DETAILED ACTION
Status of Application
The response filed 05/15/2026 has been received, entered and carefully considered. The response affects the instant application accordingly:
Claims 1, 6-7, 14, 19-20, 30-32 have been amended.
Claims 8, 21, 27-28 has been cancelled.
A terminal disclaimer was filed over U.S. Pat. 11529333, U.S. Pat. 12491179, U.S. Pat. Application 17/975789, U.S. Pat. Application 18/114410.
A terminal disclaimer was filed on 05/15/2026 over U.S. Pat. 11529333, U.S. Pat. 12491179, U.S. Pat. Application 17/975789, U.S. Pat. Application 18/114410.
The terminal disclaimer over U.S. Pat. 11529333, U.S. Pat. 12491179, U.S. Pat. Application 17/975789, U.S. Pat. Application 18/114410 was approved on 05/15/2026; wherein the rejections based on these patents and applications are withdrawn.
Applicant had previously elected Group I in response to restriction requirement and for the examination.
Due to restriction, based on election of Group I, claims 14-16, 19-20, 22, 25-26 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 1, 6-7, 9, 12-16, 19-20, 22, 25-26, 30-33 are pending.
Claims 1, 6-7, 9, 12-13, 30-33 are present for examination at this time.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
All grounds not addressed in the action are withdrawn or moot as a result of amendment.
New grounds of rejection are set forth in the current office action as a result of amendment.
Priority
The claims as amended appear to have support back to the priority document.
New Grounds of Rejection
Due to the amendment of the claims the new grounds of rejection are applied:
Claim Rejections - 35 USC § 112
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.
Claim 6 is 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 claim recites “wherein the buffering agent is sodium citrate, potassium citrate, citric acid monohydrate, tri-sodium citrate dihydrate, or any combination thereof” which is unclear it depends from claim 1 which as amended no longer recites for combinations of the recited buffers and now is broader than the claim it depends from and lacks antecedent basis.
Claim 32 is 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 claims recites “wherein the buffering agent is citric acid monohydrate and tri-sodium dihydrate, wherein the citric acid monohydrate is present at about 3.7 mg/mL and the tri-sodium citrate dihydrate is present at about 3.6 mg/mL” which is unclear as it depends from claim 7 where the buffer is either citric acid monohydrate or tri-sodium citrate dihydrate but claim 32 is reciting that both citric acid monohydrate and tri-sodium citrate dihydrate must be present at the recited amounts, despite depending from a claim that where they are alternatives. It does not allow one to ascertain the metes and bounds of the claims as written. For purposes of examination, the claim is treated to have both components.
Response to Arguments:
Applicant states that applicant has amended the claim and is now not indefinite. This is fully considered but not persuasive as addressed above, the claim is unclear as it is broader that the recitations in instantly presented claim 7.
Accordingly the rejection stands.
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 6 is 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.
The claim recites “wherein the buffering agent is sodium citrate, potassium citrate, citric acid monohydrate, tri-sodium citrate dihydrate, or any combination thereof” which depends from claim 1 which as amended no longer recites for combinations of the recited buffers and now is broader than the claim it depends from and fails to further limit the claim from which it depends from. 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 32 is 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 32 recites the presence of both citric acid monohydrate and tri-sodium citrate dihydrate which depends from claim 7 which as amended is to either citric acid monohydrate or tri-sodium citrate dihydrate and no longer recites for combination of the two buffers together; wherein it is now broader than the claim it depends from and fails to further limit the claim from which it depends from. 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 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.
Claims 1, 6-7, 9, 12-13, 30-31, 33 are rejected under 35 U.S.C. 103 as being unpatentable over Gandhi et al. (WO 2011/107855) in view of Ohno et al. (WO 2017/057562) and www.mystrica.com (0.1M Citric acid-Sodium citrate buffer buffer — pH range 3.0-6.2).
CA 2999414 is the national stage entry of WO 2017/057562 and will be used as the translation. All references will be to the translation.
