drawn to clinical preventative medicine and are therefore physiological in nature. 4) The state of the art is that no general procedure is art-recognized for determining which patients generally will become the patients with the ophthalmic disease before the fact. 6) The artisan using Applicants invention would be a Board Certified physician in the ophthalmic disease with an MD degree and several years of experience. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting a compound to be effective for the prevention of the ophthalmic disease in the subject generally. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable to any agent to be able to prevent ophthalmic diseases generally. That is, the skill is so low that no compound effective generally against the ophthalmic disease has ever been found let alone one that can prevent such conditions. 7) It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved", and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed diseases.
The Examiner suggests deletion of the word “preventing” from the claims.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1,3, 5, 9, 17-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated clearly by Yu (Study on Atropine Cyclodextrin Eye Drops for Inhibiting Myopia Development, Hebei University of Science and Technology, May, 2019, p.1-65).
Yu discloses an atropine y cyclodextrin eye drop composition for treating myopia contains 1.0% atropine, 18% y cyclodextrin, 0.05 mol/L of phosphate buffer (1.79%), and 1.0% polyvinyl alcohol. The main process parameters include: stirring time 16 h, stirring rate 500 r/min, and preparation of inclusion complex powder using freeze drying method (a lyophilized preparation); by comparing the atropine y cyclodextrin eye drop and atropine sulfate solution in terms of targeting index, targeting efficiency, peak concentration ratio and other indexes, it is concluded that the atropine y cyclodextrin eye drop changes distribution of atropine in eye tissue and has a certain sclera targeting effect(see abstract page ). These are identical with the claims.
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 1-2, 4, 6-16, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Yu (Study on Atropine Cyclodextrin Eye Drops for Inhibiting Myopia Development, Hebei University of Science and Technology, May, 2019, p.1-65) in view of Quan Chunman (CN 112426405) and Liu et al (CN110934869A).
Applicant claims the followings:
1. (Currently Amended) An eye drop composition for preventing or treating an ophthalmic disease, comprising: (a) a lyophilized preparation comprising atropine or a pharmaceutically acceptable salt thereof the atropine; and (b) a reconstitution diluent, wherein the lyophilized preparation and the reconstitution diluent are separated.
2. (Currently Amended) The eye drop composition of claim 1, wherein the pharmaceutically acceptable salt of the atropine is atropine sulfate.
4. (Original) The eye drop composition of claim 1, wherein a pH of the eye drop composition is in a range from 5.0 to 6.4.
6. (Currently Amended) The eye drop composition of claim 5, wherein the buffer salt system is selected from one or more of a citrate buffer system and a phosphate buffer system, and a concentration of the buffer salt system is from 0.01% to 1%.
7. (Currently Amended) The eye drop composition of claim 5, wherein the matrix agent is 28 selected from one or more of mannitol, sorbitol, sodium chloride, and sucrose,; and a concentration of the matrix agent is from 1% to 4%.
8. (Currently Amended) The eye drop composition of claim 5, wherein the stabilizer is selected from one or more of sorbitol and mannitol, a concentration of the stabilizer is from 0.05% to 1%.
9. (Currently Amended) The eye drop composition of claim 1, wherein the reconstitution diluent comprises one or more selected from the group consisting of a buffer salt system, an osmotic pressure regulator, a chelating agent, and a bacteriostatic agent.
10. (Currently Amended) The eye drop composition of claim 9, wherein the buffer salt system is selected from one or more of purified water, a phosphate buffer systems and a citrate buffer system, a concentration of the buffer salt system is from 0.01% to 1%.
11. (Currently Amended) The eye drop composition of claim 9, wherein the osmotic pressure regulator is selected from one or more of mannitol, sodium chloride, glucose, phosphate buffer, and borax, and, a concentration of the osmotic pressure regulator is from 1% to 4%.
12. (Currently Amended) The eye drop composition of claim 9, wherein the chelating agent is disodium edetate, and a concentration of the chelating agent is from 0.01% to 0.03%.
13. (Currently Amended) The eye drop composition of claim 9, wherein the bacteriostatic agent is selected from one or more of benzalkonium chloride, ethylparaben, benzalkonium bromide, and polyquaternium-1, a concentration of the bacteriostatic agent is from 0.005% to 0.1%.
14. (Currently Amended) A method for preparing the eye drop composition of any one of claim 1,comprising steps of:(a) contacting the a buffer salt system in the lyophilized preparation with the atropine or the pharmaceutically acceptable salt thereof the atropine, and optionally, one or more of a matrix agent and a stabilizer, and lyophilizing to obtain the lyophilized preparation; and (b) contacting the a buffer salt system in the reconstitution diluent optionally with one or more of an osmotic pressure regulator, a chelating agent, and a bacteriostatic agent optionally to obtain the reconstitution diluent.
