DETAILED 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 .
Claim Status
Applicant’s submission filed 03/23/2026 has been received and entered. Claims 104, 105, 113-115, 124 and 126 have been amended. Claims 106 and 114-126 remain withdrawn as being directed to un-elected inventions. Accordingly, claims 104-105 and 107-113 are pending and under current examination.
Status of Prior Rejection/Response to Arguments
The objection to drawing is withdrawn:
Applicant’s submission of the replacement sheets of drawing obviates the current objection on record. The objection is withdrawn.
The objection to claim 104 is withdrawn:
Applicant’s amendment to claim 104 obviates the current objection on record. The objection is withdrawn.
The rejection to claims 104, 105, 109 and 110 under 35 U.S.C. §102(a)(1) over Kumru et al., evidenced by Aidoo et al. is withdrawn:
The rejection to claims 104, 105, 109 and 111-113 under 35 U.S.C. §102(a)(1) and 102(a)(2) over Young is withdrawn:
Applicant’s amendment to claim 1 adds the limitation ”the formulation comprises about 0.01 ng/mL to about 1 mg/mL sodium hyaluronate”. This limitation is not taught by Kumru et al., Aidoo et al., as well as Young, therefore the amendment is effective to obviate the prior basis of the rejection. The rejection is withdrawn.
The rejection to claims 104-105 and 107-113 under 35 U.S.C. §103 over Young in view of Burke et al, as evidenced by Huberlant is withdrawn:
Applicant’s amendment to claim 1 adds the limitation ”the formulation comprises about 0.01 ng/mL to about 1 mg/mL sodium hyaluronate”. Neither of Young or Bruke et al. teach this limitation. Therefore PHOSITA would not be taught or motivated to have a viral formulation comprises about 0.01 ng/mL to about 1 mg/mL sodium hyaluronate. The amendment is effective to obviate the prior basis of the rejection. The rejection is withdrawn.
New grounds of rejection are set forth as necessitated by Applicant’s amendment.
New Claim Objections
Claim 113 is newly objected to because of the following informalities: claim 113 recites “the formulation is a freeze-dried to form a solid”. The first “a” needs to be deleted. Appropriate correction is required.
New Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 104-105, 109 and 111-112 are newly rejected under 35 U.S.C. 102(a)(2) as being anticipated by Boye et al. (US 2020/0405744 A1, with a priority date of 06/27/2019).
Boye et al. teach compositions of rAAV particles and methods for administrating rAAV particles having enhanced transduction properties (Abstract).
Regarding claim 104, Boye et al. teach methods of delivering a cargo to an eye of a subject. In some embodiments, the method comprises administering to an eye of a subject a rAAV particle. In some embodiments, a rAAV particle comprises (a) a capsid that is admixed with hyaluronic acid (HA) and (b) a cargo (parag 0004). In some embodiments, the capsid is pre-incubated with a buffer that comprises HA. In some embodiments, a buffer comprises HA in a concentration of 0.1 %, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.6%, 0.75%, or 1.0% weight by volume (parag 0004). Boye et al. also teach the effects of HA preincubation and co-administration on transduction of AAV2-mediated mCherry expression (parag 0018), indicate the rAAV particles pre-incubated in the buffer comprising HA and administer the mixture of the rAAV particles and the buffer comprising HA. Boye et al. teach the terms "hyaluronic acid" and "HA" encompass hyaluronic acid, hyaluronan, Healan®, and sodium hyaluronate, without regard to the molecular weight or mass thereof (parag 0037). Boye et al. further teach in some embodiments, described are formulations of one or more viral-based compositions described herein in pharmaceutically acceptable solutions for administration to a cell or an animal. This teaching reads on a liquid formulation (i.e., the mixture of rAAV particle and a buffer comprises HA) comprising a viral vector (a rAAV particle), a buffer and HA (sodium hyaluronate), wherein the sodium hyaluronate has a concentration of 0.1% weight by volume (1 mg/ml) in the formulation, as recited in instant claim. Moreover, Boye et al. also teach in some embodiments, described are buffers for storage of a mixture of rAAV vectors or capsids and HA. In some embodiments, the described buffers comprise HA in a concentration of at least about 0.05%, 0.1 %, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.6%, 0.75%, 1.0%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 15% weight by volume (w/v) and BSS (parag 0146). This teaching also reads on a liquid formulation comprising a viral vector (a rAAV particle), a buffer and HA (sodium hyaluronate), wherein the sodium hyaluronate has a concentration of 0.05% or 0.1% weight by volume (0.5 mg/ml or 1 mg/ml) in the formulation, within the range of 0.01 ng/ml to 1 mg/ml as recited in instant claim.
