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 .
Election/Restrictions
Applicant’s election without traverse of invention I in the reply filed on 6/12/26 is acknowledged.
Claims 76, 90 and 91 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/12/26.
Claims 1-2, 8, 10, 20, 23, 25, 52, 60-61, 67-75, 88 and 89 are examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/20/24 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 2, 8 and 10 are objected to because of the following informalities: each claim contains more than one "period". Appropriate correction is required.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 8, 10, 60, 61, 69 and 74 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “about” in claim 2, 8, 10, 60, 61 and 74 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what the metes and bounds of “about” are relative to the claim limitations of claims 2, 8, 10, 60, 61 and 74.
Claim 8 recites, “less than about or about 0.1 Pa, less than about or about 0.01Pa, less than about or about 0.001 Pa or zero…” The recitation of “less than about” is unclear since the metes and bounds of what constitutes this limitation are not defined by the claim or the specification. Additionally, the recitation of “less than about” would include values greater than 0.1 Pa for example, thereby contradicting “less than”.
The term “smaller” in claim 10, part b. is a relative term which renders the claim indefinite. The term “smaller” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is therefore unclear what the metes and bounds of a smaller circumferential spread are in view of the claim as written and in view of the specification as filed.
Claim 10, part c. recites, “the thickness at a site of injection after suprachoroidal administration of the pharmaceutical composition is equal to or higher than the thickness at a site of injection…”. However, it is unclear what the claim is referring to with regard to a thickness at a site of injection.
Claim 60 recites the limitation "the vector genome concentration" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 69 recites, “The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises 0-16% (weight/volume) poloxamer 188.” However, if the composition comprises 0% of poloxamer 188, then it is unclear if poloxamer 188 is part of the composition.
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.
Claim 69 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. Claim 69 recites, “The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises 0-16% (weight/volume) poloxamer 188.” However, if the composition comprises 0% of poloxamer 188, then claim 69 does not further limit claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 52 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of diseases is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: different diseases that impact the eye.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 2, 8, 10, 23, 52, 60, 61, 69 and 88 are rejected under 35 U.S.C. 102a1 as being anticipated by Yiu et al. (Molecular Therapy, 2020, Vol. 16).
MPEP 2112 I. and II. establish that something which is old does not become patentable upon the discovery of a new property and inherent feature need not be recognized at the relevant time, respectively.
The claimed invention is drawn to a pharmaceutical composition suitable for administration to the suprachoroidal space (SCS) of an eye of a human subject, wherein the pharmaceutical composition comprises a recombinant adeno-associated virus 8 (AAV8) vector comprising an expression cassette encoding a transgene, and wherein the pharmaceutical has a viscosity and/or higher elastic modulus that increases with increasing temperature.
The composition has a viscosity of less than, or about, 183 mPas at 20-Celsius as measured at a shear rate of at about 1/s to 1000/s; the elastic modulus of the pharmaceutical composition at under 27-Celsius is less than about 0.1Pa; the clearance time of the pharmaceutical composition after suprachoroidal administration is equal to or greater than the clearance time of a reference pharmaceutical composition after suprachoroidal administration, wherein the reference pharmaceutical composition comprises the recombinant AAV comprising the expression cassette encoding the transgene, wherein an amount of the recombinant AAV genome copies is the same when the pharmaceutical composition or the reference pharmaceutical composition is administered to the suprachoroidal space, and wherein the reference pharmaceutical composition has a lower viscosity and/or lower elastic modulus than the pharmaceutical composition at about 32-35°C;
The vector genome concentration of the recombinant AAV vector is about 6.2 x 10^11 GC/mL and the total number of genome copies is about 6 x 10^11.
The pharmaceutical composition comprises 0% (weight/volume) of poloxamer 188.
The claimed invention structurally requires a recombinant AAV vector comprising an expression cassette encoding a transgene. No additional component is part of the claimed pharmaceutical composition. Therefore, if the prior art teaches a recombinant AAV 8 vector with a transgene and at a genome concentration of about 6.2 x 10^11 GC/mL and the total number of genome copies is about 6 x 10^11, then the prior art teaches the claimed invention in view of the guidance from MPEP 2112 summarized above.
