FINAL ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
This action is in response to papers filed 10/01/2025 in which claims 4, 9-10, 15-17, 23, and 27-48 were canceled; claims 1 and 8 were amended; and claims 49-55 were newly added. All the amendments have been thoroughly reviewed and entered.
Claims 1-3, 5-8, 11-14, 18-22, 24-26, and 49-55 are under examination.
Maintained-Modified Rejection
Modification Necessitated by Applicant’s Claim Amendment
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 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(s) 1-3, 5-8, 11-14, 18-22, 24-26, and 49-55 is/are rejected under 35 U.S.C. 103 as being unpatentable over Beckman et al (US 2019/0133933 A1; previously cited) in view of Gross (US 2015/0190554 A1).
Regarding claims 1, 49 and 52, Beckman teaches a method of reducing intraocular pressure (IOP) in the eye of a subject in need thereof, the method comprising injecting a non-pharmacologically active formulation comprising a gel injectate such as a hyaluronic acid based gel or hydrogel into a suprachoroidal space (SCS) of the eye (Abstract; [0006]-[0011], [0033]-[0046], [0055]-[0065]; claims 1-16, 26-44 and 53-56). Beckman teaches the formulation provide reduction of IOP for at least 4 weeks ([0009], [0044]; claim 7). Beckman teaches the reduction intraocular pressure is due to the increased in trabecular meshwork outflow as a result from the introduction of the gel injectate that formed a hydrogel in the suprachoroidal space (Abstract; [0007], [0010], [0033]-[0034], [0036], [0041], [0043]; claims 1-5, 11 and 29-38). It is noted that the hyaluronic acid based “hydrogel” as taught in Beckman is a “crosslinked” hydrogel, as hydrogel are formed by crosslinking of a liquid hydrogel precursor solution containing hyaluronic acid, as evidenced by Gross (Abstract; [0008], [0015], [0022] and [0195]).
While Beckman does not expressly teach the crosslinked hydrogel is a chemically crosslinked, it would have been to use a gel injectate that is chemically crosslinked to form the resultant hydrogel is introduced in the suprachoroidal space, in view of the guidance from Gross.
Gross teaches a hyaluronic-acid based hydrogel formed from a liquid hydrogel precursor containing thiol-modified hyaluronan, and crosslinking agent containing a thiol-reactive crosslinking agent such as polyethylene glycol diacrylate (PEGDA) ([0005]-[0022], [0026]-[0036], [0038]-[0048], [0099]-[0155], [0166], [0173]-[0195], [0200], [0207]-[0219], [0231]-[0232]). Gross teaches the hydrogel is used for reducing intraocular pressure to treat glaucoma through increasing aqueous outflow through the normal trabeculocanalicular pathway ([0005], [0166], [0200], and [0232]). Gross teaches hydrogel produced from liquid hydrogel precursor solutions containing PEG comprising ester chains (e.g., PEGDA) can be optimize to control the rate of degradation of the resulting hydrogel (e.g., optimizing the concentration of ester chains) such as the resulting hydrogel degrades in several months or between one and two years ([0013]-[0017], [0173]-[0195] and [0231]-[0232]). Gross teaches the crosslinking agent can be added to the liquid hydrogel precursor before, during or after the introduction of the liquid precursor solution into the location within the eye that can result in reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork (Abstract; [0005]-[0010], [0016]-[0038], [0166], [0200], and [0232]).