15. (Currently Amended) The method of claim 14, wherein the step (a) and the step (b) each independently comprise: adjusting a pH of a mixed solution to a range from 5.0 to 6.4 after the contacting is completed.
16. (Currently Amended) A kit for preventing or treating an ophthalmic disease, comprising: (a) a lyophilized preparation comprising atropine or a pharmaceutically acceptable salt thereof the atropine;(b) a reconstitution diluent; and optionally, (c) instructions for use, wherein the lyophilized preparation and the reconstitution diluent are separated.
19. (New) The eye drop composition of claim 3, wherein the concentration of the atropine or the pharmaceutically acceptable salt of the atropine is in the range from 0.01% to 0.5%.
20. (New) The eye drop composition of claim 19, wherein the concentration of the atropine or the pharmaceutically acceptable salt of the atropine is in the range from 0.01% to 0.08%.
Determination of the scope and content of the prior art
Yu (Study on Atropine Cyclodextrin Eye Drops for Inhibiting Myopia Development, Hebei University of Science and Technology, May, 2019, p.1-65).
Yu discloses an atropine y cyclodextrin eye drop composition for treating myopia contains 1.0% atropine, ,18% y cyclodextrin, 0.05 mol/L of phosphate buffer as in claims 5 & 9-10 (1.79%), and 1.0% polyvinyl alcohol. The main process parameters include: stirring time 16 h, stirring rate 500 r/min, and preparation of inclusion complex powder using freeze drying method(a lyophilized preparation) as in claim 1; by comparing the atropine y cyclodextrin eye drop and atropine sulfate solution in terms of targeting index, targeting efficiency, peak concentration ratio and other indexes, it is concluded that the atropine y cyclodextrin eye drop changes distribution of atropine in eye tissue and has a certain sclera targeting effect(see abstract page ).
The current invention, however, differs from the prior art in that the use of atropine sulfate in the claimed composition, a kit containing a lyophilized preparation comprising atropine and a pH of the eye drop composition, the concentration of the buffer salt system, the matrix agent, the chelating agent , the bacteriostatic agent are unspecified in the prior art.
Quan Chunman discloses a pharmaceutical composition for treating myopia development, eye drops, and a preparation method and the eye drops are composed of the following components, by w/v, 0.001%-2% of atropine drugs such as atropine sulfate as in claim 2 (see page 14, example 1 , a paragraph#0053) , 0%-2% of a thickening agent, an acid-base regulator, an osmotic pressure buffer agent such as sodium chloride , mannitol as in claims 7-8, 11 (page 11 , a paragraph#0037), 0%-2.2% of a stabilizer as in claim 12 (partially), 0%-0.05% of a bacteriostatic agent, such as benzalkonium chloride, benzalkonium bromide or ethylparaben as in claim 13 (see pages 12-13 , a paragraph#0044 & 0047) and the balance of water, the pH value of the pharmaceutical composition is 3.0-8.5, as in claims 4 and 15 wherein the stabilizer is selected from one or more of sodium pyrosulfite, sodium hydrogen sulfite, sodium sulfite, sodium thiosulfate, thiourea, vitamin C, cysteine or hydrochloride thereof, citric acid and tartaric acid. The eye drops can effectively treat and delay juvenile myopia (see abstract).
It provides a method for preparing the eye drops, comprising the following steps:
After completely dissolving the stabilizer, thickener, pH adjuster, antibacterial agent, and osmotic buffer in water, add the atropine-like drug, dissolve it evenly, and then filter it to obtain the final product as in claim 14. Alternatively, after completely dissolving atropine-like drugs in water, add a solution of
stabilizer, thickener, acid-base regulator, antibacterial agent, and osmotic buffer, mix well, and filter to obtain the final product. (see page 13, paragraphs#0049-0050)
Furthermore, Liu et al teaches an atropine pharmaceutical composition containing atropine sulfate for treating NITM (near work-induced transient myopia) (see (page 12, paragraphs#0054-0055) and its kit product which is a medicine box product comprising a drug and a product instruction manual (see page 14, a paragraph#0063).
Specifically, the pharmaceutical composition is an ophthalmic pharmaceutical composition by an ophthalmic preparation such as eye drops (see page 7, a paragraph#0019). Furthermore, the pharmaceutical composition contains 0.001-0.2% of atropine or pharmaceutical salts of atropine and one or more pharmaceutically acceptable ingredients, for example, a pH regulator , an osmotic pressure regulator, a preservative , and/or a stabilizer wherein the pH value of the pharmaceutical composition is 4.0-6.5, and the pH regulator is any one or more which are selected from sodium dihydrogen phosphate, disodium hydrogen phosphate, citric acid, citrate, boric acid and borate. Osmotic pressure regulators, such as any one or more selected from glycerol, mannitol, propylene glycol, sodium chloride, and potassium chloride (see page 9, a pargraph#0028); preservatives, such as any one or more selected from benzalkonium chloride, parabens, and polyquaternium salts(see page 10, a pargraph#0029); In addition, a stabilizer or chelating agent is selected from disodium edetate as in claims 8 &12 (partially) (see page 10, a paragraph#0030)
For experimental drugs, 0.01% atropine sulfate eye drops as in claims 19 and 20 were prepared using 0.9% sodium chloride solution, and the pH was adjusted to 4.0, 4.5, 5.0, 5.5, 6.0, and 6.5 with hydrochloric acid, respectively (see page 36 ,a paragraph#0163).
