DETAILED ACTION
1. The present application is being examined under the pre-AIA first to invent provisions.
INFORMATION DISCLOSURE STATEMENT
2. Information Disclosure Statement submitted 5/13/2024 is acknowledged.
Claim Rejections- 35 USC § 112 –Scope of Enablement
3. The following is a quotation of the first paragraph of 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 1-12 and 36-37 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for the composition that contains polyethylene glycol 4000 or 3350, does not reasonably provide enablement for the full scope of any polyethylene glycol molecular weight. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. Furthermore, while being enabled for treating schizophrenia, bipolar disorder, or depression, the specification does not reasonably provide enablement for the full scope of preventing schizophrenia, bipolar disorder, or depression.
The claims are directed to an injectable preparation comprising a composition comprising a poorly soluble drug, a dispersion medium, and a suspending agent the suspending agent being polyethylene glycol and carboxymethyl cellulose or a salt thereof, the composition having a viscosity of 40 pascal or more in at least one point in the shear rate range of 0.01 to 0.02 s-1 and having a viscosity of 0.2 pascal or less in at least one point in the shear rate of 900 to 1,000 s-1, as measured by a rheometer at 25 oC. The claims are further directed to methods of treating or preventing a recurrence of schizophrenia, bipolar disorder, or depression.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, "Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue', not 'experimentation'" (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations" (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are directed to an injectable preparation comprising a composition comprising a poorly soluble drug, a dispersion medium, and a suspending agent the suspending agent being polyethylene glycol and carboxymethyl cellulose or a salt thereof, the composition having a viscosity of 40 pascal or more in at least one point in the shear rate range of 0.01 to 0.02 s-1 and having a viscosity of 0.2 pascal or less in at least one point in the shear rate of 900 to 1,000 s-1, as measured by a rheometer at 25 oC. Thus, the claims taken together with the specification imply that any polyethylene glycol molecular weight and any sodium carboxymethyl cellulose would be usable. The scope of claim 1 reasonably encompasses such a broad spectrum of materials that it is unreasonable to believe, on its face, that any particular chemical compound could be used for forming the pharmaceutical composition with the desired viscosity properties, in the absence of supporting scientific data or references in the disclosures to the contrary. The claims are further directed to methods of treating or preventing a recurrence of schizophrenia, bipolar disorder, or depression. Prevention is suggested to include a level of protection against, up to and including complete protection against the development of a disease or condition which is unsupported by the disclosure. Giving the claims their broadest reasonable interpretation the term “prevention” includes any measure taken prior to the onset or occurrence of a disease or condition which precludes its coming into existence, absolutely and in all cases. Therefore, preventing reperfusion renders the scope of the claims unreasonably broad.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
The state of the art is replete in terms of injectable perpetrations containing polyethylene glycol (PEG) and carboxymethyl cellulose (CMC). There is no evidence in the prior art that the instant composition of claim 1, encompassing a broad range of every molecular weight of PEG and would be usable in forming the injectable preparation with the desired viscosity. There is no evidence in the prior art that the instant composition would be usable as a preventative composition, particularly for preventing a reoccurrence of schizophrenia, bipolar disorder, or depression. Preventing” connotes an absolute absence of a condition which cannot reasonably be achieved with regard to reperfusion or in medicine generally, with few exceptions (such as vaccines to prevent the development of pathogen-borne illnesses). In addition, there is no definitive method by which to determine whether a patient will develop a particular condition and, thus, be in need of preventive therapy. This is distinguished from preventing the relapse or recurrence of certain conditions, in which case an objective basis may exist to identify patients at risk of disease or infection, and could reasonably be construed as treatment. Prior to the initial onset or occurrence, however, even if a patient can be identified as having known risk factors for a condition, there is no certainty that the patient would in fact develop the condition. Further, the failure of a disease, infection, or condition to develop cannot reliably be attributed to the claimed active agent(s). The non-development of a condition such as reperfusion may be due to other factors such as lifestyle, or genetics. In this sense, in the context of preventing a condition, the level of unpredictability is extremely high
(5) The relative skill of those in the art:
One of skill in the art would typically have a graduate degree in the field of endeavor such as M.D. or a PhD. MPEP 2141.03 states (in part), "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. At 1396, 82 USPQ2d at 1396. The "hypothetical person having ordinary skill in the art' to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art." Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988).
