DETAILED ACTION
Status of Application
The response filed 06/29/2026 has been received, entered and carefully considered. The response affects the instant application accordingly:
Claims 1, 7-8, 10-11 have been amended.
Claims 1, 3, 7-11 are pending in the case.
Claims 1, 3, 7-11 are present for examination.
All grounds not addressed in the action are withdrawn or moot as a result of amendment.
New grounds of rejection are set forth in the current office action as a result of amendment.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
New Grounds of Rejection
Due to the amendment of the claims the new grounds of rejection are applied:
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.
Claims 1, 3, 7-11 are 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 recitation that the cysteamine as a sole active ingredient is indefinite as it unclear what is encompassed by the phrase as many excipients have activity including the claimed glycerol (instant claim 11) and instant claims 8-9 which recites additional actives and are subject the indefinite rejection below. Antioxidants are active ingredients, preservatives are active ingredients, osmotic agents are active ingredients, and lubricants; wherein are they excluded or included in the composition? The instantly claimed glycerol is recited as an excipient but has activity as it can lower intraocular pressure in glaucoma (see Goswamy) and has properties of promoting epithelial cell growth and blunting the damaging effects of high osmolarity on the ocular surface and is considered an active ingredient for dry eye (see Larson, Formularization of active Ingredients-Demulcents- Glycerin, Page 1 and 3-4); wherein it is unclear how the composition can only have cysteamine as the sole active ingredient as it is open to inclusion of glycerol which is an active ingredient. Is it directed to where the cysteamine is the sole therapeutic ingredient? This is also unclear as if cysteamine is a sole therapeutically active ingredient - the claimed glycerol is a therapeutic active ingredient as it can lower intraocular pressure in glaucoma and has properties of promoting epithelial cell growth and blunting the damaging effects of high osmolarity on the ocular surface wherein it is indefinite. It does not allow one to ascertain the metes and bounds of the claims as written. The indefinite issue for derivative is addressed above. For purposes of examination, the phrase is treated where the composition is open to other active components with cysteamine or a its pharmaceutically acceptable salt (i.e. glycerol, preservatives, lubricants), but not therapeutically conventional active drugs in the composition that comprises the method (i.e. omega 3 fatty acid, but the method is open to additional compositions and steps).
Response to Arguments:
Applicant’s arguments are centered on the assertions that the phrase “cysteamine or a pharmaceutically acceptable salt thereof as a sole active ingredient” means “individual active ingredient, administered alone” consistent with the data and disclosure of the specification, that there is no evidence why one of ordinary skill in the art would have a different understand different from the ordinary and customary meaning of the plain reading of the amended invention claimed which is consistent with the instant disclosure, that the inclusion of glycerol does not render the phrase indefinite as the specification can optionally include a pharmaceutically acceptable excipient, that even if one would be considered an active ingredient it is not understood by one of ordinary skill in the art to be effective in ameliorating dry eye symptoms or useful for dry eye with increased MMP activity.
This is fully considered but not persuasive.
Applicant’s argument that the phrase “cysteamine or a pharmaceutically acceptable salt thereof as a sole active ingredient” means “individual active ingredient, administered alone” is not persuasive as the sentence is “When referencing an individual active ingredient administered alone, a therapeutically effective dose refers to that ingredient alone” wherein the dose of 0.44% is to cysteamine alone, but does not resolve the indefiniteness of the claims which is that the claims recites for cysteamine is the sole active ingredient which is unclear as other components and excipient have activity such as antioxidant and preservatives as addressed above. This argument and Applicant’s argument that there is no evidence to have a different understanding from the ordinary and customary mean of the plain reading are not persuasive as a plain reading and understanding of the claim is the exclusion of any active that is not cysteamine at 0.44% wherein the issue of indefiniteness arises as other active components like antioxidants and preservatives have activity and are active components, Applicant’s arguments appear to be based on the assertion that the claims recite that cystamine is the sole therapeutically active ingredient which is not the breath claimed.