Ascertainment of the difference between the prior art and the claims
The difference between the instant application and the applied Yu art is that the Yu does not expressly teach the use of atropine sulfate in the claimed composition, a kit prepared by means of a lyophilization method comprising atropine and a pH of the eye drop composition, the concentration of the buffer salt system, the matrix agent, the chelating agent, the bacteriostatic agent
The deficiencies of the Yu are cured by the Quan Chunman and Liu et al.
The difference between the instant application and the applied Quan Chunman art is that the Quan Chunman does not expressly teach a lyophilized preparation comprising atropine and a kit product obtained by means of using a lyophilized preparation comprising atropine and the name of the chelating agent. The deficiencies of the Quan Chunman are cured by the Yu and Liu et al.
The difference between the instant application and the applied Liu art is that does not expressly teach a lyophilized preparation comprising atropine and a kit product obtained by means of a lyophilized preparation comprising atropine and the concentration of the chelating agent.
The deficiencies of the Liu et al are cured by the Yu and Quan Chunman.
Resolving the level of ordinary skill in the pertinent art.
Regarding the Claim 16, with respect to the lack of disclosing the kit obtained by means of using a lyophilized preparation comprising atropine, the Yu is silent about it. However, Liu et al does teach at least that the kit product comprising atropine and a product instruction manual (see page 14, a paragraph#0063), whereas Yu does teach the preparation of inclusion complex powder containing atropine using freeze drying method(a lyophilized preparation).
So, if the skilled artisan in the art had desired to develop a kit product by means of a lyophilized preparation comprising atropine, it would have been obvious to be motivated to combine a teaching of Liu’s et al Kit product with Yu’s lyophilized preparation-method together. This is because the skilled artisan in the art would expect such a combined formula to be successful and feasible as guidance shown in the prior art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Yu expressly discloses the atropine y cyclodextrin eye drop composition for treating myopia contains 1.0% atropine, ,18% y cyclodextrin, 0.05 mol/L of phosphate buffer (1.79%), and 1.0% polyvinyl alcohol and its preparation of inclusion complex powder using freeze drying method(a lyophilized preparation).
Similarly, Quan Chunman does teach the pharmaceutical composition for treating myopia development, eye drops, and the preparation method and the eye drops are composed of the following components, by w/v, 0.001%-2% of atropine sulfate, an osmotic pressure buffer agent such as sodium chloride , mannitol , 0%-2.2% of a stabilizer, 0%-0.05% of a bacteriostatic agent, such as benzalkonium chloride, benzalkonium bromide or ethylparaben (see pages 12-13 , a paragraph#0044 & 0047) and the balance of water, the pH value of the pharmaceutical composition is 3.0-8.5,
Furthermore, the prior art Liu et al does describe the atropine pharmaceutical composition by an ophthalmic preparation such as eye drops (see page 7, a paragraph#0019) containing atropine sulfate for treating myopia (see page 12, paragraphs#0054-0055) and its kit product which is a medicine box product comprising a drug and a product instruction manual (see page 14, a paragraph#0063).
All the three prior art are closely related to one and another by sharing atropine or atropine sulfate for the major ingredient for treating myopia.
Quan Chunman does offer a guidance for the concentration of other ingredients such as the buffer salt system, the matrix agent, the chelating agent , and the bacteriostatic agent for preparing an eye drop composition containing atropine ,whereas Liu et al does describe the kit comprising a atropine drug and a product instruction manual (see page 14, a paragraph#0063).
So, if the skilled artisan in the art had desired to develop a kit product by means of a lyophilized preparation comprising atropine along with the buffer salt system, the matrix agent, the chelating agent , and the bacteriostatic agent, it would have been obvious to be motivated to incorporate a teaching of Liu’s et al Kit product in combination with Quan Chunman’s specific concentrations of other ingredients into Yu’s lyophilized preparation-method in order to make a useful treatment-kit for the patient with myopia. This is because the skilled artisan in the art would expect such a combined procedure to be successful and feasible as guidance shown in the prior art.
Conclusion
Claims 1-20 are rejected.
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/TAYLOR V OH/Primary Examiner, Art Unit 1625 2/7/2026