DETAILED ACTION
This office action is in response to applicant’s filing dated December 15, 2025.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Notice of Change of Examiner
Please note that the Examiner prosecuting this application has been changed to Examiner Elena Vishnyakova of Art Unit 1691. Please address all future correspondences to Examiner Vishnyakova.
Status of Claims
Claims 9, 11 – 19 and 22 – 30 are pending in the instant application. Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on December 15, 2025 are acknowledged. Claims 22 - 26 remain withdrawn, as being drawn to an unelected invention or specie. Acknowledgement is made of Applicant's amendment of claim 9; cancelation of claims 10 and 20 and addition of new claims 29 and 30.
Claims 9, 11 – 19 and 27 – 30 are under consideration in the instant office action.
Objections and/or Rejections and Response to Arguments
Applicants' arguments, filed on December 15, 2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Modified Objections and/or Rejections
Modifications Necessitated by Claim Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 9, 11-19 and 28 - 30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant’s amendment with respect to claim 9 has been fully considered but is deemed to insert new matter into the claims since the specification as originally filed does not provide support for the limitation, “wherein biodegradable drug delivery composition is insoluble in an aqueous environment”. The only support provide for this recitation is in Example 9 (see US"20120172454", instant Application); Example 9 teaches that the formulation “Upon injection, the solvent diffused away from the formulation and the remaining polymer formed a solid biodegradable implant within the aqueous environment”. This formulation contains specific triblock and diblock copolymers with specific polyester polylactic acid. Instant claim 9 recites broadly any polyester and elected species is poly(lactic-co-glycolic) acid (PLGA) as the polyester A block. There is no support in the specification for “wherein biodegradable drug delivery composition is insoluble in an aqueous environment” when the A block is poly(lactic-co-glycolic acid) (PLGA) polyester.
Any claim containing limitation which does not have basis in the original disclosure should be rejected under 35 U.S.C. 112, first paragraph as failing to comply with the written description requirement. See MPEP § 2163- § 2163.07(b) for a discussion of the written description requirement of 35 U.S.C. 112, first paragraph.
Response to Arguments
Applicant argues:
- Applicant disagrees, that the feature “the biodegradable drug delivery composition is insoluble in an aqueous environment” is not supported by the specification for a composition when the A block is a PLGA polyester. A review of the specification provides support for the invention as claimed, including that the biodegradable drug delivery composition is insoluble in an aqueous environment when the A block is a PLGA polyester. The specification teaches as a general property of the biodegradable drug delivery that the biodegradable drug delivery composition of the invention may be in the form of an injectable liquid that forms a hardened implant on injection, i.e. is insoluble in the aqueous environment of the body. See for example pages: 8 lines 11 – 13; page 17, lines 25 – 29; page 25, lines 19 – 22.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive because: as set forth above, the specification as originally filed does not provide support for the limitation, “wherein biodegradable drug delivery composition is insoluble in an aqueous environment” which indicates an addition of a new matter into the claims. Instant claim 9 recites broadly any polyester and an elected species is poly(lactic-co-glycolic) acid (PLGA) as the polyester A block. There is no support in the specification for “wherein biodegradable drug delivery composition is insoluble in an aqueous environment” when the A block is poly(lactic-co-glycolic acid) (PLGA) polyester. The recitations of pages 8, 17 and 25, pointed out by Applicant as examples, supporting the composition’s feature “wherein biodegradable drug delivery composition is insoluble in an aqueous environment” are not persuasive, because those embodiments recite: “[…]the biodegradable drug delivery composition is an injectable liquid that when it is inserted into the body of an animal or plant becomes a hardened implant."; or “The term "implant" means that the drug delivery compositions are injectable, are in situ forming and are biodegradable and turn into solid implants when injected into the body."
The statement: “the composition […] turns into solid implants when injected into the body” describes an outcome rather than physical/chemical property (aqueous solubility) of the composition, and may not be a result of contact of the composition with water, but due to other factors, e.g. temperature-dependent phase transition or enzymatic actions.
Therefore, applicant’s arguments are not persuasive and the rejection of claims 9, 11-19 and 28 - 30 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is maintained.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
1)Claims 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 27 and 29 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Shih et al. (US 7,649,023, PTO-892 of record in the Parent Application).
