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 .
DETAILED ACTION
Claims 1-20 are pending and under consideration.
The rejection of claims 1-4, 6, 11-14 and 16 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-6, 8, 11, 12, 14-16, and 18 of U.S. Patent No. 11,878,051 is withdrawn in light the terminal disclaimer filed on 04/29/2026.
The rejection of claims 1-7, 10-17, and 20 on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 10, 11-17, and 20 of U.S. Patent No. 11,890,331 is withdrawn in light the terminal disclaimer filed on 04/29/2026.
Response to Arguments
Applicant's arguments, see the remarks p. 6 para. 1, filed 04/29/2026, with respect to rejection of claims 6 and 16 under 35 U.S.C. §112(b) for the term of approximation, “about”, have been fully considered and are persuasive. The §112(b) of claims 6 and 16 has been withdrawn.
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.
Claims 1-6, 10-17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al., (Effectiveness of Retrobulbar Hyaluronidase Injection in an Iatrogenic Blindness Rabbit Model Using Hyaluronic Acid Filler Injection. Plast Reconstr Surg. 2019 Jul;144(1):137-143; cited in the IDS filed 03/07/2025) in view of Prausnitz et al., (US2018/0028357A1; cited in the IDS filed 03/07/2025).
Regarding claim 1, Lee teaches a method of treating hyaluronic-induced retinal artery occlusion (p. 138, col. 1, Retinal Artery Inclusion Model), i.e., hyaluronic acid-induced blood vessel blockage, in rabbits comprising administering 1,500 IU/mL of hyaluronidase, and in a subsequent study, 2 ml of 3000 IU hyaluronidase was injected into the retrobulbar area (p. 138, col. 2, Retrobulbar Hyaluronidase Injection). Although the concentration of Lee differs from that of the instant claim, MPEP§ 2144.05 II states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.")”. The selection of specific hyaluronidase concentrations would have been a matter of routine optimization on the part of the artisan of ordinary skill, said artisan recognizing that hyaluronidase concentration would affect the level of hyaluronic acid degradation.
Lee does not teach that the hyaluronidase was administered to a suprachoroidal space of the eye.
However, Prausnitz teaches methods for targeted administration of a drug to a patient’s eye, comprising inserting a hollow microneedle into the sclera of the eye into the suprachoroidal space of the eye (Abstract). In one embodiment, the fluid drug formulation further includes an agent effective to degrade collagen or GAG fibers in the sclera, which may enhance penetration/release of the drug into the ocular tissues. This agent may be, for example, an enzyme, such a hyaluronidase [0086].
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to modify Lee’s method by replacing the site of administering hyaluronidase from retrobulbar in the eye of a rabbit to the suprachoroidal space of the eye of a patient, as taught by Prausnitz. One of ordinary skill would have been motivated to do so because Prausnitz teaches that an enzyme, such as hyaluronidase, may be administered in combination with a drug formulation (para. [0086]. One of ordinary skill in the art would have had a reasonable expectation of success because Lee and Prausnitz are in the same field of endeavor of ocular drug (hyaluronidase) delivery.
Regarding claims 2-5, Lee teaches a hyaluronidase concentration of 1,500 IU/mL (p. 138, col. 2, Retrobulbar Hyaluronidase Injection). Lee does not teach the hyaluronidase concentrations of the instant claims, however, as stated, generally concentrations and temperature will not affect patentability as it is not inventive to discover the optimum or workable ranges by routine experimentation.
Regarding claim 6, Lee teaches administration of the hyaluronidase composition at a volume of 2 mL (p. 138, col. 2, Retrobulbar Hyaluronidase Injection). Although the volume of Lee is different than that of the instant claim, it is not inventive to discover the optimum or workable ranges by routine experimentation, as stated.
Regarding claim 10, Lee teaches that the hyaluronidase was administered with saline (p. 138, col. 2, Retrobulbar Hyaluronidase Injection), which is considered an agent.