Furthermore the claimed intended use of “for administration to the suprachoroidal space of an eye of a human subject”, and the subject has nAMD in view as an intended use limitation (MPEP 2111.02) and therefore does not impart patentability to claimed product.
The Prior Art
Yiu et al. teach the delivery of recombinant AAV8 encoding the transgene for enhanced green fluorescent protein into the suprachoroidal space of the eye of a primate at a dosage of 7x10^11 or 7x10^12 vector genomes/eye. [see page 180, first paragraph of right column] In view of the “about” limitations for the genome concentration and genome copies, Yiu et al. teach a pharmaceutical composition comprising a recombinant AAV8 at these amounts of genome. Furthermore, in view of the guidance from MPEP 2112 summarized above, the pharmaceutical composition of Yiu et al. inherently possesses the claimed properties required by claims 2, 8 and 10. Therefore, Yiu et al. anticipate the claimed invention.
Claim(s) 1, 2, 8, 10, 20, 23, 60, 61, 69 and 88 are rejected under 35 U.S.C. 102a1 as being anticipated by Simpson et al. (US PGPub 2019/0127455).
MPEP 2112 I. and II. establish that something which is old does not become patentable upon the discovery of a new property and inherent feature need not be recognized at the relevant time, respectively.
The claimed invention is drawn to a pharmaceutical composition suitable for administration to the suprachoroidal space (SCS) of an eye of a human subject, wherein the pharmaceutical composition comprises a recombinant adeno-associated virus 8 (AAV8) vector comprising an expression cassette encoding a transgene, and wherein the pharmaceutical has a viscosity and/or higher elastic modulus that increases with increasing temperature.
The composition has a viscosity of less than, or about, 183 mPas at 20-Celsius as measured at a shear rate of at about 1/s to 1000/s; the elastic modulus of the pharmaceutical composition at under 27-Celsius is less than about 0.1Pa; the clearance time of the pharmaceutical composition after suprachoroidal administration is equal to or greater than the clearance time of a reference pharmaceutical composition after suprachoroidal administration, wherein the reference pharmaceutical composition comprises the recombinant AAV comprising the expression cassette encoding the transgene, wherein an amount of the recombinant AAV genome copies is the same when the pharmaceutical composition or the reference pharmaceutical composition is administered to the suprachoroidal space, and wherein the reference pharmaceutical composition has a lower viscosity and/or lower elastic modulus than the pharmaceutical composition at about 32-35°C;
The vector genome concentration of the recombinant AAV vector is about 6.2 x 10^11 GC/mL and the total number of genome copies is about 6 x 10^11.
The pharmaceutical composition comprises 0% (weight/volume) of poloxamer 188.
The recombinant AAV comprises an expression cassette comprising:
(1) control elements comprising a) a CB7 promoter, comprising a CMV enhancer/chicken ß-actin promoter, b) a chicken ß-actin intron and c) a rabbit ß- globin poly A signal; and
(2) nucleic acid sequences encoding heavy and light chains of the anti-VEGF Fab, separated by a self-cleaving furin (F)/F2A linker, wherein the anti-VEGF Fab comprises: (A) light chain CDRs 1-3 of SEQ ID NOs: 14-16 and heavy chain CDRs 1-3 of SEQ ID NOs: 20, 18, and 21; or (B) a heavy chain comprising the amino acid sequence of SEQ ID NO:2, and a light chain comprising the amino acid sequence of SEQ ID NO:1, wherein AAV2 inverted terminal repeats flank the expression cassette.
The claimed invention structurally requires a recombinant AAV vector comprising an expression cassette encoding a transgene. No additional component is part of the claimed pharmaceutical composition. Therefore, if the prior art teaches a recombinant AAV 8 vector with a transgene and at a genome concentration of about 6.2 x 10^11 GC/mL and the total number of genome copies is about 6 x 10^11, then the prior art teaches the claimed invention in view of the guidance from MPEP 2112 summarized above.
