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 1-2, 4-6, 11 and 13-15 are pending.
Claims 3, 7-10, 12 are cancelled.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn.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.
Claims 1-2, 4-6, 11 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over BEUERMAN (US 8080428B2) in view of TEPELUS (Correlation between corneal innervation and inflammation evaluated with confocal microscopy and symptomatology in patients with dry eye syndromes: a preliminary study. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2017.).
Regarding claim 1, BEUERMAN teaches a method of diagnosing and treating dry mucosa, also called dry eye, in a subject (abstract), wherein BEUERMAN teaches that Sjogren Syndrome causes dry eye (column 1, paragraph 1). The method comprises providing a sample from a subject (claim 1), which reads on obtaining a sample from the subject. The expression of S100 A9 was measured (Claim 2), which reads on measuring an amount of a marker for a nerve abnormality in an eye present in the sample, wherein expression of the marker is correlated with at least one parameter selected from the group consisting of corneal nerve branch density (CNBD), corneal nerve fiber total branch density (CTBD), corneal nerve fiber length (CNFL). The expression levels were compared to reference values from control subjects that are not experiencing dry eye (Claim 1), which reads on comparing the measured amount of the marker with an amount of the marker in a sample obtained from a healthy individual to determine whether the subject has a nerve abnormality in the eye. Prolactin and/or androgen are administered to the subject to alleviate the symptoms of dry eye (Example 12), which reads on administering an effective amount of a drug for treating or reducing the risk of nerve abnormality to a subject determined to have a nerve abnormality.
Regarding claims 2, 4 and 5, BEAUERMAN measures S100 A9 (Claim 2). Applicant’s specification discloses protein S100-A9 has a correlation with the corneal nerve branch density, (CNBD and CTBD) and corneal nerve fiber length (CNFL) so that they are considered as markers which reflect the condition of nerve abnormality in the eye (Page 50, paragraph 2).
Regarding claim 6, BEUERMAN teaches a step of detecting the marker by reacting the marker with a chemical, such as an antibody (Column 3, paragraph 4).
Regarding claim 11, BEUERMAN teaches a method of diagnosing and treating dry mucosa, also called dry eye, in a subject (abstract). The method comprises providing a sample from a subject (claim 1), which reads on obtaining a sample from the subject. The expression of multiple biomarkers were measured in the method including Glucose-6-phosphate isomerase (table 1), which reads on measuring an amount of a marker for dry eye present in the sample, wherein expression of the marker is correlated with at least one parameter selected from the group consisting of tear film break-up time (BUT), Ocular Surface Disease Index (OSDI), and Dry Eye Questionnaire 5 (DEQ5). The expression levels were compared to reference values from control subjects that are not experiencing dry eye (Claim 1), which reads on comparing the measured amount of the marker with an amount of the marker in a sample obtained from a healthy individual to determine that the subject has dry eye based on the amount of the marker. Prolactin and/or androgen are administered to the subject to alleviate the symptoms of dry eye (Example 12), which reads on administering an effective amount of a drug for treating or reducing a risk of dry eye to a subject determined to have dry eye.
Note, Applicant’s specification further discloses that glucose-6-phosphate isomerase is in correlation with BUT, OSDI and DEQ5 (Page 28. Paragraph 2).
Regarding claim 14, BEUERMAN teaches a step of detecting the marker by reacting the marker with a chemical, such as an antibody (Column 3, paragraph 4).
Regarding claim 15, BEUERMAN teaches a method of diagnosing and treating dry mucosa, also called dry eye, in a subject (abstract). The method comprises providing a sample from a subject (claim 1), which reads on obtaining a sample from the subject. The expression of multiple biomarkers were measured in the method including S100 A9 (Claim 2), S100 A8 (Example 13), and Glucose-6-phosphate isomerase (table 1), which reads on measuring an amount of a first marker in the sample that changes expression in correlation with at least one parameter selected from the group consisting of CNBD, CTBD, CNFD, CNFL, and corneal nerve tortuosity and an amount of a second marker in the sample that changes expression in correlation with at least one parameter selected from the group consisting of tear film break-up time (BUT, Ocular Surface Disease Index (OSDIJ, and Dry Eye Questionnaire 5 (DEQ5). The expression levels were compared to reference values from control subjects that are not experiencing dry eye (Claim 1), which reads on comparing the measured amounts of each of the first and second markers with respective amounts of the first and second markers in a sample obtained from a healthy individual to determine that the subject has dry eye associated with a nerve abnormality based on the amounts of each of the first and second markers. Prolactin and/or androgen are administered to the subject to alleviate the symptoms of dry eye (Example 12), which reads on administering an effective amount of a drug for treating or reducing a risk of dry eye associated with a nerve abnormality to a subject determined to have dry eye associated with a nerve abnormality.