As for the assertion that the inclusion of glycerol does not render the phrase indefinite as the specification can optionally include a pharmaceutically acceptable excipient, and that even if one would be considered an active ingredient it is not understood by one of ordinary skill in the art to be effective in ameliorating dry eye symptoms or useful for dry eye with increased MMP activity; is fully considered but not persuasive. While Applicant recites glycerol in a dependent claim as an excipient, it still is an issue of indefiniteness as glycerol is known to have activity as it can lower intraocular pressure in glaucoma (see Goswamy) and has properties of promoting epithelial cell growth and blunting the damaging effects of high osmolarity on the ocular surface and is considered an active ingredient for dry eye (see Larson); wherein it is unclear as it appear to be in conflict with the recitation of cysteamine as the sole active. With regards to the assertion that one of skill in the art would not understand glycerol to be useful for dry eye, this is not persuasive nor accurate as evidenced by Larson which establishes that glycerol/glycerin is known active ingredient to be useful for dry eye. With regards to the assertion for dry eye with increased MMP, this is to the issue of prior art which is addressed below and MMP-9 is known to be elevated in the tears of patients with dry eyes as established by American Academy of Ophthalmology, wherein the dry eye is associated with increased MMP activity, and as addressed above Larson establishes that glycerol/glycerin is known active ingredient to be useful for dry eye which would include all forms of dry eye which is known to have increased MMP activity.
Accordingly, the rejection stands.
Claims 8-9 are 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 claims recite the method of claim 1 wherein the method comprises a further step of administering the composition with at least one additional active agent (instant claim 8) and wherein the at least one additional active agent is an MMP-9 inhibitor (instant claim 9), but depends from independent claim 1 which states that the composition for the method has cysteamine as a sole active ingredient at 0.44% wherein it is unclear how the same recited composition has an additional active agent when it depends form a claim where the sole active ingredient is cysteamine, wherein it broadens the claim from which it depends and indefinite. The composition cannot only have cysteamine as the only active and then have additional actives, it does not allow one to ascertain the metes and bounds of the claims as written. For purposes of examination, the claims are treated where the additional active(s) are in a separate composition and a separate step from the administration of the 0.44% cysteamine composition where cysteamine is the sole active ingredient as interpreted in the 112 rejection above.
Response to Arguments:
Applicant’s arguments are centered on the assertions that the amendments to the claim resolve the issue of indefiniteness and are supported by the specification citing [28,70]. This is fully considered but not persuasive. Paragraphs [28, 70] support for a composition with cysteamine and another active with an excipient; that can be administer as a single composition or in separate compositions. However this is not the breath claimed. It is not supportive for the instant claims which is for an additional active agent in the composition of clam 1 where the sole active ingredient in the composition is 0.44% cysteamine, wherein it broadens the claim from which it depends and indefinite.
Accordingly, the rejection stands.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 8-9 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The claims recites a further step of administering the composition of claim 1 with at least one additional active agent (instant claim 8) which is an MMP-9 inhibitor (instant claim 9), but depends from independent claim 1 which states that the composition for the method has 0.44% cysteamine as a sole active ingredient wherein claims 8-9 have the same recited composition with an additional active agent despite the recitation for cysteamine to be the only active wherein it broadens the claim from which it depends from.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1, 3, 7-8, 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Matier et al. (WO 2005/051328) in view of American Academy of Ophthalmology (Evaluating MMP-9 levels may help diagnose dry eye) and www.nidirect.gov.uk (Dry eye syndrome).
Rejection:
Matier et al. teaches treating eye conditions in patients including dry eye (keratoconjunctivitis sicca – including non-Sjogren’s presentations (does not recite Sjogren’s), the instant specification states that dysfunctional tear syndrome is the condition of having dry eyes [3]) with a composition comprising a hydroxylamine compound, a carrier/diluent, and further with a reducing agent that is preferably a sulfydryl compound such as β-mercaptoethylamine (also known as cysteamine) from about 0.1-about 5.0%w/v (claims 1, 13, 15-20; abstract, Page 4 paragraph 3-4, Page 7 paragraph 1 and 4, Page 8 last paragraph-Page 9 first line, Page 11 first paragraph). Administration can be by eye drop, wash or ointment (Page 8 paragraph 1, Page 10 paragraph 2, Page 13 first paragraph, claim 24). The reducing agent can be administered separately from the hydroxylamine or formulated together (claims 15-20, cysteamine/β-mercaptoethylamine in a separate composition from hydroxylamine-each therapeutic active in separate compositions (sole therapeutic active in their composition)). The composition can include tonicity agents and isotonic solutions such as 0.9% saline, viscosity agents like hydroxypropylcellulose and polyvinyl pyrrolidine, cosolvents like glycerin (glycerol, Page 11 paragraph 3-Page 12 first paragraph). The dose may be adjusted by the physician as needed and the dosing can be 1-4 times/day as long as needed and the dosing schedule may vary depending on the drug concentration and an ophthalmologist or one skilled in the art have the means to monitor the effectiveness of the dosage and dosage scheme and adjust accordingly (Page 10 last paragraph-Page 11 first paragraph, Page 17 last paragraph-Page 18 paragraph 2). Matier et al. teaches that the composition can have additional compounds known in the art for treating the disease (Page 17 paragraph 4, see full document specifically areas cited).