Furthermore the claimed intended use of “for administration to the suprachoroidal space of an eye of a human subject”, and the subject has nAMD in view as an intended use limitation (MPEP 2111.02) and therefore does not impart patentability to claimed product.
The Prior Art
Simpson et al. teach at paragraphs 270 and 271: “The vector used in this study (referred to herein as “Vector 1”) is a non-replicating AAV8 vector containing a gene cassette encoding a humanized mAb antigen-binding fragment that binds and inhibits human VEGF, flanked by AAV2 inverted terminal repeats (ITRs). Expression of heavy and light chains in Vector 1 is controlled by the CB7 promoter consisting of the chicken β-actin promoter and CMV enhancer, and the vector also comprises a chicken β-actin intron, and a rabbit β-globin polyA signal. In Vector 1, the nucleic acid sequences coding for the heavy and light chains of anti-VEGF Fab are separated by a self-cleaving furin (F)/F2A linker. Rho/VEGF mice were injected subretinally with either Vector 1 or control (n=10-17 per group) and one week later the amount of retinal neovascularization was quantitated.
[0271] The total area of retinal neovascularization was significantly reduced (p<0.05) in Rho/VEGF mice receiving Vector 1 in a dose-dependent manner, as compared to mice receiving either phosphate buffered saline (PBS) or null AAV8 vector. The effectiveness criterion was set as a statistically significant reduction in the area of retinal neovascularization. With this criterion, a minimum dose of 1×10.sup.7 GC/eye of Vector 1 was determined to be efficacious for reduction of retinal neovascularization in the murine transgenic Rho/VEGF model for nAMD in human subjects (FIG. 4).:” A specific example of an anti-VEGF antibody or Fab is that is SEQ ID NO:s 1 and 2, which are identical to SEQ ID NO:s 1 and 2, therefore also comprise the CDRs of SEQ ID NO:s 14-16, 20, 18 and 21.
In view of the “about” limitations for the genome concentration and genome copies, Simpson et al. teach a pharmaceutical composition comprising a recombinant AAV8 at these amounts of genome. Furthermore, in view of the guidance from MPEP 2112 summarized above, the pharmaceutical composition of Simpson et al. inherently possesses the claimed properties required by claims 2, 8 and 10. Therefore, Simpson et al. anticipate the claimed invention.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 25, 67, 68, 70-75 and 89 are rejected under 35 U.S.C. 103 as being unpatentable over Simpson et al. as applied to claims 1, 2, 8, 10, 20, 23, 60, 61, 69 and 88 above, and further in view of Bunting et al. (US PGPub 2017/0087219) and Kotin et al. (US PGPub 2017/0130245).
The pharmaceutical composition also comprises:
sucrose; or
poloxamer 407 and poloxamer 188 (also known as pluronic F68); or
modified Dulbecco’s PBS and sucrose; or
about 2.70 mmol/L potassium chloride, about 1.47 mmol/L potassium phosphate monobasic, about 100 mmol/L sodium chloride, about 8.10 mmol/L sodium phosphate dibasic, and about 117 mmol/L sucrose; or
potassium chloride, potassium phosphate monobasic, sodium chloride, sodium phosphate dibasic, and sucrose.
The amount of poloxamer 407 is 16-22% (weight/volume) or poloxamer 407 is 19% (weight/volume) poloxamer 407 and 6% (weight/volume) poloxamer 188 or poloxamer 407 is 18% (weight/volume) poloxamer 407 and 6.5% (weight/volume) poloxamer 188 or poloxamer 407 is 17.5% (weight/volume) poloxamer 407 and 7% (weight/volume) poloxamer 188.
The teachings of Simpson et al. are summarized above, however, they do not teach adding sucrose, poloxamers, or potassium chloride, potassium phosphate monobasic, sodium chloride, and sodium phosphate dibasic as presently claimed.