Regarding claim 11, Lee teaches a method of treating hyaluronic-induced retinal artery occlusion (p. 138, col. 1, Retinal Artery Inclusion Model), i.e., vascular occlusion, in rabbits comprising administering 1,500 IU/mL of hyaluronidase (p. 138, col. 2, Retrobulbar Hyaluronidase Injection). Although the concentration of Lee differs from that of the instant claim, MPEP§ 2144.05 II states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.")”. The selection of specific hyaluronidase concentrations would have been a matter of routine optimization on the part of the artisan of ordinary skill, said artisan recognizing that hyaluronidase concentration would affect the level of hyaluronic acid degradation.
Lee does not teach that the hyaluronidase was administered to a suprachoroidal space of the eye.
However, Prausnitz teaches methods for targeted administration of a drug to a patient’s eye, comprising inserting a hollow microneedle into the sclera of the eye into the suprachoroidal space of the eye (Abstract). In one embodiment, the fluid drug formulation further includes an agent effective to degrade collagen or GAG fibers in the sclera, which may enhance penetration/release of the drug into the ocular tissues. This agent may be, for example, an enzyme, such a hyaluronidase [0086].
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to modify Lee’s method by replacing the site of administering hyaluronidase from retrobulbar in the eye of a rabbit with the suprachoroidal space of the eye of a patient, as taught by Prausnitz. One of ordinary skill would have been motivated to do so because Prausnitz teaches that an enzyme, such as hyaluronidase, may be administered in combination with a drug formulation (para. [0086]. One of ordinary skill in the art would have had a reasonable expectation of success because Lee and Prausnitz are in the same field of endeavor of ocular drug delivery.
Regarding claims 12-15 and 17, Lee teaches administration of a single dose of hyaluronidase at a concentration of 1,500 IU/mL (p. 138, col. 2, Retrobulbar Hyaluronidase Injection). Lee does not teach the hyaluronidase concentrations of the instant claims, however, as stated, generally concentrations and temperature will not affect patentability as it is not inventive to discover the optimum or workable ranges by routine experimentation.
Regarding claim 16, Lee teaches administration of the hyaluronidase composition at a volume of 2 mL (p. 138, col. 2, Retrobulbar Hyaluronidase Injection). Although the volume of Lee is different than that of the instant claim, it is not inventive to discover the optimum or workable ranges by routine experimentation.’
Regarding claim 20, Lee teaches that the hyaluronidase was administered with saline (p. 138, col. 2, Retrobulbar Hyaluronidase Injection), which is considered an agent.
Claims 7-9, 18, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al., (Effectiveness of Retrobulbar Hyaluronidase Injection in an Iatrogenic Blindness Rabbit Model Using Hyaluronic Acid Filler Injection. Plast Reconstr Surg. 2019 Jul;144(1):137-143) and Prausnitz et al., (US2018/0028357A1) as applied to claims 1 and 11 above, and further in view of DeLorenzi., (New High Dose Pulsed Hyaluronidase Protocol for Hyaluronic Acid Filler Vascular Adverse Events. Aesthet Surg J. 2017 Jul 1;37(7):814-825; cited in the IDS filed 03/07/2025).
See discussion of Lee and Prausnitz above, which is incorporated into this rejection as well.
Regarding claims 7, 8, and 18, DeLorenzi teaches a method of reducing hyaluronic-acid vascular obstruction comprising administering three to four treatments of hyaluronidase to ischemic, i.e., obstructed, area (Abstract; p. 825, col 1., para. 1).
Regarding claims 9 and 19, DeLorenzi teaches the administration of hyaluronidase every hour to 90 minutes (p. 824, col. 2, para. 3). Although this time period between hyaluronidase administration differs from that of the instant claim, selection of specific dosage times would have been a routine matter of optimization on the part of the artisan of ordinary skill, said artisan recognizing that time between hyaluronidase administration would affect rate of hyaluronic acid degradation.
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to further modify the method of administering hyaluronidase to the suprachoroidal space of the eye, as taught by Lee as modified by Prausnitz, by administering at repeated intervals, as taught by DeLorenzi. One of ordinary skill in the art would have been motivated to do so because DeLorenzi teaches that repeated hyaluronidase administration is based on the hypothesis that flooding occluded blood vessels with a sufficient concentration of hyaluronidase allows for the hyaluronic acid to dissolve to the point where the products of hydrolysis can pass through capillary beds (Abstract). One of ordinary skill in the art would have had a reasonable expectation of success because Lee, Prausnitz, and DeLorenzi are in the same field of endeavor of reducing hyaluronic-acid vascular obstruction using hyaluronidase administration methods.