While Matier et al. does not expressly teach the exact claimed value of 0.44% for β-mercaptoethylamine (cysteamine), it is embraced by the taught range of Matier et al. (about 0.1-about 5.0%w/v ) wherein it would be prima facie obvious to optimize within the taught range to attain the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed value. It is implicit that the patient is diagnosed with the condition in order to be treated. It is also implicit if not prima facie obvious that the patient is human as the diseases are human diseases (i.e. glaucoma, dry eye, ERM is recited to be in people over 75). While Matier et al. does not expressly teach the exact claimed dosing regimen to each eye, Matier does teach that dosing can be 1-4 times/day as long as needed and the dose and dosing schedule may be adjusted by the physician as needed for effectiveness, and it is well known in the art that dry eye symptoms usually affect both eyes as established by www.nidirect.gov.uk (Symptoms of dry eye syndrome 2nd paragraph); wherein to would be prima facie obvious to one of ordinary skill in the art to adjust/optimize the dosing schedule such as 4 times a day which is within the taught schedule - and to use the composition for the entire duration of the condition (i.e. dry eye for months, years) to the affected eyes (i.e. both eyes) and attain the desired therapeutic/effective profile with a reasonable expectation of success absent evidence of criticality for a specific regimen schedule.
Matier does not expressly recite that the dry eye has elevated MMP activity, it does recite treating dry eye and MMP-9 is known to be elevated in the tears of patients with dry eyes as established by American Academy of Ophthalmology, wherein the dry eye is associated with increased MMP activity.
Response to Arguments:
Applicant’s arguments are centered on the assertions for unexpected results in Example 1 and that the amended claim 1 is commensurate in scope with the example asserting objective evidence of nonobviousness that it is to a new use for cysteamine, that cysteamine causes eye irritation where one would not had reasonably expected cysteamine to treat dry eye and that one would not have expected cysteamine to be useful for dry eye (dysfunctional tear syndrome), and that the Examiner failed to establish a prima facie case of obvious as the prior art do not teach/suggest the claim limitations.
This is fully considered but not persuasive.
Applicant’s argument that Example 1 presents with unexpected results and amended claim 1 which is to treating DTS associated with increased MMP activity with administering 0.44% cysteamine or its pharmaceutical salt as a sole active ingredient four times daily to each eye for at least four weeks to ameliorate dry eye in a human is fully considered but not persuasive. The indefinite issues are addressed above. The claims are not commensurate in scope with Example 1 which is only to a single concentration of 0.44% of cysteamine with one eyedrop given to each eye four times/day as the only compound in the method of treatment of dry eye for 30-37 days which is not commensurate in scope with the instant claims which is to any means of administration to the eye (not only to an eyedrop) with a broader range of time, and allows for the inclusion of other components and other steps (“comprising”). Additionally, the sole example of the specification demonstrates that the 0.44% cysteamine eye drop four times a day to each eye for 30-37 day was useful for the treatment – which supports for the prior art rejection above - it does not demonstrate any unexpected results nor comparative to show evidence of criticality for the claimed value and regimen which falls within the taught range of the prior art wherein it is prima facie obvious to optimize within the taught values with a reasonable expectation of success absent evidence of criticality for the claimed values which has not been presented with Matier which is the closest prior art. The claims are also broader than the example as the claims are open the inclusion of other components, other compositions, and other steps (as well as the indefiniteness issues addressed above).