Bunting et al. teach formulating recaombinant AAV with Dulbecco’s PBS and 0.001% Poloxamer 188. [see paragraph 246] Bunting et al. also teach at paragraph 177 “[0177] In certain aspects, the formulation comprising recombinant AAV FVIII virions further comprises one or more buffering agents. For example, in various aspects, the formulation of the present invention comprises sodium phosphate dibasic at a concentration of about 0.1 mg/ml to about 3 mg/ml, about 0.5 mg/ml to about 2.5 mg/ml, about 1 mg/ml to about 2 mg/ml, or about 1.4 mg/ml to about 1.6 mg/ml. In a particularly preferred embodiment, the AAV FVIII formulation of the present invention comprises about 1.42 mg/ml of sodium phosphate, dibasic (dried). Another buffering agent that may find use in the recombinant AAV FVIII formulations of the present invention is sodium phosphate, monobasic monohydrate which, in some embodiments, finds use at a concentration of from about 0.1 mg/ml to about 3 mg/ml, about 0.5 mg/ml to about 2.5 mg/ml, about 1 mg/ml to about 2 mg/ml, or about 1.3 mg/ml to about 1.5 mg/ml. In a particularly preferred embodiment, the AAV FVIII formulation of the present invention comprises about 1.38 mg/ml of sodium phosphate, monobasic monohydrate. In a yet more particularly preferred embodiment of the present invention, the recombinant AAV FVIII formulation of the present invention comprises about 1.42 mg/ml of sodium phosphate, dibasic and about 1.38 mg/ml of sodium phosphate, monobasic monohydrate.”
At paragraphs 180 and 181, “In yet another aspect, the recombinant AAV FVIII formulations of the present invention may comprise one or more surfactants, which may be non-ionic surfactants. Exemplary surfactants include ionic surfactants, non-ionic surfactants, and combinations thereof. For example, the surfactant can be, without limitation, TWEEN 80 (also known as polysorbate 80, or its chemical name polyoxyethylene sorbitan monooleate), sodium dodecylsulfate, sodium stearate, ammonium lauryl sulfate, TRITON AG 98 (Rhone-Poulenc), poloxamer 407, poloxamer 188 and the like, and combinations thereof. In a particularly preferred embodiment, the formulation of the present invention comprises poloxamer 188, which may be present at a concentration of from about 0.1 mg/ml to about 4 mg/ml, or from about 0.5 mg/ml to about 3 mg/ml, from about 1 mg/ml to about 3 mg/ml, about 1.5 mg/ml to about 2.5 mg/ml, or from about 1.8 mg/ml to about 2.2 mg/ml. In a particularly preferred embodiment, poloxamer 188 is present at a concentration of about 2.0 mg/ml.
In a particular preferred embodiment of the present invention, the pharmaceutical formulation of the present invention comprises AAV5-FVIII-SQ formulated in a liquid solution that comprises about 1.42 mg/ml of sodium phosphate, dibasic, about 1.38 mg/ml of sodium phosphate, monobasic monohydrate, about 8.18 mg/ml sodium chloride, about 20 mg/ml mannitol and about 2 mg/ml poloxamer 188.”
Bunting et al. also teach the use of sucrose or mannitol as a bulking agent for AAV formulations [see paragraph 179].
Kotin et al. teach producing AAV, including AAV8 and the formulation of different buffers, such as lysing buffers and stabilizing buffers. [see paragraphs 30, 38, 408 and 394-395] Kotin et al. also teach that buffering agents can be based on combinations of exemplary buffering agents may also include, but are not limited to, citrate buffer solutions, acetate buffer solutions, phosphate buffer solutions, ammonium chloride, calcium carbonate, calcium chloride, calcium citrate, calcium glubionate, calcium gluceptate, calcium gluconate, D-gluconic acid, calcium glycerophosphate, calcium lactate, propanoic acid, calcium levulinate, pentanoic acid, dibasic calcium phosphate, phosphoric acid, tribasic calcium phosphate, calcium hydroxide phosphate, potassium acetate, potassium chloride, potassium gluconate, potassium mixtures, dibasic potassium phosphate, monobasic potassium phosphate, potassium phosphate mixtures, sodium acetate, sodium bicarbonate, sodium chloride, sodium citrate, sodium lactate, dibasic sodium phosphate, monobasic sodium phosphate, sodium phosphate.
