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 .
Claims 17-32 are pending.
Claims 1-16 are cancelled.
Claims 18, 23-25, and 31 are amended.
Claims 17, 19-22, 26, 28-30 and 32 are withdrawn.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 18, 23-25, 27 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over WILSON (An overview of current techniques for ocular toxicity testing. Toxicology. 2015.) in view of AL-GHANANEEM (Phase I and Phase II Ocular Metabolic Activities and the Role of Metabolism in Ophthalmic Prodrug and Codrug Design and Delivery. Molecules. 2007) and OECD/OCDE (Reconstructed human Cornea-like Epithelium (RhCE) test method for identifying chemicals not requiring classification and labelling for eye irritation or serious eye damage. 2018).
Regarding claim 18,
WILSON teaches a method of direct application on eye cells, and predicting ocular irritancy or toxicity therefrom. The method comprises:
directly applying a test substance to rabbit corneal cell lines and incubated for 5 minutes (page 39, paragraph 2), which reads on applying the test substance to cells for a predefined time,
The cell viability is quantified and can be classified as irritancy GHS Category 1 (page 39, paragraph 2), which means there is a high level of toxicity and the sample tests positive for toxicity, which reads on quantifying or determining viability and/or cell killing of differentiated eye cells
The cell viability is quantified and can be classified as irritancy GHS Category 1 (page 39, paragraph 2), which means there is a high level of toxicity and the sample tests positive for toxicity, which reads on predicting ocular irritancy or toxicity therefrom by comparing the viability and/or cell killing od differentiated eye cells, respectively to the same for a predefined control or one or more test chemicals which have benchmark in vivo ocular irritation or ocular toxicity classifications, so as to thereby make the ocular irritancy or toxicity prediction
Note, the wherein limitations of the claim, are considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 2111.04: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 1690 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 2005).). This is in regards to the step of “wherein direct application indicates negative for ocular irritancy or toxicity where there is no significant change in the amount of viability and/or cell killing of said differentiated eye cells as compared to the predefined control, and wherein direct application indicates negative for ocular irritancy or toxicity where there is no significant change in the amount of viability and/or cell killing of said differentiated eye cells as compared to the predefined control”.
WISLON teaches another method of testing that comprises:
indirect application on differentiated eye cells
first applying saline (fig 2 ii), which reads on applying an aqueous solution to differentiated eye cells so as to form an aqueous layer thereon
then applying the test substance (fig 2 iii), which reads on applying thereon the same test substance as applied in 1) to form an overlay on top of the aqueous layer, thereby physically separating or minimizing contact of the test substance from the differentiated eye cells
the eye is then incubated for 10 seconds (page 35, paragraph 5), which reads on incubating so as to permit the aqueous layer to collect secretions from the differentiated eye cells, wherein the incubation time of the indirect application is greater than the predefined time in the direct application, thereby allowing time for differentiated eye cells secretions into the aqueous layer that can interact with the test substance and liquid phase metabolism, and possibly damage the differentiated eye cells
Toxic effects are then determined (page 35, paragraph 5), which reads on quantifying or determining viability and/or cell killing of the differentiated eye cells,
This test used for comparison to known values to determine the toxicity classification (page 35, paragraph 6), which reads on comparing the amount of viability and/or cell killing of the differentiated eye cells to an amount of viability and/or cell killing, respectively, of one or more testing chemicals which have benchmark in vivo ocular irritation or ocular toxicity classifications, so as to thereby make an ocular irritancy or toxicity prediction, wherein these one or more testing chemicals have been tested in vitro by the indirect application and
This test used for comparison to known values to determine the toxicity classification (page 35, paragraph 6), which reads on predicting ocular irritancy or toxicity therefrom by comparing the viability and/or cell killing, respectively, to the same for a predefined control or for one or more testing chemicals which have clinically graded benchmark in vivo ocular irritation or ocular toxicity classifications,
Multiple test can be used to determine the classification of substances (page 42, paragraph 5), which reads on simultaneous performance separately of 1 and 2
Note, the wherein limitations of the claim, are considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 2111.04: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 1690 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 2005).). This is in regards to the step of “wherein indirect application indicates negative for ocular irritancy or toxicity where there is no significant change in the amount of viability and/or cell killing as compared to the predefined control, and
wherein indirect application indicates positive for ocular irritancy or toxicity where there is a comparable or greater amount of viability and/or cell killing as compared to the predefined control or to a clinically graded benchmark classification for ocular irritancy or toxicity”.