It would have been obvious to one of ordinary skill in the art to use a chemically crosslinked hydrogel as the hydrogel material that is introduced in the suprachoroidal space (SCS) of the eye of Beckman by using the liquid hydrogel precursor containing thiol-modified hyaluronan as taught in Gross and crosslinking said liquid hydrogel precursor (a gel injectate) by adding a crosslinking agent such as polyethylene glycol diacrylate (PEGDA) before, during or after the introduction of the liquid precursor solution into the location within the eye that can result in reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Beckman and Gross are commonly drawn to using crosslinked hyaluronic acid hydrogel for treating glaucoma by reducing intraocular pressure in the eye via increasing aqueous outflow of the trabecular meshwork, and Gross provided the guidance for using a chemically crosslinked hydrogel as the hydrogel material formed by crosslinking the liquid hydrogel precursor (a gel injectate) via adding a crosslinking agent such as polyethylene glycol diacrylate (PEGDA) before, during or after the introduction of the liquid precursor solution into the location within the eye so that the resultant chemically crosslinked hydrogel that is formed reduces intraocular pressure in the eye by increasing aqueous outflow of the trabecular meshwork, and such chemically crosslinked hyaluronic acid-based hydrogel is useful for reducing intraocular pressure to treat glaucoma for an extended period of time due to the hydrogel does not degrade unto several months (Gross: Abstract; [0005]-[0010], [0013]-[0038], [0166], [0173]-[0195], [0200], and [0232]). It is noted that the objective of Beckman is also to reducing intraocular pressure to treat glaucoma for an extended period of time (Beckman: Abstract; [0007], [0010], [0033]-[0034], [0036], [0041], [0043]-[0044]; claims 1-5, 11 and 29-38). Thus, an ordinary artisan seeking to sustain the reduction of intraocular pressure for an extended period of time, would have looked to using a chemically crosslinked hydrogel as the hydrogel material that is introduced in the suprachoroidal space (SCS) of the eye of Beckman by using the liquid hydrogel precursor containing thiol-modified hyaluronan as taught in Gross and crosslinking said liquid hydrogel precursor (a gel injectate) by adding a crosslinking agent such as polyethylene glycol diacrylate (PEGDA) before, during or after the introduction of the liquid precursor solution into the location within the eye that can result in reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork, and achieve Applicant’s claimed invention with reasonable expectation of success.
Regarding claim 2, Beckman teaches the composition is injected through a microneedle inserted into the eye at a location 5 to 6 mm from the limbus, in the superior temporal quadrant (a location posterior to the limbus) ([0074]).
Regarding claim 3, Beckman teaches the subject is human and is in need of treatment for glaucoma ([0005], [0015]-[0016], [0055], and [0232]).
Regarding claims 5-8, Beckman the formulation provide reduction of IOP sustained for at least 2 months, at least 3 months, at least 4 months or at least 6 months ([0009], [0044]; claim 7). It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985). Absent some demonstration of unexpected results showing criticality from the claimed parameters, the optimization of the reduction in IOP would have been obvious before the effective filing date of Applicant’s invention. See MPEP §2144.05 (I)-(II).
Regarding claim 11, as discussed above, Beckman teaches injecting a non-pharmacologically active formulation comprising a hyaluronic acid based hydrogel formed from a gel injectate, into a suprachoroidal space (SCS) of the eye. Gross teaches and provide the guidance for forming the hydrogel in situ by injecting the liquid hydrogel precursor solution (a gel injectate) at a site of interest in the eye and crosslinking of the liquid hydrogel precursor solution to form the chemically crosslinked hydrogel that is used for reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork (Gross: [0005]-[0022], [0026]-[0036], [0038]-[0048], [0099]-[0155], [0166], [0173]-[0195], [0200], [0207]-[0219], [0231]-[0232]). Thus, it would have been obvious to form the hydrogel of Beckman in view of Gross in the SCS in situ by using the liquid hydrogel precursor containing thiol-modified hyaluronan as taught in Gross and crosslinking said liquid hydrogel precursor (a gel injectate) by adding a crosslinking agent such as polyethylene glycol diacrylate (PEGDA) before, during or after the introduction of the liquid precursor solution into the location within the eye (i.e., SCS of Beckman) that can result in reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork.
Regarding claim 12, Gross teaches the liquid hydrogel precursor solution that is used for forming the chemically crosslinked hydrogel is formulated such that the resultant hydrogel degrades in several months ([0013]-[0017], [0173]-[0195] and [0231]-[0232]).