It would have been obvious to one of ordinary skill in the art to modify the compositions taught by Simpson et al. in order to formulate the claimed recombinant AAV with:
sucrose; or
modified Dulbecco’s PBS and sucrose; or
about 2.70 mmol/L potassium chloride, about 1.47 mmol/L potassium phosphate monobasic, about 100 mmol/L sodium chloride, about 8.10 mmol/L sodium phosphate dibasic, and about 117 mmol/L sucrose; or
potassium chloride, potassium phosphate monobasic, sodium chloride, sodium phosphate dibasic, and sucrose; or
poloxamer 407 and poloxamer 188 (also known as pluronic F68); wherein the amount of poloxamer 407 is 16-22% (weight/volume) or poloxamer 407 is 19% (weight/volume) poloxamer 407 and 6% (weight/volume) poloxamer 188 or poloxamer 407 is 18% (weight/volume) poloxamer 407 and 6.5% (weight/volume) poloxamer 188 or poloxamer 407 is 17.5% (weight/volume) poloxamer 407 and 7% (weight/volume) poloxamer 188.
One would have been motivated to do so, given the suggestion by Simpson et al. that the pharmaceutical compositions containing recombinant AAV can be formulated to include buffers, surfactants and excipients. There would have been a reasonable expectation of success, given the knowledge that AAV can be formulated with Dulbecco’s PBS and 0.001% Poloxamer 188; or sodium phosphate and monobasic monohydrate; or the recombinant AAV FVIII formulations of may comprise one or more surfactants, which may be non-ionic surfactants. Exemplary surfactants include ionic surfactants, non-ionic surfactants, and combinations thereof. For example, the surfactant can be, poloxamer 407, poloxamer 188 and the like, and combinations thereof; or sucrose or mannitol, as taught by Bunting et al., and also given the knowledge that buffering agents containing as potassium chloride, potassium phosphate monobasic, sodium chloride or sodium phosphate dibasic, can be used in formulating viruses, such as AAV, as taught by Kotin et al. Furthermore, MPEP § 2144.05 (II) (A) states, “…Optimization Within Prior Art Conditions or Through Routine Experimentation…“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to dis-cover the optimum or workable ranges by routine experimentation…”. Therefore, based on the combined teachings of Simpson et al., Bunting et al. and Kotin et al., and through routine optimization, the claimed percentages of poloxamer 407, poloxamer 188, concentrations of potassium chloride, potassium phosphate, sodium chloride and sodium phosphate and use of sucrose or Dulbecco’s PBS of the instant invention would be readily apparent to one of ordinary skill in the art. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 8, 10, 20, 23, 25, 52, 60-61, 67-75, 88 and 89 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 8, 10, 20. 24, 26, 61, 69, 70, 76, 82, 83, 84, 98 and 100 of copending Application No. 18854403 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the invention of the copending application and the instant invention are both drawn to a pharmaceutical composition suitable for administration to the suprachoroidal space (SCS) of an eye, wherein the pharmaceutical composition comprises a recombinant adeno-associated virus 8 (AAV8) vector comprising an expression cassette encoding a transgene, and wherein the pharmaceutical has a viscosity and/or higher elastic modulus that increases with increasing temperature.
The recombinant AAV comprises an expression cassette comprising:
(1) control elements comprising a) a CB7 promoter, comprising a CMV enhancer/chicken ß-actin promoter, b) a chicken ß-actin intron and c) a rabbit ß- globin poly A signal; and
(2) nucleic acid sequences encoding heavy and light chains of the anti-VEGF Fab, separated by a self-cleaving furin (F)/F2A linker, wherein the anti-VEGF Fab comprises: (A) light chain CDRs 1-3 of SEQ ID NOs: 14-16 and heavy chain CDRs 1-3 of SEQ ID NOs: 20, 18, and 21; or (B) a heavy chain comprising the amino acid sequence of SEQ ID NO:2, and a light chain comprising the amino acid sequence of SEQ ID NO:1, wherein AAV2 inverted terminal repeats flank the expression cassette.