Shih et al. discloses drug delivery liquid compositions comprising one or more biodegradable block copolymers as drug carriers comprising AB, ABA or BAB type copolymers; wherein the A block is a biodegradable polyester or poly( ortho ester) and the B block is polyethylene glycol (PEG), and 2) a liquid polyethylene glycol (PEG), a PEG derivative, or a mixtures of PEG and a PEG derivative; wherein the biodegradable block copolymer is insoluble in an aqueous solution but soluble in the PEG and/or PEG derivatives. The composition further includes a drug. The composition can be administered as is. After the administration, the liquid composition forms a drug containing depot and slowly releases the active substance over a prolonged period of time (column 5, lines 1 – 17). Shih et al. defines "Depot" as a localized site in the body containing concentrated active agents or drugs, such as gels, implants, micro spheres, matrices, particles, etc. (column 7, lines 33 – 36).
The biodegradable block copolymers therein can be one or more copolymers such as ABA (instant (a) ABA triblock copolymer (EXAMPLE 4 for PLGA-PEG-PLGA triblock copolymer (PLGA is poly(lactic-co-glycolic)acid) or BAB type triblock copolymers, AB type diblock copolymers (instant (b) diblock copolymer, wherein B in AB diblock copolymer is an encapped polyethylene glycol; see column 13, Example 6 which contains mPEG-PLA). See column 1, lines 10-21; column 9, lines 4-30. Shih et al. teaches that in ABA, and AB block copolymer A-block can be PLA or PLGA polyester. See column 5, lines 20-45. Shih et al. teaches that the biodegradable polyesters are synthesized from monomers selected from the group consisting of D,L-lactide, D-lactide, L-lactide, D,L-lactic acid, and copolymers thereof such as PLGA (see column 5, lines 20-36, for PLGA which is poly(lactic-co-glycolic acid); EXAMPLE 4, EXAMPLE 11). See column 5, lines 20-45. Shih et al. teaches that the weight percentage of the A block is between 20 % to 99 %. See column 4, lines 27-42. Shih et al. teaches that the ABA-type or BAB-type triblock copolymers, or AB-type diblock copolymers have a weight average molecular weight of between 2400 and 4999 and the block copolymers have 50 to 65 % by weight of hydrophobic A block comprising biodegradable polyester and 35 to 49.9 % by weight of the hydrophilic B block consisting of polyethylene glycol (PEG) i.e. teaches instant repeat units ranges of v, w, x, y, z (a block copolymer with 4999 Daltons molecular weight can contain 2499 Da of A block (polyester block, approximately 27 units of lactide) and 2499 Da of B block (PEG block)). See column 9, lines 31-42. Shih et al. teaches that the therapeutic effects of the drug can be optimized by controlling the copolymer molecular weights, compositions, and the relative ratios of the hydrophilic and hydrophobic blocks, ratios of drug to copolymer, copolymer concentration in the final administered dosage form. See column 6, lines 4-12. The compositions therein can be administered parenterally. See column 7, lines 29-32; claim 15. Shih et al. teaches composition comprising PEG derivative, PLGA-PEG-PLGA triblock copolymer, water, active agent Zinc insulin. See EXAMPLEs 8, 9. Drugs that can be used therein are any bioactive agent that have limited solubility or dispersibility in aqueous or hydrophilic environment. See column 10, lines 32-55. Drugs therein can be gastrointestinal affecting drugs.
Shih teaches that organic solvents such as N-methyl-2-pyrrolidone (NMP), dimethyl sulfoxide are known to be employed in drug delivery compositions. See column 1, lines 51-55.
Shih et al. does not exemplify a composition comprising a mixture of mPEG-PLGA diblock copolymer and PLGA-PEG-PLGA triblock copolymer as drug carrier i.e. does not provide an example.
Shih et al. does not teach the instant particular ratios of diblock and triblock copolymers in the compositions therein.
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ a mixture of a mPEG-PLGA diblock copolymer and a PLGA-PEG-PLGA triblock copolymer as the drug carriers because Shih et al. teaches that biodegradable block copolymers therein as drug carriers can be one or more copolymers such as ABA (instant (a) ABA triblock copolymer wherein A is polyester such as PLGA, B is PEG; column 13, TABLE 2) or BAB type triblock copolymers; AB type diblock copolymers wherein B in AB diblock copolymer is an encapped polyethylene glycol and A is polyester such as PLGA. One of ordinary skill in the art at the time of invention would have motivated to employ a mixture of a mPEG-PLGA diblock copolymer and a PLGA-PEG-PLGA triblock copolymer as the drug carriers with reasonable expectation of success of obtaining a homogenous drug delivery composition for parenteral administration with enhanced therapeutic effect.
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ the particular ratios of biodegradable triblock copolymer (ABA) (a) to diblock copolymer (AB)(b). One having ordinary skill in the art at the time the invention was made would have been motivated to determine the particular ratios of biodegradable triblock copolymer (ABA) to diblock copolymer (AB) in the drug delivery compositions, since the optimization of amounts of known agents, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art.