Regarding claims 13-14, Beckman teaches the non-pharmacologically active formulation comprising a hyaluronic acid based hydrogel formed from a gel injectate is expanded in the SCS (Beckman: claim 18). Beckman teaches the formulation provide reduction of IOP sustained for at least 2 months, at least 3 months, at least 4 months or at least 6 months (Beckman: [0009], [0044]; claim 7). Gross teaches hyaluronic-acid based hydrogel formed from a liquid hydrogel precursor containing thiol-modified hyaluronan, and crosslinking agent containing a thiol-reactive crosslinking agent such as polyethylene glycol diacrylate (PEGDA), wherein the hydrogel degrades in several months (Gross: [0013]-[0017], [0173]-[0195] and [0231]-[0232]). Thus, it would have been reasonably obvious that the chemically crosslinked hydrogel of Beckman in view of Gross would sustain the expansion of SCS over a period of at least 60 days, at least 90 days, at least 120 days, at least 180 days, or between 90 and 180 days as recited in claims 13 and 14, respectively because Beckman indicated that the hyaluronic acid based hydrogel formed from a gel injectate provide reduction of IOP sustained for at least 2 months, at least 3 months, at least 4 months or at least 6 months, and Gross established hyaluronic-acid based hydrogel formed from a liquid hydrogel precursor containing thiol-modified hyaluronan, and crosslinking agent containing a thiol-reactive crosslinking agent such as polyethylene glycol diacrylate (PEGDA), does not degrade until several months after gelation, thereby the chemically crosslinked hydrogel of Beckman in view of Gross would maintain its expanded shape for over an extended period of several months such as at least 2 months, at least 3 months, at least 4 months or at least 6 months so as to provide reduction of IOP sustained for at least 2 months, at least 3 months, at least 4 months or at least 6 months.
Regarding claim 18, as discussed above, Beckman teaches injecting a non-pharmacologically active formulation comprising a hyaluronic acid based hydrogel formed from a gel injectate, into a suprachoroidal space (SCS) of the eye (103 rejection, page 3 of this office action). Beckman teaches the injecting is a via a microneedle (Beckman: Abstract; [0006]-[0011], [0033]-[0046], [0055]-[0065]; claims 1-16, 26-44 and 53-56). Beckman teaches the non-pharmacologically active formulation comprising a hyaluronic acid based hydrogel formed from a gel injectate is expanded in the SCS (Beckman: claim 18). Gross teaches and provide the guidance for forming the hydrogel in situ by injecting the liquid hydrogel precursor solution (a gel injectate) at a site of interest in the eye and crosslinking of the liquid hydrogel precursor solution to form the chemically crosslinked hydrogel that is used for reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork (Gross: [0005]-[0022], [0026]-[0036], [0038]-[0048], [0099]-[0155], [0166], [0173]-[0195], [0200], [0207]-[0219], [0231]-[0232]). Thus, it would have been obvious to form the hydrogel of Beckman in view of Gross in the SCS in situ by using the liquid hydrogel precursor containing thiol-modified hyaluronan as taught in Gross and crosslinking said liquid hydrogel precursor (a gel injectate) by adding a crosslinking agent such as polyethylene glycol diacrylate (PEGDA) before, during or after the introduction of the liquid precursor solution into the location within the eye (i.e., SCS of Beckman) that can result in reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork. As such, it would have been obvious that the chemically crosslinked hydrogel of Beckman in view of Gross would expand in the SCS and solidifies within the SCS, as the resultant hydrogel is formed in situ within the SCS.
Regarding claim 19, as discussed above, Beckman teaches the needle is a microneedle.