Response to Arguments
Applicant's arguments filed 04/29/2026 have been fully considered but they are not persuasive.
Rejection of claims 1-6, 10-17, and 20 under 35 U.S.C. 103 over in view of Prausnitz
Applicant argues that Lee discusses the rationale behind the treatment of injecting hyaluronidase into the retrobulbar space is to reverse the ischemic course of the ophthalmic artery, retinal artery, posterior ciliary artery, and the arteries of the optic nerve through the retrobulbar space on the basis that it was previously shown that hyaluronidase can diffuse into the obstructed vessels and degrade the hyaluronic acid filler. See the remarks p.7 para. 2. Prausnitz states that its disclosed method includes inserting a hollow microneedle into the sclera of the eye at an insertion site and infusing over a period of time a fluid drug formulation through the inserted microneedle and into the suprachoroidal space of the eye (Prausnitz abstract). See the remarks the paragraph spanning pgs. 7-8. Lee and Prausnitz do not teach or suggest a composition comprising at least 8,000 IU/mL of a hyaluronidase administered to a suprachoroidal space of the eye in a manner that reduces or eliminates a hyaluronic acid-induced blockage in one or more blood vessels supplying blood to an eye. Lee teaches 3,000 IU diluted in 2 mL of saline was effective in blood flow reperfusion, and restoration of retinal functionality as assessed from ERG readings. This equates to no more than 1,500 IU/mL of hyaluronidase administered to a retrobulbar space of the eye socket. See the remarks p. 9 para. 2. Applicant asserts that arriving at a hyaluronidase concentration of at least 8,000 IU/mL is not merely routine optimization, because one of ordinary skill in the art would not recognize the claimed limitation “at least 8,000 IU/mL to a suprachoroidal space of the eye” as a result-effective variable. See the remarks p. 9 para. 3. Changing the route of administration from the retrobulbar as disclosed in Lee to the presently claimed suprachoroidal space is not a result effective variable which can be arrived at as a matter of routine optimization. See the remarks the paragraph spanning pgs. 9-10.
This argument is not persuasive, because MPEP 2144.05(II)(A) indicates that differences in concentration or temperature generally amount to “routine optimization” and will not support patentability unless there is evidence indicating the claimed feature is critical. Lee teaches administering 1,500 IU/mL of hyaluronidase into the retrobulbar area in the eye of a rabbit (p. 138, col. 2). Applicant has not set forth evidence indicating that the claimed at least 8,000 IU/mL concentration is critical. Therefore, the fact that applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Furthermore, Prausnitz teaches explicitly teaches “inserting a hollow microneedle into the sclera of the eye at an insertion site and infusing a fluid drug formulation through the inserted microneedle and into the suprachoroidal space of the eye, wherein the infused fluid drug formulation flows within the suprachoroidal space away from the insertion site during the infusion” (abstract). Therefore, contrary to Applicant’s argument, the rationale set forth above does not rely on routine optimization to meet the suprachoroidal space claim element, because Prausnitz explicitly teaches that element.
Applicant argues that the retrobulbar space is a large cavity in the back of the eye that has direct access to the central retinal artery. Injection into the retrobulbar space allows the hyaluronidase enzyme to diffuse through the arterial wall and degrade the hyaluronic acid blockage of obstructive vessels. However, a suprachoroidal administration does not rely on diffusion of hyaluronidase into the central retinal artery. Instead, this route of administration is a very small space that relies on the proximity of the suprachoroidal space to the site of the hyaluronic acid blockage. Thus, the space differences as well as the delivery means are different between Lee and the presently claimed methods, and these unknown variables would affect the effectiveness of the hyaluronidase activity. See the remarks p. 10 para. 1. Applicant asserts that the effects of hyaluronidase on the administration site differ. A person skilled in the art would intuitively understand that increasing the concentration of hyaluronidase would result in increased digestion of this enzyme’s substrates. See the remarks p. 10 last passage. Furthermore, Applicant argues that Lee and Prausnitz do not render the claimed subject matter obvious because there is no predictable results or reasonable expectation of success. See the remarks p. 15 para. 1.