Note, Applicant’s specification discloses protein S100-A9 has a correlation with the corneal nerve branch density, (CNBD and CTBD) and corneal nerve fiber length (CNFL). Applicant’s specification further discloses that glucose-6-phosphate isomerase is in correlation with BUT, OSDI and DEQ5 (Page 28. Paragraph 2).
BEUERMAN teaches that the method used for the detection, identification, and/or quantification at least one biomarker or a group of biomarkers in tear fluid of a subject provides the basis for diagnosing the condition of dry eyes due to any cause (Column 7). BEUERMAN further teaches that Sjogren Syndrome causes dry eye and is a point of interest for the method being performed (column 1, paragraph 1).
BEUERMAN does not explicitly teach treating an eye nerve abnormality in a subject in need thereof.
TEPELUS teaches that Sjogren Syndrome causes dry eye and alters the corneal nerves of the eye, such as affecting corneal nerve fiber density (CNFD) (abstract, conclusions), which reads on an eye nerve abnormality.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate treating an eye nerve abnormality in a subject in need thereof. The person of ordinary skill in the art would have been motivated to make those modifications, because Sjogren Syndrome causes eye nerve abnormalities, and reasonably would have expected success because BEUERMAN teaches a method of diagnosing and treating dry eye caused by Sjogren Syndrome.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over BEUERMAN (US 8080428B2) and TEPELUS (Correlation between corneal innervation and inflammation evaluated with confocal microscopy and symptomatology in patients with dry eye syndromes: a preliminary study. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2017.) as applied to claims 1-2, 4-6, 11 and 14-15 above, and further in view of SORIA (Tear proteome analysis in ocular surface diseases using label-free LC-MS/MS and multiplexed-microarray biomarker validation. Scientific Reports. 2017.).
BEUERMAN and TEPELUS teach Applicant’s invention as discussed above.
BEUERMAN and TEPELUS do not teach measuring the expression of antileukoproteinase.
SORIA teaches that the expression of antileukoproteinase (SLPI) is used to analyze dry eye in subjects (abstract). The expression of S100-A8 is also used to analyze subjects for dry eye (Page 5, paragraph 7).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate measuring the expression of antileukoproteinase. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because S100-A8 and antileukoproteinase are functional equivalents of biomarkers commonly measured for dry eye.
Response to Arguments
With regard to claims 1, 2, and 4-6, Beuerman does not teach or suggest a method of treating an eye nerve abnormality in a subject in need thereof, as recited in these claims. As stated in the Office Action, Beuerman relates to methods of diagnosing and treating dry mucosa, such as dry eye, which is a different condition than a nerve abnormality in the eye. The Office Action cites Example 12 of Beuerman as reading on the recited step of administering an effective amount of a drug for treating or reducing a risk of nerve abnormality, but Beuerman does not teach or suggest treating a subject having a nerve abnormality in the eye, or that the prolactin used in Example 12 to treat "dry eye due to downregulation of prolactin-inducible protein (PIP)" would be effective for treating a nerve abnormality in the eye. Accordingly, the §102 rejection of claims 1, 2, and 4-6 is improper, and should be withdrawn.
The examiner does not find the argument persuasive because although BEUERMAN does not explicitly teach treating an eye nerve abnormality in a subject in need thereof.
TEPELUS teaches that Sjogren Syndrome causes dry eye and alters the corneal nerves of the eye, such as affecting corneal nerve fiber density (CNFD) (abstract, conclusions), which reads on an eye nerve abnormality.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate treating an eye nerve abnormality in a subject in need thereof. The person of ordinary skill in the art would have been motivated to make those modifications, because Sjogren Syndrome causes eye nerve abnormalities, and reasonably would have expected success because BEUERMAN teaches a method of diagnosing and treating dry eye caused by Sjogren Syndrome.
With regard to claims 11 and 13-14, these claims recite methods of treating dry eye in a subject in need thereof, but the recited methods are not taught or suggested by Beuerman. For example, Beuerman does not teach or suggest measuring an amount of a marker for dry eye that is correlated with at least one parameter selected from the group consisting of Tear film break-up time (BUT), Ocular Surface Disease Index (OSDI), and Dry Eye Questionnaire 5 (DEQ5), let alone measuring an amount of any the markers recited in claim 11 as amended herein. Accordingly, Applicant respectfully urges reconsideration and withdrawal of the §102 rejection of claims 11 and 13-14.