Regarding claim 20, as discussed above, Beckman teaches injecting a non-pharmacologically active formulation comprising a hyaluronic acid based hydrogel formed from a gel injectate, into a suprachoroidal space (SCS) of the eye. Beckman teaches the injecting is a via a microneedle (Beckman: Abstract; [0006]-[0011], [0033]-[0046], [0055]-[0065]; claims 1-16, 26-44 and 53-56). Beckman teaches the non-pharmacologically active formulation comprising a hyaluronic acid based hydrogel formed from a gel injectate is expanded in the SCS (Beckman: claim 18). Gross teaches and provide the guidance for forming the hydrogel in situ by injecting the liquid hydrogel precursor solution (a gel injectate) at a site of interest in the eye and crosslinking of the liquid hydrogel precursor solution to form the chemically crosslinked hydrogel that is used for reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork (Gross: [0005]-[0022], [0026]-[0036], [0038]-[0048], [0099]-[0155], [0166], [0173]-[0195], [0200], [0207]-[0219], [0231]-[0232]). Thus, it would have been obvious to form the hydrogel of Beckman in view of Gross in the SCS in situ by using the liquid hydrogel precursor containing thiol-modified hyaluronan as taught in Gross and crosslinking said liquid hydrogel precursor (a gel injectate) by adding a crosslinking agent such as polyethylene glycol diacrylate (PEGDA) before, during or after the introduction of the liquid precursor solution into the location within the eye (i.e., SCS of Beckman) that can result in reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork. As such, it would have been obvious that the chemically crosslinked hydrogel of Beckman in view of Gross would solidifies within the SCS by gelation, as the resultant hydrogel is formed in situ within the SCS.
Regarding claim 21, Gross teaches and provides guidance for the hydrogel to be formed by crosslinking the liquid hydrogel precursor solution via UV radiation or heat ([0014]-[0017], [0181]-[0195]).
Regarding claim 22, Gross teaches and provides guidance for the hydrogel to be formed by crosslinking the liquid hydrogel precursor solution via change in pH or an ionic composition ([0014]-[0017], [0181]-[0195]).
Regarding claim 24, as discussed above, Beckman in view of Gross teaches chemically crosslinked hyaluronic acid-based hydrogel.
Regarding claim 25, as discussed above, Gross teaches and provide guidance for using a hyaluronic acid-based hydrogel formed from a liquid hydrogel precursor containing thiol-modified hyaluronan, and crosslinking agent containing a thiol-reactive crosslinking agent such as polyethylene glycol diacrylate (PEGDA).
Regarding claim 26, as discussed above, Gross teaches and provide guidance for using a hyaluronic acid-based hydrogel formed from a liquid hydrogel precursor containing thiol-modified hyaluronan, and crosslinking agent containing a thiol-reactive crosslinking agent such as polyethylene glycol diacrylate (PEGDA).
Regarding claims 50 and 53, Beckman teaches the non-pharmacologically active formulation comprising a hyaluronic acid based hydrogel formed from a gel injectate is expanded in the SCS (Beckman: claim 18). Beckman teaches the formulation provide reduction of IOP sustained for at least 2 months, at least 3 months, at least 4 months or at least 6 months (Beckman: [0009], [0044]; claim 7). Gross teaches hyaluronic-acid based hydrogel formed from a liquid hydrogel precursor containing thiol-modified hyaluronan, and crosslinking agent containing a thiol-reactive crosslinking agent such as polyethylene glycol diacrylate (PEGDA), wherein the hydrogel is tailored for long-term sustained release in which the hydrogel has a long life such that the hydrogel does not degrade for at least two years (Gross: [0013]-[0017], [0166]-[0195] and [0231]-[0232]). Thus, it would have been reasonably obvious that the chemically crosslinked hydrogel of Beckman in view of Gross would provide long-term sustained reduction of intraocular pressure for at least 180 days as recited in claim 50 and 53, respectively.
Regarding claims 51 and 54, as discussed above, Beckman in view of Gross teaches chemically crosslinked hyaluronic acid-based hydrogel.