With regards to the arguments that cysteamine causes eye irritation where one would not had reasonably expected cysteamine to treat dry eye is confusing as it is an argument for nonenablement of the instant claimed invention. This is neither persuasive nor accurate as the safety data sheet is directed to a 100% pure product as an eye irritant, not a diluted formulation at the concentrations in the prior art about 0.1-about 5.0%w/v like 0.44% which is ophthlamically useful and reads on the instant claims.
Applicant’s assertion that the state of the art does not teach the claimed method which is to a new use for treating dry eye with cysteamine and the prior art does not teach the instant claims is neither accurate nor persuasive as the prior art meets the claimed limitations and contrary to Applicant’s assertion that there is not a prima facie case of obviousness - the basis for obviousness is articulated in the rejection above. The prior art of Matier et al. teaches treating dry eye a hydroxylamine compound, a carrier/diluent, and a reducing agent that is preferably a sulfydryl compound such as β-mercaptoethylamine (also known as cysteamine) which can be in separate compositions (sole therapeutic active in their composition) and MMP-9 is known to be elevated in the tears of patients with dry eyes as established by American Academy of Ophthalmology, wherein the dry eye is associated with increased MMP activity. Wherein optimization of the cysteamine concentration within the taught range and optimization of the dosing schedule within the taught regimen to treat the patient for the duration of the condition (i.e. 1-4x/day as long as needed, Page 17 last paragraph) is prima facie obvious with a reasonable expectation of success absent evidence of criticality for the specific dose and/or specific regimen schedule which has not been presented (MPEP 2144.05 IIIA). Contrary to Applicant’s arguments to the inclusion of hydroxylamine in a separate composition, this is not persuasive as the claims allow for the inclusion of other compositions to be administered (“comprising administering”) and the dependent claims recite the administration of another active agent which allows for hydroxylamine.
Accordingly, the rejection stands.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Matier et al. (WO 2005/051328) in view of American Academy of Ophthalmology (Evaluating MMP-9 levels may help diagnose dry eye) and www.nidirect.gov.uk (Dry eye syndrome) as applied to claims 1, 3, 7-8, 10-11 above, further in view of Hong et al. (U.S. Pat. Pub. 2009/0131303).
Rejection:
The teachings of Matier et al. in view of American Academy of Ophthalmology and www.nidirect.gov.uk are addressed above.
Matier et al. in view of American Academy of Ophthalmology and www.nidirect.gov.uk does not teach the inclusion of an MMP-9 inhibitor but does teach that the composition can have additional compounds known in the art for treating the disease.
Hong et al. teaches protease-inhibiting peptide substrates that are MMP-9 inhibitors which are useful for treating dry eye (abstract, [2, 5], claims 7 and 9-10).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate an MMP-9 inhibitor like the disclosed protease-inhibiting peptide substrates as suggested by Hong et al. and produce the claimed invention, as it is prima facie obvious to combine actives useful for the same condition as their additive effect with a reasonable expectation of success and the prior art of Matier et al. teaches combination of actives with hydroxylamine administered separately or together for the treatment.
Response to Arguments:
Applicant’s arguments are those presented with regards to Matier and AAO which are addressed above. Applicant also asserts that Hong does not teach the claimed method. Applicant’s remaining arguments that Hong does not teach the claimed method is not persuasive as this is an argument against the reference 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).
Accordingly, the rejection stands.
Claims 1, 3 are rejected under 35 U.S.C. 103 as being unpatentable over Matossian (Improve the Diagnosis, Management and Treatment of Inflammatory Dry Eye) in view of Rubin (U.S. Pat. Pub. 2008/0242735) and www.nidirect.gov.uk (Dry eye syndrome).
Matossian teaches that dry eye (keratoconjunctivitis, including non-Sjogren’s presentations (does not recite Sjogren’s) is known to a multifactorial disease of the tears and ocular surface and presents with elevated MMP-9 (Page 1) and patient report that their eyes feel sandy or scratchy with increasing symptoms over time (plural, both eyes are impacted (Page 2 1st paragraph, see full document specifically areas cited).
Matossian does not expressly teach treatment with cysteamine but does teach that dry eye presents with elevated MMP-9 and can present in both eyes which is well known in the art and also established by www.nidirect.gov.uk (Symptoms of dry eye syndrome 2nd paragraph).