The examiner does not find the argument persuasive because regarding claim 11, BEUERMAN teaches a method of diagnosing and treating dry mucosa, also called dry eye, in a subject (abstract). The method comprises providing a sample from a subject (claim 1), which reads on obtaining a sample from the subject. The expression of multiple biomarkers were measured in the method including Glucose-6-phosphate isomerase (table 1), which reads on measuring an amount of a marker for dry eye present in the sample, wherein expression of the marker is correlated with at least one parameter selected from the group consisting of tear film break-up time (BUT), Ocular Surface Disease Index (OSDI), and Dry Eye Questionnaire 5 (DEQ5). The expression levels were compared to reference values from control subjects that are not experiencing dry eye (Claim 1), which reads on comparing the measured amount of the marker with an amount of the marker in a sample obtained from a healthy individual to determine that the subject has dry eye based on the amount of the marker. Prolactin and/or androgen are administered to the subject to alleviate the symptoms of dry eye (Example 12), which reads on administering an effective amount of a drug for treating or reducing a risk of dry eye to a subject determined to have dry eye.
Note, Applicant’s specification further discloses that glucose-6-phosphate isomerase is in correlation with BUT, OSDI and DEQ5 (Page 28. Paragraph 2).
With regard to claim 15, this claim recites methods of treating dry eye associated with a nerve abnormality in a subject in need thereof, wherein the method comprises measuring an amount of a first marker that changes expression in correlation with at least one parameter selected from the group consisting of CNBD, CTBD, CNFD, CNFL, and corneal nerve tortuosity, and an amount of a second marker that changes expression in correlation with at least one parameter selected from the group consisting of tear film break-up time (BUT), Ocular Surface Disease Index (OSDI), and Dry Eye Questionnaire 5 (DEQ5). Beuerman does not teach or suggest such methods. For example, Beuerman at least does not teach or suggest measuring an amount of a marker according to the "second marker" of claim 15 that changes expression in correlation with at least one parameter selected from the group consisting of tear film break-up time (BUT), Ocular Surface Disease Index (OSDI), and Dry Eye Questionnaire 5 (DEQ5), let alone measuring an amount of any of the "second markers" recited in claim 15 as amended herein. Accordingly, Applicant respectfully urges reconsideration and withdrawal of the§ 102 rejection of claim 15.
The examiner does not find the argument persuasive because regarding claim 15, BEUERMAN teaches a method of diagnosing and treating dry mucosa, also called dry eye, in a subject (abstract). The method comprises providing a sample from a subject (claim 1), which reads on obtaining a sample from the subject. The expression of multiple biomarkers were measured in the method including S100 A9 (Claim 2) and Glucose-6-phosphate isomerase (table 1), which reads on measuring an amount of a first marker in the sample that changes expression in correlation with at least one parameter selected from the group consisting of CNBD, CTBD, CNFD, CNFL, and corneal nerve tortuosity and an amount of a second marker in the sample that changes expression in correlation with at least one parameter selected from the group consisting of tear film break-up time (BUT, Ocular Surface Disease Index (OSDIJ, and Dry Eye Questionnaire 5 (DEQ5). The expression levels were compared to reference values from control subjects that are not experiencing dry eye (Claim 1), which reads on comparing the measured amounts of each of the first and second markers with respective amounts of the first and second markers in a sample obtained from a healthy individual to determine that the subject has dry eye associated with a nerve abnormality based on the amounts of each of the first and second markers. Prolactin and/or androgen are administered to the subject to alleviate the symptoms of dry eye (Example 12), which reads on administering an effective amount of a drug for treating or reducing a risk of dry eye associated with a nerve abnormality to a subject determined to have dry eye associated with a nerve abnormality.
Note, Applicant’s specification discloses protein S100-A9 has a correlation with the corneal nerve branch density, (CNBD and CTBD) and corneal nerve fiber length (CNFL). Applicant’s specification further discloses that glucose-6-phosphate isomerase is in correlation with BUT, OSDI and DEQ5 (Page 28. Paragraph 2).
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
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/S.L.M./ Examiner, Art Unit 1618 /JAKE M VU/Primary Examiner, Art Unit 1618
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