Regarding claim 55, Gross teaches a method of increasing aqueous outflow of fluid through a trabecular meshwork, the method comprising before introducing the liquid hydrogel precursor solution into the location within the eye, the liquid hydrogel precursor solution is prepared by mixing two components (i.e., thiol-modified hyaluronan and crosslinking agent) and then introducing the liquid hydrogel precursor solution that was prepared by mixing the two components within three hours of mixing into the location within the eye during a medical procedure so as to form the hydrogel and leaving the hydrogel within the eye upon conclusion of the medical procedure (Gross: [0028]-[0030] and [0195]). Thus, the mixing of the two components as taught in Gross correlates to claimed “the hydrogel of the composition is partially crosslinked at the time of its introduction…,” as the mixing of the thiol-modified hyaluronan and crosslinking agent would provide some crosslinking but not full crosslinking such that the liquid hydrogel precursor solution can be introduced or injected at the location within the eye and then the formation of the resultant hydrogel after the introduction of the liquid hydrogel precursor solution within three hours of mixing of Gross would correlate to the claimed “undergoes further crosslinking after its introduction …” as the further crosslinking or gelation would need to occur in situ so that the resultant solid hydrogel can be formed. Thus, Gross renders obvious and provide guidance for preparing the gel injectate of Beckman by mixing two components (i.e., thiol-modified hyaluronan and crosslinking agent) and then introducing the liquid hydrogel precursor solution (the gel injectate) that was prepared by mixing the two components within three hours of mixing into the location within the eye (i.e., the SCS as guided by Beckman) during a medical procedure so as to form the hydrogel and leaving the hydrogel within the eye (i.e., the SCS as guided by Beckman) upon conclusion of the medical procedure so as to achieve reduction of intraocular pressure by increasing aqueous outflow of fluid through a trabecular meshwork, an objective that is common for both Beckman and Gross, and achieve Applicant’s claimed invention with reasonable expectation of success.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of Applicant’s invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 10/01/2025 have been fully considered but they are not persuasive.
Applicant argues that “Beckman does not teach or suggest a chemically crosslinked hydrogel or a gel that crosslinks at the time of, or following, its introduction into the eye.” (Remarks, pages 6-8).
In response, the Examiner disagrees. It is noted that the pending 103 rejection is based on the combined teachings of Beckman and Gross. Gross provided the guidance for use a chemically crosslinked hydrogel as the hydrogel material that is introduced in the suprachoroidal space (SCS) of the eye of Beckman.
As discussed above in the pending 103 rejection, it would have been obvious to one of ordinary skill in the art to use a chemically crosslinked hydrogel as the hydrogel material that is introduced in the suprachoroidal space (SCS) of the eye of Beckman by using the liquid hydrogel precursor containing thiol-modified hyaluronan as taught in Gross and crosslinking said liquid hydrogel precursor (a gel injectate) by adding a crosslinking agent such as polyethylene glycol diacrylate (PEGDA) before, during or after the introduction of the liquid precursor solution into the location within the eye that can result in reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork, and produce the claimed invention. One of ordinary skill in the art would have been motivated to do so because Beckman and Gross are commonly drawn to using crosslinked hyaluronic acid hydrogel for treating glaucoma by reducing intraocular pressure in the eye via increasing aqueous outflow of the trabecular meshwork, and Gross provided the guidance for using a chemically crosslinked hydrogel as the hydrogel material formed by crosslinking the liquid hydrogel precursor (a gel injectate) via adding a crosslinking agent such as polyethylene glycol diacrylate (PEGDA) before, during or after the introduction of the liquid precursor solution into the location within the eye so that the resultant chemically crosslinked hydrogel that is formed reduces intraocular pressure in the eye by increasing aqueous outflow of the trabecular meshwork, and such chemically crosslinked hyaluronic acid-based hydrogel is useful for reducing intraocular pressure to treat glaucoma for an extended period of time due to the hydrogel does not degrade until several months (Gross: [0013]-[0017], [0166]-[0195] and [0231]-[0232]). It is noted that the objective of Beckman is also to reducing intraocular pressure to treat glaucoma for an extended period of time (Beckman: Abstract; [0007], [0010], [0033]-[0034], [0036], [0041], [0043]-[0044]; claims 1-5, 11 and 29-38). Thus, an ordinary artisan seeking to sustain the reduction of intraocular pressure for an extended period of time, would have looked to using a chemically crosslinked hydrogel as the hydrogel material that is introduced in the suprachoroidal space (SCS) of the eye of Beckman by using the liquid hydrogel precursor containing thiol-modified hyaluronan as taught in Gross and crosslinking said liquid hydrogel precursor (a gel injectate) by adding a crosslinking agent such as polyethylene glycol diacrylate (PEGDA) before, during or after the introduction of the liquid precursor solution into the location within the eye that can result in reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork, and achieve Applicant’s claimed invention with reasonable expectation of success.