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ the particular amounts of biodegradable triblock copolymer (ABA), diblock copolymer (AB) and the drug. One of ordinary skill in the art at the time of invention would have been motivated to employ the particular amounts of biodegradable triblock copolymer (ABA), diblock copolymer (AB), and the drug in the drug delivery compositions, since the optimization of effective amounts of known agents, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art.
It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980).
Further, it would have been obvious to a person of ordinary skill in the art to optimize the number of repeat units of polyethylene glycol and polyester PLGA to obtain copolymers that are insoluble in aqueous environment. One having ordinary skill in the art at the time the invention was made would have been motivated to determine or optimize the number of repeat units of polyethylene glycol and polyester PLGA to obtain copolymers that are insoluble in aqueous environment and obtain a drug delivery composition that is insoluble in aqueous environment, since the optimization of repeat units of monomers, is considered well in the competence level of an ordinary skilled artisan in polymer science, involving merely routine skill in the art.
It would have been obvious to a person of ordinary skill in the art to obtain copolymers with polyethylene glycol chain molecular weight as in instant claim 13; the polyester repeat units to ethylene oxide molar ratios of triblock and diblock copolymers as in instant claim 17.
Further, Shih et al. teaches that the therapeutic effects of the drug can be optimized by controlling the copolymer molecular weights, compositions, and the relative molar ratios of the hydrophilic and hydrophobic blocks, ratios of drug to copolymer, copolymer concentration in the final administered dosage form.
The examiner respectfully points out the following from MPEP 2144.05: "When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also In re Peterson, 315 F. 3d at 1330, 65 USPQ 2d 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." MPEP 2114.04.
Further, Shih et al., render instant composition obvious, the recitations in claims 9, 10, 20 are the properties of the composition, since Shih et al., render the composition obvious, the property of such a claimed composition will also be rendered obvious by the prior art teachings.
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ N-methyl-2-pyrrolidone (NMP) as organic solvent in a drug delivery composition containing diblock and triblock copolymers, and a drug taught by Shih et al. One of ordinary skill in the art at the time of invention would have been motivated to prepare a drug delivery composition comprising a drug, diblock and triblock copolymers taught by Shih et al. in an organic solvent such as NMP because Shih teaches that organic solvents such as N-methyl-2-pyrrolidone (NMP) are known to be employed in drug delivery compositions.
2)Claims 28 and 30 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Shih et al. (US 7,649,023, PTO-892 of record in the Parent Application) as applied to claims 9, 11, 12, 13, 14, 15, 16, 17, 18, 19, 27 and 29, and further in view of Feng-Jing Chen (US 2003/0077297, PTO-892 of record).
Shih et al. is applied as discussed above.
Shih et al. does not teach the particular drug risperidone in the composition therein.
Feng-Jing Chen teaches pharmaceutical composition for delivery of active agents. Active agents therein can be gastrointestinal agents such as risperidone. See para [0083].
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ pharmaceutically active agent such as risperidone as the drug in a drug delivery composition containing diblock and triblock copolymers because Shih et al. teaches that drugs can be chemotherapeutic agents for parasitic infections, drugs that influence inflammatory responses, chemotherapeutic agents for microbial diseases, gastrointestinal affecting drugs etc., and risperidone is a gastrointestinal affecting drug. One of ordinary skill in the art at the time of invention would have been motivated to employ pharmaceutically active agent such as risperidone as the drug in the drug delivery composition comprising diblock, and triblock copolymers with reasonable expectation of obtaining a drug delivery composition for parenteral administration with enhanced therapeutic effect.
Response to Arguments
Applicant argues:
- Applicant argues that “The biodegradable drug composition of the present invention, is an injectable liquid at room temperature, insoluble in an aqueous solution, and forms an implant when injected into the aqueous environment of the body. This is the exact opposite of the teachings of Shih, which requires that the composition can be reconstituted in water or an aqueous solution to form a homogenous solution or a uniform colloidal system within 0.01 minutes to 180 minutes.” Therefore, it is clear from the disclosure of Shih that the essence of the invention relates to "the discovery of PEG, PEG derivatives or mixtures thereof that can, in minutes, efficiently accelerate the dissolution of the biodegradable block copolymer drug carriers into an aqueous medium" (emphasis added).
- It would not have been obvious to a person of ordinary skill to obtain a biodegradable composition as defined in current claims that is insoluble in water and comprise a diblock copolymer and a triblock copolymer in a certain weight ratio and an organic solvent, since Shih does not provide any guidance to use such a combination. In particular, as previously mentioned, Shih does not disclose any example having more than one copolymer and teaches away from using organic solvent and instead recommends using aqueous based system.