Rubin teaches treatment of MMP pathologies with elevated MMP such as MMP-9 with the administration of cysteamine including eye drops forms for pathologies affecting the eyes (abstract, claim 1, 9-11, 13-14, [11, 15-18]). The amount of cysteamine is about 0.1-about 0.5% like about 0.5% (embraces 0.44%) and given between about 2-12 times/day (claim 9-11 and 13-14, [11]). Rubin teaches that the amount of cysteamine for effective therapy depend on many factors and dosages can be titrated to optimize safety and efficacy as aminal testing is used for predictive indication of a human therapeutic dosage (for a human patient, [21-22], see full document specifically areas cited).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat dry eye with cysteamine as suggested by Rubin and produce the claimed invention, as it is prima facie obvious to use a composition useful for elevated MMP eye conditions for an eye condition with elevated MMP-9 with a reasonable expectation of success. It is implicit that the patient is diagnosed with the condition in order to be treated. While the prior art does not expressly teach the exact claimed amount of cysteamine and dosing regime, it is embraced by the prior art as Rubin does teach that amount of cysteamine is from about 0.1-about 0.5% and dosing can be given between about 2-12 times/day and that it can be titrated to optimize safety and efficacy; wherein to would be prima facie obvious to one of ordinary skill in the art to adjust/optimize the amount of cysteamine and dosing schedule to each eye within the taught range and to use the composition for the duration of the condition to attain the desired therapeutic/effective profile with a reasonable expectation of success absent evidence of criticality for a specific range or regimen schedule.
Response to Arguments:
Applicant’s arguments centered on the assertions that Matossian is silent on cysteamine, that Rubin is silent on the treatment of dry eye, that Rubin is treating pterygium which is different than dry eye, the assertions for unexpected results in Example 1 and that the amended claim 1 is commensurate in scope with the example asserting objective evidence of nonobviousness that it is to a new use for cysteamine, that cysteamine causes eye irritation where one would not had reasonably expected cysteamine to treat dry eye and that one would not have expected cysteamine to be useful for dry eye (dysfunctional tear syndrome), and that the Examiner failed to establish a prima facie case of obvious as the prior art do not teach/suggest the claim limitations.
This is fully considered but not persuasive.
With regards to the assertion that Matossian is silent on cysteamine and that Rubin is silent on the treatment of dry eye, this is not persuasive as it is against the references individually and 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’s argument appears to want that the instant method be in a single teaching or anticipatory which is not the basis for a prima facie case of obviousness.
The assertion that Rubin is to treating a pterygium which is different that dry eye (DTS), is against the reference individually and 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). Additionally, Rubin is not only to pterygium as asserted by Applicant - but to treating a pathology in which increased production of MMP is implicated with an eye drop composition comprising cysteamine from about 0.1%-about 0.5% - and Matossian establishes that dry eye is a that presents with increased MMP-9 wherein it is a pathology with increased production of MMP is implicated and it would be obvious to utilize the treatment taught by Rubin for the condition in which increased production of MMP is implicated with a reasonable expectation of success.
Applicant’s argument that Example 1 presents with unexpected results and amended claim 1 which is to treating DTS associated with increased MMP activity with administering 0.44% cysteamine or its pharmaceutical salt as a sole active ingredient four times daily to each eye for at least four weeks to ameliorate dry eye in a human is fully considered but not persuasive. The indefinite issues are addressed above. The claims are not commensurate in scope with Example 1 which is only to a single concentration of 0.44% of cysteamine with one eyedrop given to each eye four times/day as the only compound in the method of treatment of dry eye for 30-37 days which is not commensurate in scope with the instant claims which is to any means of administration to the eye (not only to an eyedrop) with a broader range of time, and allows for the inclusion of other components and other steps (“comprising”). Additionally, the sole example of the specification demonstrates that the 0.44% cysteamine eye drop four times a day to each eye for 30-37 day was useful for the treatment – which supports for the prior art rejection above - it does not demonstrate any unexpected results nor comparative to show evidence of criticality for the claimed value and regimen which falls within the taught range of the prior art wherein it is prima facie obvious to optimize within the taught values with a reasonable expectation of success absent evidence of criticality for the claimed concentration and/or specific regimen which has not been presented. The claims are also broader than the example as the claims are open the inclusion of other components, other compositions, and other steps (as well as the indefiniteness issues addressed above).