Applicant argues that “[a]s described in Applicant's Example 1, Applicant therefore injected Juvederm®, which is a HA-based hydrogel that includes chemical crosslinks, into the SCS of the eye, and IOP was reduced for 35 days-almost three times longer than when using Healon® that lacked chemical crosslinks.” Applicant goes on to indicate that “Applicant then created and tested a new hydrogel formulation with even more chemical crosslinking, as described in Examples 2-6” and [t]he HA-XL formulation provided IOP reduction for 4 months, which was almost four times longer than Juvederm® and about 10 times longer than Healon®.” Thus, Applicant alleges that “[n]othing in Beckman remotely suggested chemical crosslinking of a gel could produce a longer lasting IOP reduction, and certainly not an improvement of the magnitude demonstrated by Applicant.” (Remarks, page 8, paragraphs 2-5).
In response, the Examiner disagrees. Applicant’s data from Examples 1-6 of the specification are considered, but found insufficient to obviate the pending 103 rejection over the combined teachings of Beckman and Gross. This is because Beckman allows for tailoring of the gel injectate such that the hydrogel formed in the SCS can reduce intraocular pressure for as long as for at least 6 months or longer than a year. As discussed above in the pending 103 rejection, Gross teaches hyaluronic-acid based hydrogel formed from a liquid hydrogel precursor containing thiol-modified hyaluronan, and crosslinking agent containing a thiol-reactive crosslinking agent such as polyethylene glycol diacrylate (PEGDA), wherein the hydrogel is tailored for long-term sustained release in which the hydrogel has a long life such that the hydrogel does not degrade for at least two years (Gross: [0013]-[0017], [0173]-[0195] and [0231]-[0232]). Thus, Gross provides the guidance and expectation that the use of a chemically crosslinked hydrogel as the hydrogel material of Beckman would provide long lasting intraocular pressure reduction because hyaluronic-acid based hydrogel formed from a liquid hydrogel precursor containing thiol-modified hyaluronan, and crosslinking agent containing a thiol-reactive crosslinking agent such as polyethylene glycol diacrylate (PEGDA) per Gross has a long life such that the hydrogel does not degrade for at least two years, thereby providing long lasting or sustained reduction of intraocular pressure, which as discussed above, is also an objective of Beckman, to provide sustained reduction of intraocular pressure for a period of at least 6 months or longer than a year (Beckman: Abstract; [0007], [0010], [0033]-[0034], [0036], [0041], [0043]-[0044]; claims 1-5, 11 and 29-38). Thus, the use of a chemically crosslinked hydrogel for long lasting reduction of intraocular pressure in the treatment of glaucoma by increasing aqueous outflow of the trabecular meshwork is an obvious and expected result, irrespective of the location of interest within in the eye (i.e., suprachoroidal space (SCS) vs. Schlemm's canal) to which the chemically crosslinked hydrogel is introduced.
Applicant argues “Gross does not disclose or suggest introducing a chemically cross-linked hydrogel into a suprachoroidal space of a patient's eye.” Applicant alleges “[t]he treatment method of Gross is highly specific to the Schlemm's canal, which differs in many anatomical and physiological ways from the suprachoroidal space, and one of ordinary skill in the art would not have had any reasonable expectation that these methods could be combined with those of Beckman to derive the methods recited by Applicant's claims.” (Remarks, page 8, last paragraph to page 9, 1st paragraph).