- The presently claimed invention shows unexpected improved results in that the combination of triblock and diblock achieve a good control of initial burst and modulate the release rate of the drug over time with the formation of a biodegradable depot upon administration. As such, the invention as claimed is neither taught nor in any way suggested by Shih. Feng-Jing Chen, which is relied on the for the general teaching of risperidone as an API fails to compensate for the deficiencies of Shih.
- Applicant’s remarks that “In the Notice of Allowance dated 12/17/2009 the Examiner stated the following of why the application was allowable over the prior art: The invention of Rathi et al is directed to similar biodegradable block copolymer drug carriers which upon parenteral administration form a gel at body temperature (Abstract US6117949). In contrast the instant invention is liquid and free flowing upon parenteral administration and this distinguishes the instant invention from the cited art”.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive because: as set forth above, Shih teaches drug delivery liquid compositions comprising one or more biodegradable block copolymers of structure AB and ABA, where the structures of block copolymers are identical or similar to instantly claimed, where the composition can be insoluble in aqueous environment but soluble in liquid PEG. Said composition can be administered as is, and form a drug containing depot for slow drug release after being administered, wherein "depot" is a localized site in the body containing concentrated active agents or drugs, such as implant. Shih et al. does teach that it is well known to use water soluble organic solvents for PLGA based drug delivery systems. Further, it is pointed out that Shih et al. teaches that the composition comprises liquid polyethylene glycol which meets “pharmaceutically acceptable organic solvent” criteria.
Thus, Shih teaches all the components of instantly claimed composition, where the optimization of repeat units of monomers, is considered well in the competence level of an ordinary skilled artisan in polymer science, involving merely routine skill in the art, moreover Shih suggests combining said components into a composition, thereby rendering the instant composition obvious.
Regarding the argument about reference of Rathi, it is not persuasive because US6117949 or Rathi et al. was not employed as prior art in the current rejection. It is not clear which Application Notice of Allowance Applicant is referring to.
Regarding the argument that Shih does not disclose any example having more than one copolymer, it is not persuasive because as set forth above, Shih discloses all the components of instantly claimed composition and suggests their combination. It has been well-established that consideration of a reference is not limited to the preferred embodiments or working examples, but extends to the entire disclosure for what it fairly teaches, when viewed in light of the admitted knowledge in the art, to person of ordinary skill in the art. See M.P.E.P. § 2123.
Therefore, applicant’s arguments are not persuasive and the rejection of claims 9, 11 – 19 and 27 – 30 as obvious over teachings of Shih is maintained.
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 obviousness-type 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 LongL 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 conflicting 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. Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
1)Claims 9, 11-19, 27 and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7-30 of U.S. Patent No. 11,666,527, in view of Shih et al. (US 7,649,023, PTO-892 of record). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims are drawn to a biodegradable drug delivery composition comprising: (a) a single biodegradable triblock copolymer having the formula: A v-B w-A x wherein A is a polyester poly(lactic-co-glycolide) (PLGA) and B is polyethylene glycol and v, w and x are the number of repeat units ranging from 4 to 1090 or 6 to 1090 and v=x or v#x;(b) a single biodegradable diblock copolymer having the formula: C y-A z wherein A is a polyester poly(lactic-co-glycolide) (PLGA) and C is an end-capped polyethylene glycol and y and z are the number of repeat units ranging from 3 to 237 or 7 to 371, wherein the ratio of the biodegradable triblock copolymer of (a) and the biodegradable CA diblock copolymer of (b) is 1: 3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19 in said biodegradable drug composition; and (c) at least one pharmaceutically active principle.
Claims of ‘527 are drawn to injectable biodegradable drug delivery composition comprising: (i) a mixture of at least three different block copolymers, wherein each block copolymer is: (a) a biodegradable triblock copolymer having the formula: Av-Bw-Ax, wherein A is a polyester and B is polyethylene glycol and v and x are the number of repeat units ranging from 1 to 3,000 and w is the number of repeat units ranging from 3 to 300 and v=x or v#x; or (b) a biodegradable diblock copolymer having the formula: Cy-Az wherein A is a polyester and C is an end-capped polyethylene glycol and y and z are the number of repeat units with y ranging from 2 to 250 and z ranging from 1 to 3,000; and wherein the mixture comprises at least one (a) and at least one (b); and the weight ratio of the sum of the biodegradable triblock copolymers of (a) and the sum of the biodegradable diblock copolymers of (b) is 1:19 to 5:1; and wherein for at least one of the copolymers according to (a) or (b) A is poly(lactic-co-glycolic acid) (PLGA); and (ii) at least one pharmaceutically active ingredient; wherein the composition further comprises mPEGy-PLGAz (see claim 8); the composition further comprises a pharmaceutically acceptable vehicle (see claim 12).