Rejection:
Gandhi et al. teaches an oral liquid suspension dosage form comprising actives including zonisamide and levetiracetam. The liquid suspension contains suspending stabilizers (thickening agents) like xanthan gum (up to 1-25% wt of the composition, preferably about 1-about 15%), excipients, inert pellets with seal coating and drug layer (abstract, claims 1, 4, 6-7, 10, 12-13; Page 3 line 10-Page 4 line 14, Page 5 line 1-Page 6 line 4, Page 6 line 25-28). The suspension can be aqueous and include buffers like sodium citrate and citric acid (monohydrate, example 3) and sodium phosphate and mixtures thereof – with the buffer being the preferred mixture of citric acid and sodium citrate, thickening agents (suspension stabilizers) like xanthan gum and carboxymethylcellulose or its alkali metal salt (i.e. sodium carboxymethylcellulose) and microcrystalline cellulose and mixtures thereof (up to 1-25%, preferably about 1-about 15%), sweeteners like aspartame and sucrose and sucralose, flavorings like peppermint and the exemplified strawberry (Example 2), preservatives like sodium benzoate and parabens (i.e. methyl paraben, butyl paraben) from 0.01%-5%, inert cores that are sugar spheres or other equivalents like microcrystalline cellulose), fillers like microcrystalline cellulose (about 1-about 50%), binders like sodium carboxymethylcellulose (about 0.1-about 20%), and humectants like glycerin and propylene glycol (wetting agents, Page 7 line 11-15, Page 8 line 27-Page 9 line 18, Page 10 line 13-Page 11 line 4, Page 11 line 20-26, Page 12 line 8-Page 13 line 15, Page 22, Page 23 line 15-18). The dosage form can be prepared with the therapeutic dosage of the active. Example 2 contains a coated active with HPMC (hydroxypropylmethylcellulose) in an aqueous suspension with xanthan gum, parabens (preservative), aspartame (sweetener), strawberry flavor. Example 5-6 are to pellets that utilize microcrystalline cellulose cores that are suspended in aqueous based dispersing agent with additives (see full document specifically areas cited).
While Gandhi et al. does not expressly teach an example with zonisamide, it does teach the suspension with incorporation of an active like zonisamide with various excipients and exemplifies a suspension with an active such as Example 2; wherein the formulation of the suspension like Example 2 with another active like zonisamide with the taught excipients like suspending agents such as xanthan gum, sweeteners like aspartame or sucralose, flavorings like peppermint, preservative, with the taught buffers like sodium citrate and citric acid (monohydrate example 3) are prima facie obvious with a reasonable expectation of success. It would also be prima facie obvious to optimize the amount of preservative like the taught sodium benzoate within the taught range of 0.01%-5% and arrive at the claimed values (i.e. about 0.1%=about 1mg/ml, about 0.2%=about 2mg/ml) as a means of attaining the desired therapeutic profile absent evidence of criticality for the claimed values.
Gandhi et al. does not expressly teach the amount of zonisamide or the recited pH range, but does teach the inclusion of the therapeutic dose of the active in the suspension and teaches the inclusion of buffers including a preferred mixture of citric acid and sodium citrate.
Ohno et al. teaches that zonisamide can be formulation for oral route including suspension [124] and the effective dose is 1 mg to 2000 mg specifically ranges of 10mg to 1000mg and 20mg to 600mg [124-125], and be 0.1-70% of the formulation [126].
www.mystrica.com teaches that a citrate buffer contains citric acid monohydrate and trisodium citrate dihydrate (also known as sodium citrate dihydrate and sodium citrate) and water, and that it produces a pH range of 3.0-6.2.
Wherein it would be obvious to one or ordinary skill in the art before the effective filing date of the claimed to invention incorporate zonisamide within the known effective range and to incorporate the known components of a citrate buffer as suggested by Ohno et al. and www.mystrica.com teaches and produce the claimed invention; as it is prima facie obvious to optimize the amount of zonisamide within the known effective range and arrive at the claimed values with a reasonable expectation of success absent evidence of criticality for the claimed amount of zonisamide. It is also prima facie obvious to incorporate the known components of a citrate buffer that is taught to be included in the composition and adjust the pH of the taught citrate buffer within its known range and arrive at the claimed values with a reasonable expectation of success absent evidence of criticality. It is also prima facie obvious to optimize around the taught pH based on the known pH range of the preferred citrate buffer and arrive at the recited values absent evidence of criticality for the claimed values. As the suspension contains the recited structural components claimed (zonisamide, suspending agent, water, recited buffers, preservative, and sweetener, pH), the composition would be expected to have the same impurity profile at the recited conditions.