In response, the Examiner disagrees. To the extent Gross location of introducing the hydrogel is into the Schlemm's canal of the eye, the introduction of a hydrogel into a suprachoroidal space of the eye has been taught by Beckman (see 103 rejection, page 3 of this office action). Gross was used for teaching and providing guidance on using a chemically crosslinked hydrogel as the hydrogel material of Beckman by using the liquid hydrogel precursor containing thiol-modified hyaluronan as taught in Gross and crosslinking said liquid hydrogel precursor (a gel injectate) by adding a crosslinking agent such as polyethylene glycol diacrylate (PEGDA) before, during or after the introduction of the liquid precursor solution into the location within the eye that can result in reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork (see 103 rejection, pages 4-6 of this office action), which as discussed above in the 103 rejection, is the common objective for Beckman and Gross (see 103 rejection, pages 3-6 of this office action), to reduce intraocular pressure by increasing aqueous outflow of the trabecular meshwork.
Accordingly, Beckman and Gross are properly combined to render obvious Applicant’s claimed method for reducing intraocular pressure.
Applicant argues “the methods of Gross are completely different from those described in Beckman” and thus, “one of ordinary skill in the art would not have had any reason to look to Gross for its teaching in situ crosslinking in the eye. There would not have been any reasonable expectation, in view of the numerous and significant differences between the treatment methods, that Gross's methods in the Schlemm's canal could or should be adapted to Beckman's methods, certainly not in a manner to that would reasonably be predicted to result in Applicant's claimed method where intraocular pressure is reduced over a period of 30 days or more.” Applicant alleges that “one of ordinary skill in the art, seeking to improve upon the methods of Beckman, would not have consulted Gross at least because (i) Gross is not concerned with methods of treating intraocular pressure by administering hydrogels to the suprachoroidal space, (ii) Gross does not disclose or suggest introducing hydrogels, that are already chemically cross-linked, into the eye, and (iii) Gross seeks to alter flow via the conventional pathway in contrast to Beckman which seeks to alter flow via an unconventional pathway.” Thus, Applicant alleges “[o]ne of ordinary skill in the art therefore would not have had a reason to combine them and derive Applicant's claimed methods.” (Remarks, page 9, 2nd paragraph through page 10).
In response, the Examiner disagrees. As discussed above, to the extent Gross location of introducing the hydrogel is into the Schlemm's canal of the eye, the introduction of a hydrogel into a suprachoroidal space of the eye has been taught by Beckman (see 103 rejection, page 3 of this office action). Gross was used for teaching and providing guidance on using a chemically crosslinked hydrogel as the hydrogel material of Beckman by using the liquid hydrogel precursor containing thiol-modified hyaluronan as taught in Gross and crosslinking said liquid hydrogel precursor (a gel injectate) by adding a crosslinking agent such as polyethylene glycol diacrylate (PEGDA) before, during or after the introduction of the liquid precursor solution into the location within the eye that can result in reduction of intraocular pressure by increasing aqueous outflow of the trabecular meshwork (see 103 rejection, pages 4-6 of this office action), which as discussed above in the 103 rejection, is the common objective for Beckman and Gross (see 103 rejection, pages 3-6 of this office action), to reduce intraocular pressure by increasing aqueous outflow of the trabecular meshwork.