With regards to the arguments that cysteamine causes eye irritation where one would not had reasonable expected cysteamine to treat dry eye is confusing as it is an argument for nonenablement of the instant claimed invention. This is neither persuasive nor accurate as the safety data sheet is directed to a 100% pure product as an eye irritant, not a diluted formulation at the concentrations in the prior art at about 0.1-about 0.5% like 0.44% which is ophthlamically useful and reads on the instant claims.
Applicant’s assertion that the state of the art does not teach the claimed method which is to a new use for treating dry eye with cysteamine and the prior art does not teach the instant claims is neither accurate nor persuasive as the prior art meets the claimed limitations and the basis for obviousness is articulated in the prima facie case of obvious rejection above; which establishes that dry eye presents with elevated MMP-9 and Rubin teaches a method of treating MMP pathologies with elevated MMP such as MMP-9 with the administration of cysteamine including eye drops forms with cysteamine from about 0.1-about 0.5% (embracing 0.44%) and given between about 2-12 times/day (embracing 4x/day) it is prima facie obvious to use a composition useful for elevated MMP eye conditions for an eye condition with elevated MMP-9 with a reasonable expectation of success absent evidence of criticality for the claimed concentration/regimen which has not been presented.
Accordingly, the rejection stands.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Matossian (Improve the Diagnosis, Management and Treatment of Inflammatory Dry Eye) in view of Rubin (U.S. Pat. Pub. 2008/0242735) and www.nidirect.gov.uk (Dry eye syndrome) as applied to claims 1, 3 above, in view of Hong et al. (U.S. Pat. Pub. 2009/0131303).
Rejection:
The teachings of Matossian in view of Rubin and www.nidirect.gov.uk are addressed above.
Matossian in view of Rubin and www.nidirect.gov.uk does not teach the inclusion of an MMP-9 inhibitor but does teach treating eye diseases like dry eye with elevated MMP with cysteamine.
Hong et al. teaches protease-inhibiting peptide substrates that are MMP-9 inhibitors which are useful for treating dry eye (abstract, [2, 5], claims 7 and 9-10).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate an MMP-9 inhibitor like the disclosed protease-inhibiting peptide substrates as suggested by Hong et al. and produce the claimed invention, as it is prima facie obvious to combine actives useful for the same condition as their additive effect with a reasonable expectation of success.
Response to Arguments:
Applicant’s arguments are those presented for Matossian and Rubin which are addressed above. Applicant’s remaining arguments are to assertion that Hong does not teach the administration of cysteamine as instantly claimed which is not persuasive as it is against the reference individually and 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).
Accordingly, the rejection stands.
Claims 7 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Matossian (Improve the Diagnosis, Management and Treatment of Inflammatory Dry Eye) in view of Rubin (U.S. Pat. Pub. 2008/0242735) and www.nidirect.gov.uk (Dry eye syndrome) as applied to claims 1, 3 above, in view of Matier et al. (WO 2005/051328).
Rejection:
The teachings of Matossian in view of Rubin and www.nidirect.gov.uk are addressed above.
Matossian in view of Rubin and www.nidirect.gov.uk does not expressly teach the inclusion of certain excipients like glycerin (glycerol) but does teach the method of treating dry eye with a cysteamine eyedrop solution.
Matier et al. teaches compositions for treating eye conditions in patients like dry eye can contain excipients like tonicity agents such as sodium chloride for isotonic solutions such as 0.9% saline, viscosity agents (thickener helps alleviate symptoms), and cosolvents like glycerin (glycerol, Page 11 paragraph 3-Page 12 first paragraph).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate saline as suggested by Matier et al. and produce the claimed invention, as it is prima facie obvious to incorporate known conventional ophthalmic excipients in ophthalmic solutions for their known purpose with a reasonable expectation of success.
Response to Arguments:
Applicant’s arguments are those presented to Matossian and Rubin which are addressed above. Applicant’s remaining arguments are to assertion that Matier does not cure the deficiencies of Matossian and Rubin which is not persuasive as it is against the reference individually and 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).
Accordingly, the rejection stands.
Conclusion
Claims 1, 3, 7-11 are rejected.
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 GIGI GEORGIANA HUANG whose telephone number is (571)272-9073. The examiner can normally be reached Monday-Thursday 9:00-5:00pm.
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/GIGI G HUANG/Primary Examiner, Art Unit 1613
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