Response to Arguments:
Applicant's arguments are centered on the assertion that Gandhi is to a sustained release oral liquid suspension with sustained release pellets and does not have an example with zonisamide, that Mystrica only teaches a citrate buffer with citric acid monohydrate and trisodium citrate dihydrate and water, that while Ohno disclose a range for zonisamide (10mg-1000mg, 20-600mg) that the zonisamide solutions are with DMSO and does not teach liquid formulations for oral administration, that there is no guidance or motivation to combine the references to arrive at the claimed zonisamide suspension with the recited impurity and stability profile, and the assertion for secondary considerations.
This is fully considered but not persuasive. Applicant’s arguments to Ohno and Mystrica are against the reference individually, and one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The assertion that there is no guidance or motivation to combine the references is not persuasive as addressed by the obviousness rejection presented above. The assertion that Gandhi et al. is to a sustained release formulation is not persuasive as the claims are open to the inclusion of any component (“comprising”) and teaches an oral suspension with known components for suspensions including one or more actives and co-administration of the actives that can be together or separate. The assertion that there is no example in Gandhi et al. and the other references is not persuasive as the argument that the prior art reference must have an example is an assertion that a reference should be a singular teaching with a working example to be applicable for obviousness which is not the standard for obviousness. Obviousness is not restricted to a single working example or to a single reference as obviousness may be to a combination of references as addressed in the rejection above. The teachings of Gandhi et al. establishes known oral liquid suspensions comprising actives including zonisamide and levetiracetam, with known excipients including suspending/thickening/viscosity agents like xanthan gum and carboxymethylcellulose and microcrystalline cellulose and mixtures thereof, buffers like sodium citrate and citric acid (monohydrate, example 3), sweeteners, and preservatives; wherein it is prima facie obvious to formulate and exemplify the taught suspension with the taught active with a reasonable expectation of success. Ohno and www.mystrica.com are presented merely to show the known dosage and effective range of zonisamide and the known pH range of citrate buffers respectively wherein optimization of the zonisamide within the known effective range and the pH for citrate buffers is prima facie obvious to attain the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed amount of zonisamide and pH range. As the suspension contains the recited structural components claimed (i.e. zonisamide, xanthan gum, CMC, water, recited buffers, preservative, pH), the composition would be expected to have the same impurity profile at the recited conditions which is dictated by the structural components as taught by the instant disclosure.
As for the assertion for secondary considerations, the Salinardi declaration and Mosher declaration are directed to the specific formulation of the ZONISADE formulation which has be patented in the grandchild application and not commensurate in scope with the instant claims which is broader. The instant claims do not contain all the components that contribute to the profile of the specific formulation of the ZONISADE formulation which has been patented/allowed in the great-grandparent (16/354764) and grandparent (17975789) applications; wherein each component that contributed to the profile of the specific formulation of the ZONISADE formulation presented in the declaration had to be present in the claim to be commensurate in scope with the showing (which is the case in the patented/allowed grandparent and great-grandparent applications).
Accordingly, the rejection stands.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Gandhi et al. (WO 2011/107855) in view of Ohno et al. (WO 2017/057562) and www.mystrica.com (0.1M Citric acid-Sodium citrate buffer buffer — pH range 3.0-6.2) as applied to claims 1, 6-7, 9, 12-13, 30-31, 33 above, further in view of Rowe et al. (Citric Acid Monohydrate) and Rowe et al. (Sodium Citrate Dihydrate).
Rejection:
The teachings of Gandhi et al. in view of Ohno et al. and www.mystrica.com are addressed above.
Gandhi et al. in view of Ohno et al. and www.mystrica.com do not expressly teach the amount of citric acid monohydrate (about 3.7mg/ml= about 0.37%) or trisodium citrate dihydrate (also known as sodium citrate dihydrate and sodium citrate, about 3.6mg/ml= about 0.36%) but does teach the inclusion of citrate buffers like citric acid monohydrate and the preferred mixture of citric acid and sodium citrate.
Rowe et al. teaches that citric acid monohydrate is known to be used as a buffer from 0.1-2% (Table 1).
Rowe et al. teaches that sodium citrate dihydrate is known to be used as a buffer from 0.3-2% (Table 1).