This argument is not persuasive because Prausnitz, not Lee, is relied upon for teaching the suprachoroidal space claim element. The central retinal artery supplies blood to the eye. Lee teaches a hyaluronic-induced retinal artery occlusion (p. 138, col. 1), i.e. a hyaluronic acid-induced blockage in one or more blood vessels supplying blood to an eye. Lee teaches an administration into the retrobulbar area (p. 138, col. 2), which is posterior area of the eye. Prausnitz states that upon entering the suprachoroidal space the fluid drug formulation flows circumferentially from the insertion site toward the retinochoroidal tissue, macula, and optic nerve in the posterior segment of the eye ([0030]). Applicant indicates that the suprachoroidal administration route relies on the proximity of the suprachoroidal space to the site of the hyaluronic acid blockage. However, the instant claims do not limit the specific site of the hyaluronic acid blockage because the instant claims do not limit the one or more blood vessels that are blocked due to the hyaluronic acid-induced blockage. Thus, there is no evidence of record that suggests that replacing Lee’s retrobulbar administration site with Prausnitz’s suprachoroidal site would be inoperable. Rather, the evidence of record set forth in the instant specification suggests that hyaluronidase can be administered to the suprachoroidal space of an eye with a hyaluronic acid-induced blockage in the central retinal artery. See [0164] of the instant spec.
Applicant argues that the optimal concentration of hyaluronidase to be administered in the suprachoroidal space is known in the art to be 120 IU/mL to 130 IU/mL. Although Prausnitz did not disclose the amount of hyaluronidase to administer, other references indicate that from 7.2 IU/mL to 438 IU/mL is an effective concentration as a penetration/release agent. For example, two clinical trials by Thomas indicate that 150 IU/mL of recombinant human hyaluronidase (rHuPH20) was effective as a penetration/release agent, in Thomas I, this Phase IIIB study compared pharmacokinetics, safety, and tolerability of morphine administration subcutaneously with and without 150 IU/mL of rHuPH20 as compared to intravenously administered morphine and found hyaluronidase to enhance the absorption rate of morphine and significantly reduce the mean Tmax. See the remarks p. 11 para. 1.
This argument is not persuasive because the study of Thomas (citation no. 27 in the IDS filed 03/07/2025) concerning the subcutaneous administration of morphine with and without rHuPH20 is not germane to the instant rejection set forth above. The instant claims do not limit the hyaluronidase to recombinant human hyaluronidase, nor do the claims require the hyaluronidase to be administered with morphine. Although Thomas teaches eye pain in table 3 on page 679, Thomas does not teach individuals that need a reduction or elimination of a hyaluronic acid-induced blockage in one or more blood vessels supplying blood to an eye. Therefore, to the extent that Applicant is arguing that the claimed administration of at least 8,000 IU/mL is critical in view of the teachings of Thomas, it is unpersuasive because the teachings of Thomas are not germane to the instant invention.
Applicant argues that Vaughn discloses a Phase I clinical study pharmacokinetics and glucodynamics of a rapid-acting analog insulin (lispro, Humalog) or regular human insulin (Humulin) administered with or without 240 IU/mL of recombinant human hyaluronidase (rHuPH20), concluding that coadministration of rHuPH20 as a penetration/release agent accelerated the PK and glucodynamics of both insulin formulations. See the remarks the paragraph spanning pgs. 11-12. Likewise, Marrow [sic. Morrow] discloses a Phase I clinical study to compare the pharmacokinetics and glucodynamics of three rapid-acting insulin analogs injected subcutaneously with or without 5 µg/mL (approximately 120 IU/mL to 130 IU/mL) of rHuPH20 as a penetration/release agent. See the remarks p. 12 para. 1. Muchmore summarizes the findings of eight clinical studies which demonstrate that coadministration of hyaluronidase as a penetration/release agent accelerated insulin absorption and action, improved postprandial glycemic excursions, reduced hypoglycemia risks, reduced intrasubject variability of insulin absorption and action and provided greater consistency in absorption action provides. Table 1 of Muchmore teaches rHuPH20 concentrations from 0.3 µg/mL to 18.2 µg/mL (approximately 7.2 IU/mL to 483 IU/mL). See the remarks p. 12 para. 2.