WILSON does not teach adding an enzyme to the aqueous solution for the indirect method or using differentiated eye cells, such as reconstituted human corneal epithelium (RhCE) cells.
AL-GHANANEEM teaches that eye has metabolic processes that can protect and/or react with foreign substances such as drugs administered to the eye (page 374, paragraph 1) A drug applied to the surface of the eye may cross ocular–blood barriers where it may encounter metabolizing enzymes and cellular transporters before it distributes to the site of action (page 374, paragraph 2).
OECD/OCDE teaches that RhCE cells closely mimic the histological, morphological, biochemical and physiological properties of the human corneal epithelium and are commonly used in eye irritation testing (page 1, paragraph 3).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate adding an enzyme/enzyme inhibitor to the aqueous solution for indirect application. The person of ordinary skill in the art would have been motivated to make those modifications, because it would mimic a natural human eye more closely, since the natural human eye has many enzymes within it that can react in unknown ways when a drug is applied to it, and reasonably would have expected success because the references are in the same field of endeavor, such as adding test substances to eyes.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using RhCE cells. The person of ordinary skill in the art would have been motivated to make those modifications, because RhCE cells closely mimic the histological, morphological, biochemical and physiological properties of the human corneal epithelium and are commonly used in eye irritation testing, and reasonably would have expected success because the references are in the same field of endeavor, such as testing of substances for ocular purposes.
Regarding claim 23, AL-GHANANEEM teaches that enzyme inhibiters, such as 4-(2-aminoethyl)benzene sulfonyl fluoride, which is a sulfonyl fluoride, have been tested in the eyes in regards to drugs to determine metabolism of drugs administered to the eye (page 383, paragraph 2) and it would be obvious to combine as discussed above.
Regarding claim 24, AL-GHANANEEM teaches that Cytochrome P450 is an enzyme that is commonly found in the eye that reacts to applied drugs (page 376, paragraph 1) and it would be obvious to combine as discussed above.
Regarding claim 25, Note, the wherein limitations of the claim, are considered to simply express the intended result of a process step positively recited, which is not given patentable weight (See MPEP 2111.04: [T]he court noted (quoting Minton v. Nat'lAss'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQgd 1614, 1690 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.'" Hoffer v. Microsoft Corp., 405 F.3d 1396, 1399, 74 USPQgd 1481, 1483 (Fed. Cir. 2005).). This is in regards to the step of “wherein the enzymatic activity of the enzymatic reagent results from the activity of the differentiated eye cells and a negative control remains negative for toxicity or irritation, but the test substance acted upon by the enzymatic activity of the differentiated eye cells changes from nontoxic to toxic or from toxic to nontoxic as a result of this activity, and the time until toxicity is measured and used to predict if the test substance is an ocular irritant or toxin”.
Regarding claim 27, OECD/OCDE teaches that RhCE cells closely mimic the histological, morphological, biochemical and physiological properties of the human corneal epithelium and are commonly used in eye irritation testing (page 1, paragraph 3) and it would be obvious to combine as discussed above.
Regarding claim 31, WILSON teaches using saline (fig 2), which is commonly known as containing 9g/L of sodium chloride.
Response to Arguments
Applicant argues that WISLON does not teach using differentiated eye cells.
Examiner does not find the argument persuasive because as discussed above, OECD/OCDE teaches that RhCE cells closely mimic the histological, morphological, biochemical and physiological properties of the human corneal epithelium and are commonly used in eye irritation testing (page 1, paragraph 3) and it would be obvious to combine as discussed above.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/S.L.M./Examiner, Art Unit 1618 /JAKE M VU/Primary Examiner, Art Unit 1618
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