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ a mixture of a mPEG-PLGA diblock copolymer and a PLGA-PEG-PLGA triblock copolymer as the drug carriers because 1) ‘527 teaches an injectable biodegradable drug delivery composition comprising: (i) a mixture of at least three different block copolymers, wherein each block copolymer is: (a) a biodegradable triblock copolymer having the formula: Av-Bw-Ax, wherein A is a polyester and B is polyethylene glycol and v and x are the number of repeat units ranging from 1 to 3,000 and w is the number of repeat units ranging from 3 to 300 and v=x or v#x; or (b) a biodegradable diblock copolymer having the formula: Cy-Az wherein A is a polyester and C is an end-capped polyethylene glycol and y and z are the number of repeat units with y ranging from 2 to 250 and z ranging from 1 to 3,000; and wherein the mixture comprises at least one (a) and at least one (b); and the weight ratio of the sum of the biodegradable triblock copolymers of (a) and the sum of the biodegradable diblock copolymers of (b) is 1:19 to 5:1; and wherein for at least one of the copolymers according to (a) or (b) A is poly(lactic-co-glycolic acid) (PLGA); and (ii) at least one pharmaceutically active ingredient; wherein the composition further comprises mPEGy-PLGAz (see claim 8); the composition further comprises a pharmaceutically acceptable vehicle (see claim 12). One of ordinary skill in the art at the time of invention would have motivated to employ a mixture of a mPEG-PLGA diblock copolymer and a PLGA-PEG-PLGA triblock copolymer as the drug carriers with reasonable expectation of success of obtaining a homogenous drug delivery composition for parenteral administration with enhanced therapeutic effect.
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ the particular ratios of biodegradable triblock copolymer (ABA) (a) to diblock copolymer (AB)(b). One having ordinary skill in the art at the time the invention was made would have been motivated to determine the particular ratios of biodegradable triblock copolymer (ABA) to diblock copolymer (AB) in the drug delivery compositions, since the optimization of amounts of known agents, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art.
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ the particular amounts of biodegradable triblock copolymer (ABA), diblock copolymer (AB) and the drug. One of ordinary skill in the art at the time of invention would have been motivated to employ the particular amounts of biodegradable triblock copolymer (ABA), diblock copolymer (AB), and the drug in the drug delivery compositions, since the optimization of effective amounts of known agents, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art.
It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980).
Shih et al. is applied as discussed above. Shih et al. teaches that the therapeutic effects of the drug can be optimized by controlling the copolymer molecular weights, compositions, and the relative molar ratios of the hydrophilic and hydrophobic blocks, ratios of drug to copolymer, copolymer concentration in the final administered dosage form.
Further, it would have been obvious to a person of ordinary skill in the art to optimize the number of repeat units of polyethylene glycol and polyester PLGA to obtain copolymers that are insoluble in aqueous environment. One having ordinary skill in the art at the time the invention was made would have been motivated to determine or optimize the number of repeat units of polyethylene glycol and polyester PLGA to obtain copolymers that are insoluble in aqueous environment and obtain a drug delivery composition that is insoluble in aqueous environment, since the optimization of repeat units of monomers, is considered well in the competence level of an ordinary skilled artisan in polymer science, involving merely routine skill in the art.
It would have been obvious to a person of ordinary skill in the art to obtain copolymers with polyethylene glycol chain molecular weight as in instant claim 13; the polyester repeat units to ethylene oxide molar ratios of triblock and diblock copolymers as in instant claim 17. Further, Shih et al. teaches that the therapeutic effects of the drug can be optimized by controlling the copolymer molecular weights, compositions, and the relative molar ratios of the hydrophilic and hydrophobic blocks, ratios of drug to copolymer, copolymer concentration in the final administered dosage form.
The examiner respectfully points out the following from MPEP 2144.05: "When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also In re Peterson, 315 F. 3d at 1330, 65 USPQ 2d 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." MPEP 2114.04.
2)Claims 9, 11-19, 27 and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of co-pending Application No. 18/283,350 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims are drawn to a biodegradable drug delivery composition comprising: (a) a single biodegradable triblock copolymer having the formula: A v-B w-A x wherein A is a polyester poly(lactic-co-glycolide) (PLGA) and B is polyethylene glycol and v, w and x are the number of repeat units ranging from 4 to 1090 or 6 to 1090 and v=x or v#x;(b) a single biodegradable diblock copolymer having the formula: C y-A z wherein A is a polyester poly(lactic-co-glycolide) (PLGA) and C is an end-capped polyethylene glycol and y and z are the number of repeat units ranging from 3 to 237 or 7 to 371, wherein the ratio of the biodegradable triblock copolymer of (a) and the biodegradable CA diblock copolymer of (b) is 1: 3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19 in said biodegradable drug composition; and (c) at least one pharmaceutically active principle.