Wherein it would be prima facie obvious to one of skill in the art before the effective filing date of the claimed invention to incorporate the known components of a citrate buffer that is taught to be included in the composition in their known useful range and to optimize within the range to attain the desired therapeutic profile/pH and arrive at the claimed values with a reasonable expectation of success absent evidence of criticality for the claimed amounts.
Response to Arguments:
Applicant’s arguments are those presented to Gandhi et al.in view of Ohno et al. and www.mystrica.com which are addressed above.
Applicant’s remaining argument to Rowe et al. (Citric Acid Monohydrate) and Rowe et al. (Sodium Citrate Dihydrate) are that they do not teach the claimed zonisamide formulations with the recited stability which is to the reference individually which is not persuasive as one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Accordingly the rejection stands.
Claims 1, 6-7, 9, 12-13, 30-31, 33 are rejected under 35 U.S.C. 103 as being unpatentable over Heller et al. (US. Pat. Pub. 2017/0172961) in view of Dainippon Sumitomo Pharma (Notice of launching of a new Parkinson's disease drug "TRERIEF”) and Gandhi et al. (WO 2011/107855).
Rejection:
Heller et al. teaches a pharmaceutical suspension for oral delivery containing drug particles, water, surfactant, thickeners, and physically stable (abstract, [12, 14-15, 20, 26, 30, 75]. The drug particle formulations include levodopa (L-DOPA) and a preferred pH of about 3.5-7.5 like about 4.5 and buffers like citrate buffer solution such as with citric acid monohydrate and phosphate buffers like sodium phosphate buffer solution, and one or more drugs for treating Parkinson’s disease with the levodopa and can be at concentrations including 0.1mg/ml-20mg/ml (claim 1, Table 6, [26, 30, 191, 497-506, 562, 568, 594-595, 651-652, 1142, 1150, 1164, 1239]). The drugs can be co-administered where the actives can be formulated together or separately (when separately zonisamide is the only active [101, 195]). The thickeners include celluloses like microcrystalline cellulose (MCC) and carboxymethylcellulose ([35, 71, 75,504], also suspending agents). The suspensions include preservatives like sodium benzoate from 0.1-1.0%wt.[25, 423, 506], sweeteners like sucralose and saccharine sodium, and flavorings ([423], Table 24, [1251]). It can also include glycerol, ethanol, propylene glycol, and polyethylene glycol (wetting agents [71], see full document specifically areas cited).
Heller et al. does not expressly teach the amount of microcrystalline cellulose and carboxymethylcellulose or the inclusion of xanthan gum or zonisamide but does teach the inclusion of additional drugs for treating Parkinson’s disease with the levodopa [502] that can be formulated separately and co-administered [101], and viscosity agents including carboxymethylcellulose and microcrystalline cellulose. Heller et al. also does not specify the type of flavoring but does teach the inclusion of flavorings.
Dainippon Sumitomo Pharma teaches that zonisamide is useful for Parkinson’s disease and should be combined with levodopa (Page 1, Page 2 –Indications, and Dosage and Administration).
Gandhi et al. teaches that known thickening/viscosity agents (also called suspension stabilizers) include xanthan gum, carboxymethylcellulose or its alkali metal salt (sodium CMC), microcrystalline cellulose and mixtures thereof; and are known to be present from up to 1-25% preferably about 1-about 15%wt.; and that known flavor agents include peppermint flavor and the exemplified strawberry flavor in Example 2 (Page 9 line 11-18, Page 10 line 13-Page 11 line 2, Page 12 line 19-21, Example 2 Page 20).