Furthermore, as discussed above, Beckman allows for tailoring of the gel injectate such that the hydrogel formed in the SCS can reduce intraocular pressure for as long as for at least 6 months or longer than a year. As discussed above, Gross teaches hyaluronic-acid based hydrogel formed from a liquid hydrogel precursor containing thiol-modified hyaluronan, and crosslinking agent containing a thiol-reactive crosslinking agent such as polyethylene glycol diacrylate (PEGDA), wherein the hydrogel is tailored for long-term sustained release in which the hydrogel has a long life such that the hydrogel does not degrade for at least two years (Gross: [0013]-[0017], [0173]-[0195] and [0231]-[0232]). Thus, Gross provides the guidance and expectation that the use of a chemically crosslinked hydrogel as the hydrogel material of Beckman would provide long lasting intraocular pressure reduction because hyaluronic-acid based hydrogel formed from a liquid hydrogel precursor containing thiol-modified hyaluronan, and crosslinking agent containing a thiol-reactive crosslinking agent such as polyethylene glycol diacrylate (PEGDA) per Gross has a long life such that the hydrogel does not degrade for at least two years (Gross: [0013]-[0017], [0173]-[0195] and [0231]-[0232]), thereby providing long lasting or sustained reduction of intraocular pressure, which as discussed above, is also an objective of Beckman, to provide sustained reduction of intraocular pressure for a period of at least 6 months or longer than a year (Beckman: Abstract; [0007], [0010], [0033]-[0034], [0036], [0041], [0043]-[0044]; claims 1-5, 11 and 29-38). Thus, the use of a chemically crosslinked hydrogel for long lasting reduction of intraocular pressure in the treatment of glaucoma by increasing aqueous outflow of the trabecular meshwork is an obvious and expected result, irrespective of the location of interest within in the eye (i.e., suprachoroidal space (SCS) vs. Schlemm's canal) to which the chemically crosslinked hydrogel is introduced.
Accordingly, Beckman and Gross are properly combined to render obvious Applicant’s claimed method for reducing intraocular pressure.
As a result, for at least the reasons discussed above, claims 1-3, 5-8, 11-14, 18-22, 24-26, and 49-55 remain obvious and unpatentable over the combined teachings of Beckman and Gross in the pending 103 rejection as set forth in this office action.
New Rejections
Necessitated by Applicant’s Claim Amendments
Claim Rejections - 35 USC § 112 – NEW MATTER
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 49-55 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 49 introduce new matter as the claim recites the limitation: “the composition, before its introduction into the SCS of the eye of the patient, comprises a chemically cross-linked hydrogel.”
Claim 52 introduce new matter as the claim recites the limitation: “the composition comprises a hydrogel that undergoes a chemical or physical crosslinking at the time of, or following, its introduction into the SCS of the eye of the patient.”
Claim 55 introduce new matter as the claim recites the limitation: “the hydrogel of the composition is partially crosslinked at the time of its introduction into the SCS of the eye of the patient and then undergoes further crosslinking after its introduction into the SCS of the eye of the patient.”
There is no support in the specification for said limitations of claims 49, 52 and 55. Applicant asserted that the support for the amendments can be found throughout Applicant’s original application (specification).
However, after a thorough review of specification, there appeared to be no support or disclosure anywhere in the specification for the breadth of “before its introduction into the SCS of the eye of the patient” of claim 49, “a hydrogel that undergoes a chemical or physical crosslinking at the time of, or following, its introduction into the SCS of the eye of the patient” of claim 52, and “the hydrogel of the composition is partially crosslinked at the time of its introduction into the SCS of the eye of the patient and then undergoes further crosslinking after its introduction into the SCS of the eye of the patient” of claim 55. MPEP §2163.06 states: “Applicant should therefore specifically point out the support for any amendments made to the disclosure.”
Claims 50-51 and 53-54 are also rejected, as they dependent directly or indirectly from claims 49 and 52, respectively, thereby also containing the conflicting new matter limitations.
As such, the disclosure does not reasonably convey that the inventor had possession of the subject matter of 49, 52 and 55 at the time of filing of the instant application.
Claim Rejections - 35 USC § 112
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 21 and 22 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.
Claims 21 and 22 are not further limiting from claim 1, to which claims 21 and 22 indirectly depend from. It is noted that claim 1 recites the SCS comprises a chemically cross-linked hydrogel. However, gelation by ultrasound or heat as recited in claim 21 is not a chemical crosslinking, but rather physical crosslinking. In the same context, gelation by a change in pH, ionic composition or by contact with biological fluids within SCS as recited in claim 22 is not a chemical crosslinking, but rather physical crosslinking.
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.
Conclusion
No claim is allowed.
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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/DOAN T PHAN/ Primary Examiner, Art Unit 1613