The composition has a viscosity of less than, or about, 183 mPas at 20-Celsius as measured at a shear rate of at about 1/s to 1000/s; the elastic modulus of the pharmaceutical composition at under 27-Celsius is less than about 0.1Pa; the clearance time of the pharmaceutical composition after suprachoroidal administration is equal to or greater than the clearance time of a reference pharmaceutical composition after suprachoroidal administration, wherein the reference pharmaceutical composition comprises the recombinant AAV comprising the expression cassette encoding the transgene, wherein an amount of the recombinant AAV genome copies is the same when the pharmaceutical composition or the reference pharmaceutical composition is administered to the suprachoroidal space, and wherein the reference pharmaceutical composition has a lower viscosity and/or lower elastic modulus than the pharmaceutical composition at about 32-35°C;
The vector genome concentration of the recombinant AAV vector is about 6.2 x 10^11 GC/mL and the total number of genome copies is about 6 x 10^11.
The pharmaceutical composition comprises 0% (weight/volume) of poloxamer 188.
The pharmaceutical composition also comprises:
sucrose; or
poloxamer 407 and poloxamer 188 (also known as pluronic F68); or
modified Dulbecco’s PBS and sucrose; or
about 2.70 mmol/L potassium chloride, about 1.47 mmol/L potassium phosphate monobasic, about 100 mmol/L sodium chloride, about 8.10 mmol/L sodium phosphate dibasic, and about 117 mmol/L sucrose; or
potassium chloride, potassium phosphate monobasic, sodium chloride, sodium phosphate dibasic, and sucrose.
The amount of poloxamer 407 is 16-22% (weight/volume) or poloxamer 407 is 19% (weight/volume) poloxamer 407 and 6% (weight/volume) poloxamer 188 or poloxamer 407 is 18% (weight/volume) poloxamer 407 and 6.5% (weight/volume) poloxamer 188 or poloxamer 407 is 17.5% (weight/volume) poloxamer 407 and 7% (weight/volume) poloxamer 188.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8, 10, 23, 25, 52, 60-61, 67, 73-75 and 88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 13, 15, 18, 20, 21, 48, 56, 57, 63, 80, 81-84, 86, of copending Application No. 18030630 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the invention of the copending application and the instant invention are both drawn to a pharmaceutical composition suitable for administration to the suprachoroidal space (SCS) of an eye, wherein the pharmaceutical composition comprises a recombinant adeno-associated virus 8 (AAV8) vector comprising an expression cassette encoding a transgene, and wherein the pharmaceutical has a viscosity and/or higher elastic modulus that increases with increasing temperature.
The composition has a viscosity of less than, or about, 183 mPas at 20-Celsius as measured at a shear rate of at about 1/s to 1000/s; the elastic modulus of the pharmaceutical composition at under 27-Celsius is less than about 0.1Pa; the clearance time of the pharmaceutical composition after suprachoroidal administration is equal to or greater than the clearance time of a reference pharmaceutical composition after suprachoroidal administration, wherein the reference pharmaceutical composition comprises the recombinant AAV comprising the expression cassette encoding the transgene, wherein an amount of the recombinant AAV genome copies is the same when the pharmaceutical composition or the reference pharmaceutical composition is administered to the suprachoroidal space, and wherein the reference pharmaceutical composition has a lower viscosity and/or lower elastic modulus than the pharmaceutical composition at about 32-35°C;
The vector genome concentration of the recombinant AAV vector is about 6.2 x 10^11 GC/mL and the total number of genome copies is about 6 x 10^11.