This argument is not persuasive because the instant claims do not require the hyaluronidase to function as a penetration/release agent in combination with insulin. As such, Vaughn, Morrow, and Muchmore (citation numbers 30, 19 and 21 in the IDS filed 03/07/2025 respectively) do not provide evidence that the claimed concentration of at least 8000 IU/mL is critical for the claimed purpose of reducing or eliminating a hyaluronic acid-induced blockage in one or more blood vessels supplying blood to an eye. Rather, the concentrations taught by Vaughn, Morrow and Muchmore are relevant to the use of hyaluronidase in combination with insulin.
Applicant asserts that Prausnitz teaches that 200 IU/mL of hyaluronidase is effective as a penetration/release agent. Applicant cites Valeant to assert that VITRASE is a hyaluronidase approved by FDA for intraocular administration up to a concentration of 200 IU/mL, while a second hyaluronidase, HYLENEX, was approved for intraocular administration in a range of 30-300 IU/mL. See the remarks the paragraph bridging pgs 12-13. Applicant argues that Prausnitz teaches a wide range of drugs that may be formulated for delivery to ocular tissues. Applicant asserts that Prausnitz is silent as to any specific concentration of any of the disclosed drugs that should be administered to the suprachoroidal space. See the remarks p. 13 para. 1. Thus, Applicant asserts that at best Prausnitz teaches that hyaluronidase was useful as a penetration/release agent for other drugs administered to retinochorodial tissue, macula, and optic nerve. See the remarks p. 13 para. 2.
This argument is not persuasive because Lee, not Prausnitz, is relied upon for teaching an administration of 1,500 IU/mL of hyaluronidase (p. 138, col. 2), and MPEP 2144.05(II)(A) indicates that differences in concentration or temperature generally amount to “routine optimization” and will not support patentability unless there is evidence indicating the claimed feature is critical.
Applicant argues Lee was criticized by contemporaries and to date there is no published report demonstrating the successful repeat of Lee’s experiments. See the remarks p. 15 last passage. For example, Hwang published a commentary on Lee indicating that the observed blood flow reperfusion and restoration of retinal functionality in some of the test animals could simply have been through clearance by the circulatory system and not at all due to the effectiveness of retrobulbar administration of hyaluronidase. A commentary by Silkiss (citation no. 26 in the IDS filed 03/07/2025)supports this interpretation given their comments that not all patients that present with decreased vision will have an ischemic event and that those that do, a small percentage will recover without intervention. See the remarks p. 16 para. 1. Additionally, Applicant asserts that Hwang indicated that the study in Lee reported reversal of branch retinal artery occlusion but not central retinal artery occlusion, which Hwang (citation no. 13 of the IDS filed 03/07/2025) stressed was an important distinction. See the remarks p. 16 para. 2.
This argument is not persuasive because MPEP 2123 states that “[a] reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art”. Lee teaches the active method step of administering hyaluronidase to the eye of an individual with a hyaluronic acid-induced blockage in one or more blood vessels supplying blood to the eye. The instant claims do not limit the one or more blood vessels to any particular artery, such as the central retinal artery. Therefore, Applicant’s argument that the study of Lee does not reverse central retinal artery occlusion is not persuasive.
Applicant argues that Zhu evaluates the efficiency of retrobulbar hyaluronidase injection as a rescue treatment for vision loss caused by HA filler embolization. Zhu teaches patients with branch retinal artery occlusion and/or posterior ischemic optic neuropathy, or ophthalmic artery occlusion. Zhu teaches treating patients with 750 IU/mL or 15,00 IU/mL. Zhu indicates that no patient demonstrated substantial retinal artery recanalization or vision acuity improvement after treatment. See the remarks p.17 para 1.