Regarding claim 105, as discussed above, Boye et al. teach in some embodiments, described are buffers for storage of a mixture of rAAV vectors or capsids and HA. In some embodiments, the described buffers comprise HA in a concentration of at least about 0.05%, 0.1 %, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.6%, 0.75%, 1.0%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 15% weight by volume (w/v) and BSS (parag 0146). This teaching also reads on a liquid formulation comprising a viral vector (a rAAV particle), a buffer and HA (sodium hyaluronate), wherein the sodium hyaluronate has a concentration of 0.05% weight by volume (0.5 mg/ml) in the formulation, within the range of about 0.05 ng/ml to about 0.5 mg/ml, as recited in instant claim.
Regarding claim 109, following the discussion above, Boye et al. further teach in some embodiments, a composition disclosed comprises a pharmaceutically acceptable carrier. In some embodiments, pharmaceutically acceptable carriers include, but are not limited to, buffers such as neutral buffered saline, phosphate buffered saline and the like; carbohydrates such as glucose, mannose, sucrose or dextrans, mannitol (parag 0179).
Regarding claims 111-112, following the discussion above, Boye et al. further teach a buffer for storing a mixture of AAV and hyaluronic acid (HA). In some embodiments, the buff comprises: (a) HA in a concentration of about 0.1%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.6%, 0.75%, 1.0%, 2.0%, 3.0%, 5.0% or 10% weight by volume; (b) balanced salt solution (BSS); (c) artificial cerebrospinal fluid; and/or (d) phosphate buffered saline (PBS). In some embodiments, the buffer further comprises (e) Ringer's lactate solution; (f) TMN200 solution; (g) Polysorbate 20; and/or (h) poloxamer 188 (parag 0011). In some embodiments, the described buffers comprise polysorbate 20 (Tween 20) in a concentration of about at least 0.005%, 0.009%, 0.01 %, 0.014%, 0.02%, 0.1 %, 0.2%, 0.5% or 1 % (parag 0147), wherein the concentration of 0.01 %, 0.014%, 0.02% and 0.1 % is in the range of 0.01% to about 0.1%, and the concentration of 0.2% is in the range of about 0.015% to about 0.025%, as recited in instant claim.
New Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 104-105, 107-109 and 111-112 are newly rejected under 35 U.S.C. 103 as being unpatentable over Boye et al. (US 2020/0405744 A1, with a priority date of 06/27/2019) in view of Wang et al. (Gene Ther. 2017 Jan;24(1):49-59).
Boye et al. teach compositions of rAAV particles and methods for administrating rAAV particles having enhanced transduction properties (Abstract).