The pharmaceutical composition also comprises:
sucrose; or
poloxamer 407 and poloxamer 188 (also known as pluronic F68); or
modified Dulbecco’s PBS and sucrose; or
about 2.70 mmol/L potassium chloride, about 1.47 mmol/L potassium phosphate monobasic, about 100 mmol/L sodium chloride, about 8.10 mmol/L sodium phosphate dibasic, and about 117 mmol/L sucrose; or
potassium chloride, potassium phosphate monobasic, sodium chloride, sodium phosphate dibasic, and sucrose.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8, 10, 20, 23, 25, 52, 60-61, 67, 73-75 and 88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 9, 10, 54, 55, 57, 67, 190, 195, 196, 200, 201, 202, 213, 214 of copending Application No. 17766941 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the invention of the copending application and the instant invention are both drawn to a pharmaceutical composition suitable for administration to the suprachoroidal space (SCS) of an eye, wherein the pharmaceutical composition comprises a recombinant adeno-associated virus 8 (AAV8) vector comprising an expression cassette encoding a transgene, and wherein the pharmaceutical has a viscosity and/or higher elastic modulus that increases with increasing temperature.
The recombinant AAV comprises an expression cassette comprising:
(1) control elements comprising a) a CB7 promoter, comprising a CMV enhancer/chicken ß-actin promoter, b) a chicken ß-actin intron and c) a rabbit ß- globin poly A signal; and
(2) nucleic acid sequences encoding heavy and light chains of the anti-VEGF Fab, separated by a self-cleaving furin (F)/F2A linker, wherein the anti-VEGF Fab comprises: (A) light chain CDRs 1-3 of SEQ ID NOs: 14-16 and heavy chain CDRs 1-3 of SEQ ID NOs: 20, 18, and 21; or (B) a heavy chain comprising the amino acid sequence of SEQ ID NO:2, and a light chain comprising the amino acid sequence of SEQ ID NO:1, wherein AAV2 inverted terminal repeats flank the expression cassette.
The composition has a viscosity of less than, or about, 183 mPas at 20-Celsius as measured at a shear rate of at about 1/s to 1000/s; the elastic modulus of the pharmaceutical composition at under 27-Celsius is less than about 0.1Pa; the clearance time of the pharmaceutical composition after suprachoroidal administration is equal to or greater than the clearance time of a reference pharmaceutical composition after suprachoroidal administration, wherein the reference pharmaceutical composition comprises the recombinant AAV comprising the expression cassette encoding the transgene, wherein an amount of the recombinant AAV genome copies is the same when the pharmaceutical composition or the reference pharmaceutical composition is administered to the suprachoroidal space, and wherein the reference pharmaceutical composition has a lower viscosity and/or lower elastic modulus than the pharmaceutical composition at about 32-35°C;
The vector genome concentration of the recombinant AAV vector is about 6.2 x 10^11 GC/mL and the total number of genome copies is about 6 x 10^11.
The pharmaceutical composition comprises 0% (weight/volume) of poloxamer 188.
The pharmaceutical composition also comprises:
sucrose; or
poloxamer 407 and poloxamer 188 (also known as pluronic F68); or
modified Dulbecco’s PBS and sucrose; or
about 2.70 mmol/L potassium chloride, about 1.47 mmol/L potassium phosphate monobasic, about 100 mmol/L sodium chloride, about 8.10 mmol/L sodium phosphate dibasic, and about 117 mmol/L sucrose; or
potassium chloride, potassium phosphate monobasic, sodium chloride, sodium phosphate dibasic, and sucrose.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14 and 15 of copending Application No. 17912248 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the invention of the copending application and the instant invention are both drawn to a pharmaceutical composition suitable for administration to the suprachoroidal space (SCS) of an eye, wherein the pharmaceutical composition comprises a recombinant adeno-associated virus 8 (AAV8) vector comprising an expression cassette encoding a transgene.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 8, 10, 23, 25, 52, 60-61, 67, 73-75 and 88 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 15, 48, 56, 57, 92 and 94 of copending Application No. 18030621 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the invention of the copending application and the instant invention are both drawn to a pharmaceutical composition suitable for administration to the suprachoroidal space (SCS) of an eye, wherein the pharmaceutical composition comprises a recombinant adeno-associated virus 8 (AAV8) vector comprising an expression cassette encoding a transgene, and wherein the pharmaceutical has a viscosity and/or higher elastic modulus that increases with increasing temperature.