Claims of ‘350 are drawn to pharmaceutical composition comprising (a) a triblock copolymer having the formula: Av-B-Ax wherein A is a polyester such as poly(lactic-co-glycolide) (PLGA), B is polyethylene glycol, v and x are numbers of repeat units ranging from 1 to 3,000 and w is a number of repeat units ranging from 3 to 300 and v=x or v#x in an amount of from about 3 w/w % to 25 w/w % of the total composition; (b) a diblock copolymer having the formula: Cy-Az wherein A is a polyester poly(lactic-co-glycolide) (PLGA), C is an end-capped polyethylene glycol, and y and z are numbers of repeat units with y ranging from 2 to 250 and z ranging from 1 to 3,000 in an amount of from about 3 w/w % to 35 w/w% of the total composition; (c) a therapeutic protein which is an Interleukin-1 antagonist in an amount of from about 0.5 w/w % to 25 w/w % of the total composition; (d) optionally one or more stabilizer compounds in an amount of from about 0.25 w/w % to 15 w/w % of the total composition; and (e) organic solvent in an amount of from about 50 w/w % to 80 w/w % of the total composition.
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ the particular ratios of biodegradable triblock copolymer (ABA) (a) to diblock copolymer (AB)(b). One having ordinary skill in the art at the time the invention was made would have been motivated to determine the particular ratios of biodegradable triblock copolymer (ABA) to diblock copolymer (AB) in the drug delivery compositions, since the optimization of amounts of known agents, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art.
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ the particular amounts of biodegradable triblock copolymer (ABA), diblock copolymer (AB) and the drug. One of ordinary skill in the art at the time of invention would have been motivated to employ the particular amounts of biodegradable triblock copolymer (ABA), diblock copolymer (AB), and the drug in the drug delivery compositions, since the optimization of effective amounts of known agents, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art.
It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980).
Further, it would have been obvious to a person of ordinary skill in the art to optimize the number of repeat units of polyethylene glycol and polyester PLGA to obtain copolymers that are insoluble in aqueous environment. One having ordinary skill in the art at the time the invention was made would have been motivated to determine or optimize the number of repeat units of polyethylene glycol and polyester PLGA to obtain copolymers that are insoluble in aqueous environment and obtain a drug delivery composition that is insoluble in aqueous environment, since the optimization of repeat units of monomers, is considered well in the competence level of an ordinary skilled artisan in polymer science, involving merely routine skill in the art.
It would have been obvious to a person of ordinary skill in the art to obtain copolymers with polyethylene glycol chain molecular weight as in instant claim 13; the polyester repeat units to ethylene oxide molar ratios of triblock and diblock copolymers as in instant claim 17.
The examiner respectfully points out the following from MPEP 2144.05: "When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also In re Peterson, 315 F. 3d at 1330, 65 USPQ 2d 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." MPEP 2114.04.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
3)Claims 9, 11-19 and 27-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 9-28 of U.S. Patent No. 11,801,217, in view of Shih et al. (US 7,649,023, PTO-892 of record). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims are drawn to a biodegradable drug delivery composition comprising: (a) a single biodegradable triblock copolymer having the formula: A v-B w-A x wherein A is a polyester poly(lactic-co-glycolide) (PLGA) and B is polyethylene glycol and v, w and x are the number of repeat units ranging from 4 to 1090 or 6 to 1090 and v=x or v#x;(b) a single biodegradable diblock copolymer having the formula: C y-A z wherein A is a polyester poly(lactic-co-glycolide) (PLGA) and C is an end-capped polyethylene glycol and y and z are the number of repeat units ranging from 3 to 237 or 7 to 371, wherein the ratio of the biodegradable triblock copolymer of (a) and the biodegradable CA diblock copolymer of (b) is 1: 3 to 1:8 or 1:1 to 1:19 or 3:2 to 1:19 in said biodegradable drug composition; and (c) at least one pharmaceutically active principle.
Claims of ‘217 are drawn to an injectable biodegradable drug delivery composition comprising: (i) a mixture of at least three different block copolymers, wherein each block copolymer is: (a) a biodegradable triblock copolymer having the formula: Av-Bw-Ax wherein A is a polyester and B is polyethylene glycol and v and x are the number of repeat units ranging from 1 to 3,000 and w is the number of repeat units ranging from 3 to 300 and v=x or vex; or (b) a biodegradable diblock copolymer having the formula: Cy-Az wherein A is a polyester and C is an end-capped polyethylene glycol and y and z are the number of repeat units with y ranging from 2 to 250 and z ranging from 1 to 3,000; and wherein the mixture comprises at least one (a) and at least one (b); and the weight ratio of the sum of the biodegradable triblock copolymers of (a) and the sum of the biodegradable diblock copolymers of (b) is 1:19 to 5:1; and (ii) at least one pharmaceutically active ingredient; wherein the composition further comprises at least one organic solvent; wherein the at least one pharmaceutically active ingredient is risperidone.