Regarding claim 104, Boye et al. teach methods of delivering a cargo to an eye of a subject. In some embodiments, the method comprises administering to an eye of a subject a rAAV particle. In some embodiments, a rAAV particle comprises (a) a capsid that is admixed with hyaluronic acid (HA) and (b) a cargo (parag 0004). In some embodiments, the capsid is pre-incubated with a buffer that comprises HA. In some embodiments, a buffer comprises HA in a concentration of 0.1 %, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.6%, 0.75%, or 1.0% weight by volume (parag 0004). Boye et al. also teach the effects of HA preincubation and co-administration on transduction of AAV2-mediated mCherry expression (parag 0018), indicate the rAAV particles pre-incubated in the buffer comprising HA and administer the mixture of the rAAV particles and the buffer comprising HA. Boye et al. teach the terms "hyaluronic acid" and "HA" encompass hyaluronic acid, hyaluronan, Healan®, and sodium hyaluronate, without regard to the molecular weight or mass thereof (parag 0037). Boye et al. further teach in some embodiments, described are formulations of one or more viral-based compositions described herein in pharmaceutically acceptable solutions for administration to a cell or an animal. This teaching reads on a liquid formulation (i.e., the mixture of rAAV particle and a buffer comprises HA) comprising a viral vector (a rAAV particle), a buffer and HA (sodium hyaluronate), wherein the sodium hyaluronate has a concentration of 0.1% weight by volume (1 mg/ml) in the formulation, as recited in instant claim. Moreover, Boye et al. also teach in some embodiments, described are buffers for storage of a mixture of rAAV vectors or capsids and HA. In some embodiments, the described buffers comprise HA in a concentration of at least about 0.05%, 0.1 %, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.6%, 0.75%, 1.0%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 15% weight by volume (w/v) and BSS (parag 0146). This teaching also reads on a liquid formulation comprising a viral vector (a rAAV particle), a buffer and HA (sodium hyaluronate), wherein the sodium hyaluronate has a concentration of 0.05% or 0.1% weight by volume (0.5 mg/ml or 1 mg/ml) in the formulation, within the range of 0.01 ng/ml to 1 mg/ml as recited in instant claim.
Regarding claim 105, as discussed above, Boye et al. teach in some embodiments, described are buffers for storage of a mixture of rAAV vectors or capsids and HA. In some embodiments, the described buffers comprise HA in a concentration of at least about 0.05%, 0.1 %, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.6%, 0.75%, 1.0%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, or 15% weight by volume (w/v) and BSS (parag 0146). This teaching also reads on a liquid formulation comprising a viral vector (a rAAV particle), a buffer and HA (sodium hyaluronate), wherein the sodium hyaluronate has a concentration of 0.05% weight by volume (0.5 mg/ml) in the formulation, within the range of about 0.05 ng/ml to about 0.5 mg/ml, as recited in instant claim.
Regarding claim 109, following the discussion above, Boye et al. further teach in some embodiments, a composition disclosed comprises a pharmaceutically acceptable carrier. In some embodiments, pharmaceutically acceptable carriers include, but are not limited to, buffers such as neutral buffered saline, phosphate buffered saline and the like; carbohydrates such as glucose, mannose, sucrose or dextrans, mannitol (parag 0179).
Regarding claims 111-112, following the discussion above, Boye et al. further teach a buffer for storing a mixture of AAV and hyaluronic acid (HA). In some embodiments, the buff comprises: (a) HA in a concentration of about 0.1%, 0.2%, 0.25%, 0.3%, 0.35%, 0.4%, 0.45%, 0.5%, 0.6%, 0.75%, 1.0%, 2.0%, 3.0%, 5.0% or 10% weight by volume; (b) balanced salt solution (BSS); (c) artificial cerebrospinal fluid; and/or (d) phosphate buffered saline (PBS). In some embodiments, the buffer further comprises (e) Ringer's lactate solution; (f) TMN200 solution; (g) Polysorbate 20; and/or (h) poloxamer 188 (parag 0011). In some embodiments, the described buffers comprise polysorbate 20 (Tween 20) in a concentration of about at least 0.005%, 0.009%, 0.01 %, 0.014%, 0.02%, 0.1 %, 0.2%, 0.5% or 1 % (parag 0147), wherein the concentration of 0.01 %, 0.014%, 0.02% and 0.1 % is in the range of 0.01% to about 0.1%, and the concentration of 0.2% is in the range of about 0.015% to about 0.025%, as recited in instant claim.