Wherein it would be obvious to one of skill in the art before the effective filing date of the claimed invention to incorporate zonisamide in the composition and xanthan gum and optimize the amount of thickeners (i.e. MCC/CMC) as suggested by Dainippon Sumitomo Pharma and Gandhi et al. and produce the claimed invention; as it is prima facie obvious to include zonisamide as Heller teaches the inclusion of additional drugs for treating Parkinson’s disease with the levodopa which can be formulated separately and co-administered, and Dainippon Sumitomo Pharma expressly teaches the two drugs to be in combination for Parkinson’s disease, and optimize the amount of the drug within the taught range (i.e. 0.1-20mg/ml) with a reasonable expectation of success absent evidence of criticality for the claimed value. It is also obvious to incorporate known viscosity/thickening/suspending agents at their known ranges as disclosed by Gandhi, as Heller teaches their inclusion the optimization of viscosity agents (i.e. mixtures like MCC/CMC) within their known range to attain the desired therapeutic profile is prima facie obvious with a reasonable expectation of success absent evidence of criticality for the claimed value (i.e. 2%=20mg/ml MCC/CMC). It is also prima facie obvious to incorporate another known viscosity agent (mixture) like xanthan gum with MCC and sodium CMC (carboxymethylcellulose alkali salt) for its known purpose and additive effect in their known range or even simple substitution of one known viscosity agent for another for its known purpose, in their known range and optimize within the range and arrive at the claimed values (i.e. about 2% MCC/CMC and about 3mg/ml xanthan) as a means of attaining the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed thickener and amount (i.e. 2%=20mg/ml MCC/CMC. It is also prima facie obvious to incorporate known flavorings like strawberry as Heller teaches the inclusion of flavorings with a reasonable expectation of success absent evidence of criticality for the claimed flavor.
While the prior art does not teach the exact claimed dependent values for the sodium benzoate or pH, they are embraced by the taught range of Heller wherein it would be prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize within the taught range and arrive at the claimed values as a means of attaining the desired therapeutic profile (degree of preservation, pH) with a reasonable expectation of success absent evidence of criticality for the claimed values. As the suspension contains the recited structural components claimed (i.e. zonisamide, suspending agent (i.e. xanthan gum, CMC/MCC), water, sucralose, buffers, sodium benzoate, pH), the composition would be expected to have the same impurity profile at the recited conditions.
Response to Arguments:
Applicant arguments are centered on the assertion that Heller does not teach or suggest a formulation of a second drug to be co-administered separately with levodopa nor a separate formulation of the second drug to be physically stable or with the recited components, that Dainippon is to a tablet, that Gandhi is to a sustained release suspension with pellets where it does not cure the deficiencies of Heller and Dainippon, that the reference do not provide an example of the oral formulation of zonisamide, assertion for secondary considerations, that the references do not teach a stable zonisamide suspension with the recited impurity profile at the recited conditions which is unexpected, that there is no context/disclosure to combine them with a reasonable success.
This is fully considered but not persuasive as Applicant's arguments to Heller and Dainippon and Gandhi are against the references individually, and one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Dainippon is presented merely to show that zonisamide is known to be useful for Parkinson’s disease and should be combined with levodopa, Gandhi is presented merely to show known thickening/suspending agents. The assertion that Heller does not teach/suggest a formulation of a second drug to be co-administered separately is not persuasive as contrary to Applicant’s assertion, Heller expressly teaches the drug suspension comprising levodopa with the various components and expressly teaches/defines co-administration with additional actives that can be formulated together or separately wherein it expressly teaches/suggests the formulation to contain additional actives (together in the formulation) or separately (separate drugs in the formulation). With regards to the assertion that the references do not have an example of the claimed suspension is again to the references individually as addressed above, and Applicant’s argument is an assertion for anticipation of the reference which is not the basis for obviousness rejection as presented above.
As for the assertion for secondary considerations, the Salinardi declaration and Mosher declaration are directed to the specific formulation of the ZONISADE formulation which has be patented in the grandchild application and not commensurate in scope with the instant claims which is broader. The instant claims do not contain all the components that contribute to the profile of the specific formulation of the ZONISADE formulation which has be patented in the grandchild application and it is noted that the Mosher declaration submitted on 08/19/2024 demonstrates that the flavorings impact the profile wherein each component that contributed to the profile of the specific formulation of the ZONISADE formulation presented in the declaration had to be present in the patented claim to be commensurate in scope with the showing which is the case in the patented grandchild application. Applicant’s remaining arguments that the prior art does not provide a reasonable expectation of success for arriving at the claimed formulation with the recited stability is fully considered but not persuasive. Formulation of a known oral suspension of levodopa in combination with zonisamide for its additive effect for Parkinson’s as separate formulations as addressed by Heller (wherein zonisamide is the only active in separate formulations) is prima facie obvious with a reasonable expectation of success absent evidence of criticality for the claimed amount of zonisamide or specific excipients. As the prior art rejection is directed to the formulation of the suspension and as the suspension contains the recited structural components claimed – the composition would be expected to have the same impurity profile at the recited conditions absent evidence to the contrary as Heller establishes and expectation of long term stability and the instant disclosure addresses that the zonisamide suspension with these structural components would have the recited impurity profile at the recited conditions.