This argument is not persuasive because Zhu (citation no. 34 in the IDS filed 03/07/2025) is not relied upon for teaching the instantly claimed administration step. Lee is relied upon for teaching the active method step of administering hyaluronidase to the eye of an individual in need. Lee teaches an administration to the retrobulbar area of the eye, which is the same area taught by Zhu. However, the instant claims require administration to the suprachoroidal space of the eye. Prausnitz is relied upon for teaching that claim element. Therefore, the fact that applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Rejection of claims 7-9, 18, and 19 under 35 U.S.C. 103 over Lee, Prausnitz and DeLorenzi
Applicant argues that DeLorenzi specifically states that hyaluronidase administration would be ineffective in treating filler-associated blindness. DeLorenzi indicates that very small doses of hyaluronidase are effective in the nonemergency situation of removing small amounts of unwanted filler slowly, in the critical situation of filler-associated blindness, increased reaction rate of higher doses are likely to be insufficient. See the remarks p. 18 first passage.
This argument is not persuasive because it is not commensurate in scope with the instant claims. The instant claims do not require the individual to be in need of filler-associated blindness.
Applicant argues that several reviews, including that of Papp and Navarro-Hernandez (citation numbers 24 and 22 of the IDS filed 03/07/2025 respectively), have been published after Lee, all questioning the efficacy of retrobulbar administration of hyaluronidase.
This argument is not persuasive because Prausnitz is relied upon for teaching an administration to the suprachoroidal space of an eye. As such, the rationale discussed above does not rely on Lee’s retrobulbar administration.
Applicant argues that experts in the field challenge the veracity of the results reported in Lee, and questioned the usefulness of hyaluronidase as a realistic treatment for HA-associated vascular occlusion in the eye. Thus, there was no reasonable expectation of success that administration of hyaluronidase in the suprachoroidal space would result in degradation of a HA-associated vascular occlusion in the eye given the questionable and uncertain efficacy of retrobulbar administration of hyaluronidase. See the remarks p. 19 para. 1. Applicant asserts that there was no reasonable expectation of success that suprachoroidal administration of hyaluronidase would result in degradation of a HA blockage in the arteries of the eye and thus be viable therapy for HA-associated vascular occlusion in the eye. See the remarks p. 19 para. 2. Applicant argues that for a hyaluronidase treatment to be effective, a person of ordinary skill would presume that 1) a suitable administration route would need to reach the main trunks of these arteries; and 2) the enzyme would need to quickly reach the blockage site in the main trunk of one of these arteries given that the half-life of hyaluronidase in blood is very short. See the remarks the paragraph bridging pgs. 22-23. Applicant asserts that suprachoroidal administration is counterintuitive. See the remarks p. 23 last passage. A person of ordinary skill would expect only a fraction of hyaluronidase to reach ophthalmic artery and then the central retinal artery as well as the long and short posterior ciliary arteries; and such fraction would completely degrade in blood before reaching the main trunks of central retinal artery. See the remarks p. 24. Applicant argues that hyaluronidase concentrations above 483 could be harmful to a patient’s eye. See the remarks p. 28 first passage.
This argument is not persuasive because a reference is presumed to be operable until applicant provides facts rebutting the presumption of operability. See MPEP 2121. In the instant case, Lee states “hyaluronidase can diffuse into the obstructed vessels and degrade the hyaluronic acid filler”. See p. 141 left col. The instant claims are drawn a method of reducing or eliminating a hyaluronic acid-induced blockage (claim 1 lines 1-2), or a method of reducing or inhibiting a vascular occlusion in an eye (claim 11 lines 1-2). Therefore, the claims encompass any reduction in a hyaluronic acid-induced blockage or vascular occlusion.
Applicant argues that the instant specification teaches, in example 1, a suprachoroidal administration of 2,400 IU/mL of hyaluronidase reverses HA polymer associated vascular occlusion in the retinal. Day 3 post-induction, all animals showed significant blood flow and neuronal activity in the retina thereby illustrating a significant recovery. See the remarks p. 26 last passage.
This argument is not persuasive because it is not commensurate in scope with the instant claims. The instant claims do not require significant blood flow or neuronal activity in the retina to be recovered. Rather, the claims encompass any reduction in a hyaluronic acid-induced blockage or vascular occlusion.
Conclusion
THIS ACTION IS MADE FINAL. 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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/K.C.B./Examiner, Art Unit 1657
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