DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-20 are currently pending.
Election/Restrictions
Applicant’s election of Group I, Claims 1-13, and of species 500 to 1000 units, and a dynamic viscosity of from 1.5 to 4 Pa*s when determined at 25℃ using an oscillation frequency of 1 Hz, in the reply filed on 2/6/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The requirement is still deemed proper and is therefore made FINAL.
Claims 6, 8 and 10-20 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and species, there being no allowable generic or linking claims.
Claims 1-5, 7 and 9 are being examined in this application, insofar as they read on the elected species of 500 to 1000 units, and a dynamic viscosity of from 1.5 to 4 Pa*s when determined at 25℃ using an oscillation frequency of 1 Hz.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5, 7 and 9 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claim 1 is directed to a composition comprising purified or recombinant botulinum neurotoxin, and non-crosslinked hyaluronic acid, wherein the composition is a sterilized composition, total hyaluronic acid in the composition has an average molecular weight of 2.5 MDa to 4.5 MDa. The claimed purified botulinum neurotoxin is naturally occurring (instant specification, para 0003), and the claimed non-crosslinked hyaluronic acid is naturally occurring. There is no indication in the instant specification that the claimed purified botulinum neurotoxin and the claimed non-crosslinked hyaluronic acid have any characteristics that are different from the naturally occurring botulinum neurotoxin and hyaluronic acid. Claim 1 also recite the composition is a sterilized composition. However, the optimized sterilization condition does not affect the material properties of botulinum neurotoxin and hyaluronic acid. Thus, the claimed purified botulinum neurotoxin and the claimed non-crosslinked hyaluronic acid do not have markedly different characteristics from their natural counterpart in their natural state, and are “product of nature” exception. Accordingly, claim 1 is directed to an exception. Therefore, claim 1 does not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101.
Claim 2 recites the botulinum neurotoxin is botulinum neurotoxin type A. The claimed botulinum neurotoxin type A is naturally occurring (instant specification, para 0023). There is no indication in the instant specification that the claimed botulinum neurotoxin type A has any characteristics that are different from the naturally occurring botulinum neurotoxin type A. Thus, the claimed botulinum neurotoxin type A does not have markedly different characteristics from its natural counterpart in its natural state. Accordingly, claim 2 is directed to an exception. Therefore, claim 2 does not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101.
Claims 3, 5, 7, and 9 recite limitations regarding polydispersity index of the hyaluronic acid, dynamic viscosity of the composition, an amount of the botulinum neurotoxin, and an amount of the hyaluronic acid, respectively. These limitations do not result in botulinum neurotoxin and hyaluronic acid that are different from the naturally occurring botulinum neurotoxin and hyaluronic acid, and do not add significantly more to the exception. Therefore, claims 3, 5, 7, and 9 do not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101.
Claim 4 recites an additional component, wherein the component can be a salt. A salt is naturally occurring. There is no indication in the instant specification that the claimed salt has any characteristics that are different from the naturally occurring salt. Thus, the claimed salt does not have markedly different characteristics from its natural counterpart in its natural state. Accordingly, claim 4 is directed to an exception. Therefore, claim 4 does not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101.
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 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 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2, 4 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Tezel et al (US 2009/0155314 A1; 6/18/2009. Cited on IDS).
The instant claims recite a composition comprising: a) purified or recombinant botulinum neurotoxin; and b) hyaluronic acid, wherein the hyaluronic acid in the composition consists of non- crosslinked hyaluronic acid, said composition is a sterilized composition, and wherein total hyaluronic acid in the composition has an average molecular weight of 2.5 MDa to 4.5 MDa.
Tezel teaches a formulation comprising a hyaluronic acid and a botulinum toxin (Abstract), wherein the botulinum toxin is a botulinum neurotoxin type A as either pure toxin or recombinant botulinum neurotoxin (para 0025, 0039), the hyaluronic acid is a non-cross linked hyaluronic acid, the molecular weight of the hyaluronic acid is between about 10,000 Daltons and about 20 million Daltons (about 0.01 MDa – about 20 MDa) (para 0036), or about 2 million Daltons (about 2 MDa) (para 0065), the botulinum toxin type A, sodium chloride, and sodium hyaluronate (also called hyaluronic acid, para 0008) are sterile (para 0019, 0074). Table 1 demonstrates a formulation comprises 1000 units of botulinum toxin type A, 2.5% w/v of sodium hyaluronate, and sodium chloride (a salt). The viscosity of the composition can be between about 100 cps and about 300,000 cps (about 0.1 Pa*s – about 300 Pa*s) at 25℃ at a shear rate of 0.1/second (dynamic viscosity) (para 0039), or at least about 1000 cps (at least about 1 Pa*s) (para 0059).
Tezel does not teach the formulation wherein total hyaluronic acid in the composition has an average molecular weight of 2.5 MDa to 4.5 MDa (claim 1).
However, Tezel does teach the formulation wherein the molecular weight of the hyaluronic acid is between about 10,000 Daltons and about 20 million Daltons (about 0.01 MDa – about 20 MDa) (which encompasses the claimed range) (para 0036), or about 2 million Daltons (about 2 MDa) (para 0065). Tezel teaches increasing the molecular weight of the hyaluronic acid used in the formulation results in a longer tissue residence time of the formulation and reduce diffusion of the botulinum neurotoxin from the formulation to adjacent muscle groups and importantly also reduces systemic complications from the botulinum neurotoxin (para 0047-0048).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to incorporate hyaluronic acid with a desired molecular weight, since Tezel discloses that a higher molecular weight hyaluronic acid can have a longer tissue residence time and be eliminated from a subdermal site through lower local enzymatic process (para 0047). Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference and routine practice to incorporate hyaluronic acid with a desired molecular weight, with a reasonable expectation for successfully obtaining a formulation.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Tezel et al (US 2009/0155314 A1; 6/18/2009. Cited on IDS) as applied to claims 1-2, 4 and 7 above, further in view of Callegaro et al (US 6,020,484; 2/1/2000.).