Accordingly, the rejection stands.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Heller et al. (US. Pat. Pub. 2017/0172961) in view of Dainippon Sumitomo Pharma (Notice of launching of a new Parkinson's disease drug "TRERIEF”) and Gandhi et al. (WO 2011/107855) as applied to claims 1, 6-7, 9, 12-13, 30-31, 33 above, further in view of www.mystrica.com (0.1M Citric acid-Sodium citrate buffer buffer – pH range 3.0-6.2) and Rowe et al. (Citric Acid Monohydrate) and Rowe et al. (Sodium Citrate Dihydrate).
Rejection:
The teachings of Heller in view of Dainippon Sumitomo Pharma and Gandhi et al. are addressed above.
Heller in view of Dainippon Sumitomo Pharma and Gandhi et al. do not expressly teach the amount of citric acid monohydrate (about 3.7mg/ml= about 0.37%) or trisodium citrate dihydrate (sodium citrate dihydrate, about 3.6mg/ml= about 0.36%) but does teach the inclusion of citrate buffers including components like citric acid monohydrate.
www.mystrica.com teaches that a citrate buffer contains citric acid monohydrate and trisodium citrate dihydrate and water.
Rowe et al. teaches that citric acid monohydrate is known to be used as a buffer from 0.1-2% (Table 1).
Rowe et al. teaches that sodium citrate dihydrate is known to be used as a buffer from 0.3-2% (Table 1).
Wherein it would be prima facie obvious to one of skill in the art before the effective filing date of the claimed invention to incorporate the known components of a citrate buffer that is taught to be included in the composition in their known useful range and to optimize within the range to attain the desired therapeutic profile/pH and arrive at the claimed values with a reasonable expectation of success absent evidence of criticality for the claimed amounts.
Response to Arguments:
Applicant's arguments are those to Heller in view of Dainippon and Gandhi which are addressed above. Applicant’s remaining arguments are to Rowe et al. (Citric Acid Monohydrate) and Rowe et al. (Sodium Citrate Dihydrate) for not teaching the claimed zonisamide formulation with the claimed stability which is to the reference individually which is fully considered but not persuasive as one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Accordingly, the rejection stands.
Claims 1, 6-7, 9, 12-13, 30-31, 33 are rejected under 35 U.S.C. 103 as being unpatentable over Heller et al. (US. Pat. Pub. 2017/0172961) in view of Dainippon Sumitomo Pharma (Notice of launching of a new Parkinson's disease drug "TRERIEF”) and Namburi et al. (U.S. Pat. Pub. 2008/0260837) and Medisca (Suggested Flavoring Reference Chart).
Rejection:
Heller et al. teaches a pharmaceutical suspension for oral delivery containing drug particles, water, surfactant, thickeners, and physically stable (abstract, [12, 14-15, 20, 26, 30, 75]. The drug particle formulations include levodopa (L-DOPA) and a preferred pH of about 3.5-7.5 like about 4.5 and buffers like phosphate buffers and citrate buffer solution such as with citric acid monohydrate, and one or more drugs for treating Parkinson’s disease with the levodopa and can be at concentrations including 0.1mg/ml-20mg/ml (claim 1, [26, 30, 191, 497-506, 562, 568, 594-595, 651-652, 1150, 1239]). The drugs can be co-administered where the actives can be formulated together or separately (when separately zonisamide is the only active [101, 195]). The thickeners include celluloses like microcrystalline cellulose (MCC) and carboxymethylcellulose ([35, 71, 75,504], also suspending agents). The suspensions include preservatives like sodium benzoate from 0.1-1.0%wt. [25, 423, 506], sweeteners like sucralose and saccharine sodium, and flavorings [423, 1251 Table 24]. It can also include glycerol, ethanol, propylene glycol, and polyethylene glycol (wetting agents [71], see full document specifically areas cited).
Heller et al. does not expressly teach the inclusion of zonisamide or the amount of viscosity agent (i.e. CMC/MCC or xanthan gum) but does teach the inclusion of additional drugs for treating Parkinson’s disease with the levodopa [502] that can be formulated separately and co-administered [101], and viscosity agents including carboxymethylcellulose and microcrystalline cellulose. Heller et al. also does not specify the type of flavoring but does teach the inclusion of flavorings.