Regarding claims 107 and 108, Boye et al. do not teach the formulation further comprises a globular protein, such as albumin, as well as the concentration of the globular protein. However, this was disclosed by Wang et al. at the time of the instant invention.
Wang et al. identified several proteins from human serum, which directly interact with AAV virions and have the potential to impact AAV transduction (p50, left column).
Regarding claims 107 and 108, Wang et al. teach incubation of all AAV vectors with human serum enhanced AAV transduction, human serum albumin (HSA) directly interacted with the AAV capsid and augmented AAV transduction (see Abstract). Figure 3 (see p53) shows clinical grade human albumin on AAV8 transduction. When 5% clinical grade HSA, which is identical to the serum albumin concentration in the blood of normal subjects, was incubated with AAV vectors at different dilutions, increased AAV transduction was observed in vitro (p50, right column). Herein the 5% HSA diluted in, for instance, 2 or 20 folders (see figure 3A), is within the range of 0.1% to about 5% as recited in instant claim. Wang et al. also teach incubation of HSA with AAV2 or AAV9 induced much higher transduction in vitro and in vivo too (p51, left column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Boye et al.’s formulation comprising rAAV, buffer and sodium hyaluronate, and add human serum albumin as taught by Wang et al.. The skilled artisan would have been motivated to add human serum albumin since Wang et al. teach the human serum albumin (HSA) directly interacted with the AAV capsid and augmented AAV transduction (see Abstract). There would be a reasonable expectation of success of adding albumin in the formulation since Wang et al. teach the concentration of the albumin (i.e., figure 3).
Claims 104-105 and 109 -113 are rejected under 35 U.S.C. 103 as being unpatentable over Boye et al. (US 2020/0405744 A1, with a priority date of 06/27/2019) in view of Fiedler et al. (WO 2018/128689 A1, published in 2018).
The teaching of Boye et al. is set forth above.
Regarding claim 110, Boye et al. do not teach the concentration of sugar (i.e., sucrose) in the formulation. However, it was disclosed by Fiedler et al. at the time of instant invention.
Fiedler et al. teach Adena-associated liquid and lyophilized pharmaceutical compositions (Abstract).
Regarding claim 110, Fiedler et al. teach in exemplary aspects, the pharmaceutical composition of the present disclosure comprises 10 mM to about 150 mM, about 30 mM to about 40 mM, or about 35 mM to about 132 mM sucrose, trehalose, or a combination (parag 0062). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Boye et al.’s formulation comprising rAAV, buffer and sodium hyaluronate, and add sugar (i.e., sucrose) in a concentration of i.e., about 150 mM as taught by Fiedler et al.. The skilled artisan would have been motivated to add sugar (i.e., sucrose) since Fiedler et al. teach sugar and/or sugar alcohol assists in the stability of the liquid and/or lyophilized formulations (parag 0060). There would be a reasonable expectation of success of adding sugar (i.e., sucrose) in the formulation since Fiedler et al. teach the concentration of the sugar (i.e., parag 0062).
Regarding claim 113, Boye et al. do not teach the formulation is freeze-dried to form a solid. However, Fiedler et al. teach in certain embodiments, lyophilization is used to produce a dehydrated
composition, and thus the composition (e.g., the composition that contains the AAV) is a
lyophilized composition (parag 0103).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Boye et al.’s formulation comprising rAAV, buffer and sodium hyaluronate, and freeze- dry the formulation to form a solid as taught by Fiedler et al.. The skilled artisan would have been motivated to freeze-dry (lyophilize) the formulation to form a solid since Fiedler et al. teach a lyophilized composition may facilitate storage of the composition for an extended period of time (e.g., as compared to a liquid formulation of the same composition)(see parag 0029). There would be a reasonable expectation of success of lyophilizing the formulation to form a solid since Fiedler et al. teach the method of lyophilization (i.e., see p79, Example 5).
Conclusion
No claims are 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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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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