Shih et al. is applied as discussed above.
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ a mixture of a mPEG-PLGA diblock copolymer and a PLGA-PEG-PLGA triblock copolymer as the drug carriers because 1) ‘217 teaches an injectable biodegradable drug delivery composition comprising: (i) a mixture of at least three different block copolymers, wherein each block copolymer is: (a) a biodegradable triblock copolymer having the formula: Av-Bw-Ax wherein A is a polyester and B is polyethylene glycol and v and x are the number of repeat units ranging from 1 to 3,000 and w is the number of repeat units ranging from 3 to 300 and v=x or vex; or (b) a biodegradable diblock copolymer having the formula: Cy-Az wherein A is a polyester and C is an end-capped polyethylene glycol and y and z are the number of repeat units with y ranging from 2 to 250 and z ranging from 1 to 3,000; and wherein the mixture comprises at least one (a) and at least one (b); and the weight ratio of the sum of the biodegradable triblock copolymers of (a) and the sum of the biodegradable diblock copolymers of (b) is 1:19 to 5:1; and (ii) at least one pharmaceutically active ingredient and 2) Shih et al. teaches that biodegradable block copolymers therein as drug carriers can be one or more copolymers such as ABA (instant (a) ABA triblock copolymer wherein A is polyester such as PLGA, B is PEG; column 13, TABLE 2) or BAB type triblock copolymers; AB type diblock copolymers wherein B in AB diblock copolymer is an encapped polyethylene glycol and A is polyester such as PLGA. One of ordinary skill in the art at the time of invention would have motivated to employ a mixture of a mPEG-PLGA diblock copolymer and a PLGA-PEG-PLGA triblock copolymer as the drug carriers with reasonable expectation of success of obtaining a homogenous drug delivery composition for parenteral administration with enhanced therapeutic effect.
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ the particular ratios of biodegradable triblock copolymer (ABA) (a) to diblock copolymer (AB)(b). One having ordinary skill in the art at the time the invention was made would have been motivated to determine the particular ratios of biodegradable triblock copolymer (ABA) to diblock copolymer (AB) in the drug delivery compositions, since the optimization of amounts of known agents, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art.
It would have been obvious to a person of ordinary skill in the art at the time of invention to employ the particular amounts of biodegradable triblock copolymer (ABA), diblock copolymer (AB) and the drug. One of ordinary skill in the art at the time of invention would have been motivated to employ the particular amounts of biodegradable triblock copolymer (ABA), diblock copolymer (AB), and the drug in the drug delivery compositions, since the optimization of effective amounts of known agents, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art.
It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980).
Further, it would have been obvious to a person of ordinary skill in the art to optimize the number of repeat units of polyethylene glycol and polyester PLGA to obtain copolymers that are insoluble in aqueous environment. One having ordinary skill in the art at the time the invention was made would have been motivated to determine or optimize the number of repeat units of polyethylene glycol and polyester PLGA to obtain copolymers that are insoluble in aqueous environment and obtain a drug delivery composition that is insoluble in aqueous environment, since the optimization of repeat units of monomers, is considered well in the competence level of an ordinary skilled artisan in polymer science, involving merely routine skill in the art.
It would have been obvious to a person of ordinary skill in the art to obtain copolymers with polyethylene glycol chain molecular weight as in instant claim 13; the polyester repeat units to ethylene oxide molar ratios of triblock and diblock copolymers as in instant claim 17. Further, Shih et al. teaches that the therapeutic effects of the drug can be optimized by controlling the copolymer molecular weights, compositions, and the relative molar ratios of the hydrophilic and hydrophobic blocks, ratios of drug to copolymer, copolymer concentration in the final administered dosage form.
The examiner respectfully points out the following from MPEP 2144.05: "When the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimal or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also In re Peterson, 315 F. 3d at 1330, 65 USPQ 2d 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." MPEP 2114.04.
Further, Shih et al., render instant composition obvious, the recitations in claims 9, 10, 20 are the properties of the composition, since Shih et al., render the composition obvious, the property of such a claimed composition will also be rendered obvious by the prior art teachings.