Dainippon Sumitomo Pharma teaches that zonisamide is useful for Parkinson’s disease and should be combined with levodopa (Page 1, Page 2 –Indications, and Dosage and Administration).
Namburi et al. teaches that known viscosity/suspending/thickening agents include xanthan gum, carboxymethylcellulose sodium, microcrystalline cellulose and mixtures thereof; and are known to be present from about 0.05-about 5% [20].
Medisca teaches that flavorings are known for taste masking and masking drug classes which include raspberry, tutti frutti, peppermint oil, and strawberry.
Wherein it would be obvious to one of skill in the art before the effective filing date of the claimed invention to incorporate zonisamide and strawberry flavoring in the composition and optimize the amount of viscosity agents including incorporating xanthan gum as suggested by Dainippon Sumitomo Pharma and Namburi et al. and produce the claimed invention; as it is prima facie obvious to include zonisamide as Heller teaches the inclusion of additional drugs for treating Parkinson’s disease with the levodopa which can be formulated separately and co-administered, and Dainippon Sumitomo Pharma expressly teaches the two drugs to be in combination for Parkinson’s disease, and optimize the amount of the drug within the taught range (i.e. 0.1-20mg/ml) with a reasonable expectation of success absent evidence of criticality for the claimed value. It is also obvious to incorporate known viscosity/thickening/suspending agents at their known ranges as disclosed by Namburi, as Heller teaches their inclusion and the optimization of viscosity agents (i.e. mixtures like MCC/CMC) within their known range to attain the desired therapeutic profile is prima facie obvious with a reasonable expectation of success absent evidence of criticality for the claimed value of (2%=20mg/ml MCC/CMC). It is also prima facie obvious to incorporate another known viscosity agent (mixture) like xanthan gum with MCC and sodium CMC (carboxymethylcellulose alkali salt) or even simple substitution of one known viscosity agent for another for its known purpose in their known range is prima facie obvious with a reasonable expectation of success; and to optimize within the taught range for the viscosity agents (i.e. MCC/CMC, xanthan gum, xanthan gum/MCC/CMC) and arrive at the claimed range (i.e. about 0.3%=3mg/ml xanthan, about 2%=20mg/ml MCC/CMC) as a means of attaining the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed values. It is also prima facie obvious to incorporate a known flavoring for its known purpose with a reasonable expectation of success absent evidence of criticality for the claimed flavor.
While the prior art does not teach the exact claimed dependent values for the sodium benzoate, they are embraced by the taught range of Heller wherein it would be prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize within the taught range and arrive at the claimed values as a means of attaining the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed values. As the suspension contains the recited structural components claimed (i.e. zonisamide, suspending agent (i.e. xanthan gum, CMC/MCC), water, sucralose, buffers, sodium benzoate, pH), the composition would be expected to have the same impurity profile at the recited conditions.
Response to Arguments:
Applicant arguments are centered on the assertion that Heller does not teach or suggest a formulation of a second drug to be co-administered separately with levodopa nor a separate formulation of the second drug to be physically stable or with the recited components, that Dainippon is to a tablet, that Namburi is to viscosity/suspending/thickening agents and exemplify suspensions of ibuprofen/acetaminophen/guaifenesin, where it does not cure the deficiencies of Heller and Dainippon, that the reference do not provide an example of the oral formulation of zonisamide, assertion for secondary considerations, that the references do not teach a stable zonisamide suspension with the recited impurity profile at the recited conditions which is unexpected, that there is no context/disclosure to combine them with a reasonable success.
This is fully considered but not persuasive as Applicant's arguments to Heller and Dainippon and Namburi are against the references individually, and one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Dainippon is presented merely to show that zonisamide is known to be useful for Parkinson’s disease and should be combined with levodopa, Namburi is presented merely to show known thickening/suspending agents. The assertion that Heller does not teach/suggest a formulation of a second drug to be co-administered separately is not persuasive as contrary to Applicant’s assertion, Heller expressly teaches the drug suspension comprising levodopa with the various components and expressly teaches/defines co-administration with additional actives that can be formulated together or separately wherein it expressly teaches/suggests the formulation to contain additional actives (together in the formulation) or separately (separate drugs in the formulation). With regards to the assertion that the references do not have an example of the claimed suspension is again to the references individually as addressed above, and Applicant’s argument is an assertion for anticipation of the reference which is not the basis for obviousness rejection as presented above.