Tezel does not teach the formulation wherein the polydispersity index of the non-crosslinked hyaluronic acid is 1.1 to 4.0 (claim 3).
However, Tezel does teach the formulation comprises a non-cross linked hyaluronic acid, wherein the molecular weight of the hyaluronic acid is between about 10,000 Daltons and about 20 million Daltons (about 0.01 MDa – about 20 MDa) (para 0036). Callegaro teaches a hyaluronic acid fraction having an average molecular weight comprised between 5,000 and 300,000 and a polydispersion index lower than 1.7 (Abstract).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to incorporate hyaluronic acid with a polydispersity index of 1.1 to 4.0, since Tezel discloses a formulation comprises a non-cross linked hyaluronic acid with a molecular weight between about 10,000 Daltons and about 20 million Daltons, and Callegaro discloses that hyaluronic acid plays a vital role in many biological processes (col.1 line 26-28), and that hyaluronic acid with a polydispersion index lower than 1.7 can be obtained. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference to incorporate hyaluronic acid with a polydispersity index of 1.1 to 4.0, with a reasonable expectation for successfully obtaining a formulation.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Tezel et al (US 2009/0155314 A1; 6/18/2009. Cited on IDS) as applied to claims 1-2, 4 and 7 above, further in view of Williams et al (International Journal of Biomaterials. 2013;2013:1-8.).
Tezel does not teach the formulation wherein the composition has a dynamic viscosity from 1.5 to 4 Pa*s when determined at 25℃ using an oscillation frequency of 1 Hz (claim 5).
However, Tezel does teach the formulation wherein the viscosity of the composition can be between about 100 cps and about 300,000 cps (about 0.1 Pa*s – about 300 Pa*s, which encompasses the claimed range) at 25℃ at a shear rate of 0.1/second (dynamic viscosity) (para 0039), or at least about 1000 cps (at least about 1 Pa*s) (para 0059). Before the effective filing date of the claimed invention, it was well-known in the art that viscosity is determined using an oscillation frequency of 1 Hz, as evidenced by Williams (p.2 col right – para 3).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to obtain a composition with a desired dynamic viscosity when determined at 25℃ using an oscillation frequency of 1 Hz, since Tezel discloses that the hyaluronic acid is present in an amount effective in providing the desired viscosity to the improved formulation (para 0061), and Williams discloses that viscosity is routinely determined at 25℃ using an oscillation frequency of 1 Hz. Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited reference and routine practice to obtain a composition with a desired dynamic viscosity when determined at 25℃ using an oscillation frequency of 1 Hz with a reasonable expectation of success.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Tezel et al (US 2009/0155314 A1; 6/18/2009. Cited on IDS) as applied to claims 1-2, 4 and 7 above, further in view of Petrella (US 2010/0172940 A1; 7/8/2010. Cited on IDS).
Tezel does not teach the formulation wherein the amount of non-crosslinked hyaluronic acid is at least 0.25 mg (claim 9).
However, Tezel does teach the formulation comprises a non-crosslinked hyaluronic acid, wherein the concentration of hyaluronic acid in the formulation can be between about 0.1 wt% and about 99 wt% (para 0036), or the amount of hyaluronic acid is 2.5% w/v (Table 1). Petrella teaches a composition comprises botulinum toxin and hyaluronic acid (para 0024), wherein the amount of hyaluronic acid is from about 0.1 mg to 5 mg (para 0071).
Thus, before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to optimize the amount of non-crosslinked hyaluronic acid, since Tezel discloses a formulation comprises botulinum toxin and a non-crosslinked hyaluronic acid, wherein increasing the concentration of a hyaluronic acid in the formulation results in a longer tissue residence time of the formulation and reduce diffusion of the botulinum neurotoxin from the formulation to adjacent muscle groups and importantly also reduces systemic complications from the botulinum neurotoxin (para 0048), and Petrella discloses a composition comprises botulinum toxin and hyaluronic acid, wherein the amount of hyaluronic acid is from about 0.1 mg to 5 mg. Generally, differences in concentration will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. (MPEP 2144.05 II) Moreover, before the effective filing date of the claimed invention, one of ordinary skill in the art would have been motivated by the cited references and routine practice to optimize the amount of non-crosslinked hyaluronic acid, with a reasonable expectation for successfully obtaining a formulation.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-5, 7 and 9 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-4, 6 and 10 of U.S. Patent No 11,969,461 B2 (referred to as the ‘461 patent).
Claims 1-4, 6 and 10 of the ‘461 patent recite a composition comprising: a) purified or recombinant botulinum neurotoxin; b) sterilized saline; and c) non-crosslinked hyaluronic acid having an average molecular weight of 2.5 MDa to 4.5 MDa, wherein said composition is a sterilized composition having a dynamic viscosity from 1.5 to 4 Pa*s when determined at 25°C using an oscillation frequency of 1 Hz. The botulinum neurotoxin is botulinum neurotoxin type A. The polydispersity index of the non-crosslinked hyaluronic acid is 1.1 to 4.0. The composition further comprises a salt. The amount of botulinum neurotoxin is 500 to 1000 units. The amount of non-crosslinked hyaluronic acid is at least 0.25 mg.
Conclusion
No claims are allowed.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN Y FAN whose telephone number is (571)270-3541. The examiner can normally be reached on M-F 7am-4pm.
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/Lynn Y Fan/
Primary Examiner, Art Unit 1759