Response to Arguments
Applicant argues:
- The claims of the '527 patent and '271 patent fail to suggest the specific combination of features are recited in the present claims. The claims of both the '527 and 217 patents require "a mixture of at least three different block copolymers", wherein each of the three block copolymers is either a triblock copolymer of (a) or a diblock copolymer of (b). (emphasis added) In addition, with the compositions of the '527 patent and '217 patent, with the triblock copolymers of (a), V and X range from 1 to 3,000 and W ranges from 3 to 300 and with the diblock copolymer of (b), y and Z range from 2 to 250 and Z ranges from 1 to 3,000. The '217 patent further specifically requires "2, 3 or 4 different biodegradable diblock copolymers" (claim 1). The present invention as claimed, on the other hand, requires the features that: 1) There is only a single biodegradable triblock copolymer and only a single biodegradable diblock copolymer; 2) V, W and x in the triblock copolymer range from 4 to 1090 or 6 to 1090 3) y and Z in the diblock copolymer from 3 to 237 or 7 to 371.
- The Examiner points to Shih as teaching that it would be obvious to optimize the compositions by controlling the molecular weights, compositions and ratios of the hydrophilic and hydrophobic blocks etc. However, as discussed above the compositions of Shih are liquid or free flowing both before and after administration. As such, modifying the polymer compositions as guided by Shih would not achieve the instantly claimed compositions and the compositions of the invention cannot be said to be obvious over the claims of either of the '527 patent or the '217 patent.
- With regard to co-pending Application No. 18/283,350, Applicant requests that this rejection be held in abeyance until the claims in one of the two applications are otherwise allowable.
Examiner’s response:
Applicant's arguments have been fully considered but they are not persuasive because: as set forth above, instantly claims are directed to an injectable biodegradable drug delivery composition comprising only a single biodegradable triblock copolymer and only a single biodegradable diblock copolymer of structure: Av-Bw-Ax (e.g. PLGA-PEG-PLGA) and Cy-Az (e.g. mPEG-PLGA). The patented claims of ‘527 and '217 are directed to an injectable biodegradable drug delivery composition comprising: (i) a mixture of at least three different block copolymers, wherein each block copolymer is: (a) a biodegradable triblock copolymer having the formula: Av-Bw-Ax (e.g. PLGA-PEG-PLGA) or (b) a biodegradable diblock copolymer having the formula: Cy-Az (e.g. mPEG-PLGA) wherein the numerical ranges of variables v, w, x, y and z overlap or fall within the instantly claimed ranges of corresponding variables, and wherein the mixture comprises at least one (a) and at least one (b). Claims of copending application No. 18/283,350 are directed to a pharmaceutical composition comprising (a) a triblock copolymer having the formula: Av-B-Ax, where A is a PLGA, B is polyethylene glycol, (b) a diblock copolymer having the formula: Cy-Az, where A is PLGA, C is an end-capped polyethylene glycol, and wherein the numerical ranges of variables v, w, x, y and z overlap or fall within the instantly claimed ranges of corresponding variables. MPEP 2144.05 states: In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). Although instant claims do not recite all the components of compositions disclosed in patents ‘527, '217 and a copending application No. 18/283,350, the “comprising” claim language does not exclude additional, unrecited elements or steps. Furthermore, Shih teaches similar composition, where biodegradable block copolymers therein as drug carriers can be one or more copolymers such as ABA (instant (a) ABA triblock copolymer wherein A is polyester such as PLGA, B is PEG or BAB type triblock copolymers; AB type diblock copolymers wherein B in AB diblock copolymer is an encapped polyethylene glycol and A is polyester such as PLGA.
Thus, the instantly claimed composition would be obvious over composition disclosed in patents ‘527, '217 and a copending application No. 18/283,350.
Regarding the argument about distinction between the composition of Shih and the instantly claimed is not persuasive, because, as set forth above Shih discloses an identical or very similar composition, where all the same or similar properties are presumably present (see 35 USC § 103 rejection section and response to arguments).
Regarding the argument about holding in abeyance the rejection over claims of co-pending application, it is not persuasive because, MPEP 804 states: If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent. Since provisional nonstatutory double patenting over claims of copending application is not the only rejection of the instant application, the argument is not found persuasive.
Therefore, applicant’s arguments are not persuasive and the rejection of claims:
9, 11-19, 27 and 29 the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 11,666,527;
9, 11-19 and 27-30 on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 11,801,217; and
the provisional rejection of claims 9, 11-19, 27 and 29 on the ground of nonstatutory double patenting as being unpatentable over claims of co-pending Application No. 18/283,350 in view of Shih is maintained.
Conclusion
Claims 9, 11 – 19 and 27 – 30 are rejected. No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/E.V.V./ Examiner, Art Unit 1691
/RENEE CLAYTOR/ Supervisory Patent Examiner, Art Unit 1691
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