As for the assertion for secondary considerations, the Salinardi declaration and Mosher declaration are directed to the specific formulation of the ZONISADE formulation which has be patented in the grandchild application and not commensurate in scope with the instant claims which is broader. The instant claims do not contain all the components that contribute to the profile of the specific formulation of the ZONISADE formulation which has be patented in the grandchild application and it is noted that the Mosher declaration submitted on 08/19/2024 demonstrates that the flavorings impact the profile wherein each component that contributed to the specific formulation of the ZONISADE formulation presented in the declaration had to be present in the patented claim to be commensurate in scope with the showing which is the case in the patented grandchild application. Applicant’s remaining arguments that the prior art does not provide a reasonable expectation of success for arriving at the claimed formulation with the recited stability is fully considered but not persuasive. Formulation of a known oral suspension of levodopa in combination with zonisamide for its additive effect for Parkinson’s as separate formulations as addressed by Heller (wherein zonisamide is the only active in separate formulations) is prima facie obvious with a reasonable expectation of success absent evidence of criticality for the claimed amount of zonisamide or specific excipients. As the prior art rejection is directed to the formulation of the suspension and as the suspension contains the recited structural components claimed – the composition would be expected to have the same impurity profile at the recited conditions absent evidence to the contrary as Heller establishes and expectation of long term stability and the instant disclosure addresses that the zonisamide suspension with these structural components would have the recited impurity profile at the recited conditions.
Accordingly, the rejection stands.
Claim 32 is rejected under 35 U.S.C. 103 as being unpatentable over Heller et al. (US. Pat. Pub. 2017/0172961) in view of Dainippon Sumitomo Pharma (Notice of launching of a new Parkinson's disease drug "TRERIEF”) and Namburi et al. (U.S. Pat. Pub. 2008/0260837) and Medisca (Suggested Flavoring Reference Chart) as applied to claims 1, 6-7, 9, 12-13, 30-31, 33 above, further in view of www.mystrica.com (0.1M Citric acid-Sodium citrate buffer buffer – pH range 3.0-6.2) and Rowe et al. (Citric Acid Monohydrate) and Rowe et al. (Sodium Citrate Dihydrate).
Rejection:
The teachings of Heller in view of Dainippon Sumitomo Pharma and Namburi et al. and Medisca are addressed above.
Heller in view of Dainippon Sumitomo Pharma and Namburi et al. and Medisca do not expressly teach the amount of citric acid monohydrate (about 3.7mg/ml= about 0.37%) or trisodium citrate dihydrate (sodium citrate dihydrate, about 3.6mg/ml= about 0.36%) but does teach the inclusion of citrate buffers including components like citric acid monohydrate.
www.mystrica.com teaches that a citrate buffer contains citric acid monohydrate and trisodium citrate dihydrate and water.
Rowe et al. teaches that citric acid monohydrate is known to be used as a buffer from 0.1-2% (Table 1).
Rowe et al. teaches that sodium citrate dihydrate is known to be used as a buffer from 0.3-2% (Table 1).
Wherein it would be prima facie obvious to one of skill in the art before the effective filing date of the claimed invention to incorporate the known components of a citrate buffer that is taught to be included in the composition in their known useful range and to optimize within the range to attain the desired therapeutic profile/pH and arrive at the claimed values with a reasonable expectation of success absent evidence of criticality for the claimed amounts.
Response to Arguments:
Applicant's arguments are those to Heller in view of Dainippon and Namburi which are addressed above. Applicant’s remaining arguments are to Rowe et al. (Citric Acid Monohydrate) and Rowe et al. (Sodium Citrate Dihydrate) for not teaching the claimed zonisamide formulation with the claimed stability which is to the reference individually which is fully considered but not persuasive as one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Accordingly, the rejection stands.
Conclusion
Claims 1, 6-7, 9, 12-13, 30-33 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GIGI GEORGIANA HUANG whose telephone number is (571)272-9073. The examiner can normally be reached Monday-Thursday 9:00-5:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/GIGI G HUANG/Primary Examiner, Art Unit 1613
Prosecution Insights