The composition has a viscosity of less than, or about, 183 mPas at 20-Celsius as measured at a shear rate of at about 1/s to 1000/s; the elastic modulus of the pharmaceutical composition at under 27-Celsius is less than about 0.1Pa; the clearance time of the pharmaceutical composition after suprachoroidal administration is equal to or greater than the clearance time of a reference pharmaceutical composition after suprachoroidal administration, wherein the reference pharmaceutical composition comprises the recombinant AAV comprising the expression cassette encoding the transgene, wherein an amount of the recombinant AAV genome copies is the same when the pharmaceutical composition or the reference pharmaceutical composition is administered to the suprachoroidal space, and wherein the reference pharmaceutical composition has a lower viscosity and/or lower elastic modulus than the pharmaceutical composition at about 32-35°C;
The vector genome concentration of the recombinant AAV vector is about 6.2 x 10^11 GC/mL and the total number of genome copies is about 6 x 10^11.
The pharmaceutical composition comprises 0% (weight/volume) of poloxamer 188.
The pharmaceutical composition also comprises:
sucrose; or
poloxamer 407 and poloxamer 188 (also known as pluronic F68); or
modified Dulbecco’s PBS and sucrose; or
about 2.70 mmol/L potassium chloride, about 1.47 mmol/L potassium phosphate monobasic, about 100 mmol/L sodium chloride, about 8.10 mmol/L sodium phosphate dibasic, and about 117 mmol/L sucrose; or
potassium chloride, potassium phosphate monobasic, sodium chloride, sodium phosphate dibasic, and sucrose.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 23 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 15 of copending Application No. 19790561 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the invention of the copending application and the instant invention are both drawn to a pharmaceutical composition and a method using the composition suitable for administration to the suprachoroidal space (SCS) of an eye, wherein the pharmaceutical composition comprises a recombinant adeno-associated virus 8 (AAV8) vector comprising an expression cassette encoding a transgene.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 185, 186, 191, 193 and 194 of copending Application No. 19675317 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the invention of the copending application and the instant invention are both drawn to a pharmaceutical composition suitable for administration to the suprachoroidal space (SCS) of an eye, wherein the pharmaceutical composition comprises a recombinant adeno-associated virus 8 (AAV8) vector comprising an expression cassette encoding a transgene.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 20, 23, 25 and 60 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 185, 186, 187, 188, 189, 192, 198, of copending Application No. 19675302 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the invention of the copending application and the instant invention are both drawn to a pharmaceutical composition suitable for administration to the suprachoroidal space (SCS) of an eye, wherein the pharmaceutical composition comprises a recombinant adeno-associated virus 8 (AAV8) vector comprising an expression cassette encoding a transgene, and wherein the pharmaceutical has a viscosity and/or higher elastic modulus that increases with increasing temperature and the inclusion of sucrose or potassium chloride, potassium phosphate monobasic, sodium chloride, sodium phosphate dibasic, and sucrose.
The recombinant AAV comprises an expression cassette comprising:
(1) control elements comprising a) a CB7 promoter, comprising a CMV enhancer/chicken ß-actin promoter, b) a chicken ß-actin intron and c) a rabbit ß- globin poly A signal; and
(2) nucleic acid sequences encoding heavy and light chains of the anti-VEGF Fab, separated by a self-cleaving furin (F)/F2A linker, wherein the anti-VEGF Fab comprises: (A) light chain CDRs 1-3 of SEQ ID NOs: 14-16 and heavy chain CDRs 1-3 of SEQ ID NOs: 20, 18, and 21; or (B) a heavy chain comprising the amino acid sequence of SEQ ID NO:2, and a light chain comprising the amino acid sequence of SEQ ID NO:1, wherein AAV2 inverted terminal repeats flank the expression cassette.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/BENJAMIN P BLUMEL/ Primary Examiner, Art Unit 1671