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
It should also be noted that only PEG with molecular weights of 3350 and 4000 were used and the molecular weight of CMC was not specified.
There is no guidance provided by the inventor which species would be usable to obtain the desired composition with the desired properties. The Examples in the affidavit presented only teach PEG 3350 and PEG 4000 and don’t even teach CMC. As can be seen by comparative Example 4, simply having both components won’t yield the viscosity. Consequently, a burdensome amount of research would be required by one of ordinary skill in the art.
The amount of direction or guidance is minimal or non-existent with regards to preventing the reoccurrence of schizophrenia, bipolar disorder, or depression. Thus, with respect to the instant composition, there is a substantial gap between treatment and prevention especially when no working examples are provided. Consequently, it would require undue experimentation for the skilled artisan to discover how to make and use the instant invention in order to prevent the reoccurrence of schizophrenia, bipolar disorder, or depression.
(G) The presence or absence of working examples: The specification does not disclose any evidence that bone and/or cartilaginous infections or osteomyelitis be prevented
(8) The quantity of experimentation necessary:
A burdensome amount of research would be required by one of ordinary skill in the art to determine what molecular weight PEG and what molecular weight CMC in combination of what drug and amounts that would yield an injectable preparation that would have the desired viscosity. One of ordinary skill in the art would have to conduct a myriad number of experiments comprising guessing which molecular weight PEG and CMC to use in combination with which compound, to make the composition usable. Consequently, a burdensome amount of research would be required by one of ordinary skill in the art to bridge this gap.
In the instant case, there is a substantial gap between treatment and prevention in the case of schizophrenia, bipolar disorder, or depression. Consequently, a burdensome amount of research would be required by one of ordinary skill in the art to bridge this gap. Because "preventing” a condition by the administration of an active agent cannot be objectively measured or achieved with any certainty, coupled with a lack of guidance and direction provided by the instant disclosure, a skilled artisan could not practice the invention commensurate with the full scope of the claims without undue experimentation. The rejection in regards to the methods of preventing can be overcome by amending the claims to omit the term “preventing.”
CONCLUSION
Given the complete lack of direction in applicant's instant disclosure, the amount of experimentation required to realize the full scope of claims 1-10 is clearly undue. Applicants have not described how one would know what molecular weight PEG are suitable for use, in such full, clear, concise, and exact terms as to enable any person skilled in the art to do so. While the applicant is enabled for PEG 4000 and PEG 3350, applicant is not enabled for the broad scope of any molecular weight PEG and CMC and any compound. Furthermore, given the complete lack of guidance in applicant's instant disclosure, regarding preventing the reoccurrence of schizophrenia, bipolar disorder, or depression, an undue amount experimentation is required to realize the full scope of the claims. Applicant has not described how to completely prevent the reoccurrence if schizophrenia, bipolar disorder, or depression, in such full, clear, concise, and exact terms as to enable any person skilled in the art to do so.
Claim Rejections- 35 USC § 112 1st Paragraph Written Description
4. The following is a quotation of the first paragraph of 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 1-12 and 36-37 are rejected under 35 U.S.C. 112, 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(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Costello, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, the claims are directed to an injectable preparation comprising a composition comprising a poorly soluble drug, a dispersion medium, and a suspending agent the suspending agent being polyethylene glycol and carboxymethyl cellulose or a salt thereof, the composition having a viscosity of 40 pascal or more in at least one point in the shear rate range of 0.01 to 0.02 s-1 and having a viscosity of 0.2 pascal or less in at least one point in the shear rate of 900 to 1,000 s-1, as measured by a rheometer at 25 oC
(1) Level of skill and knowledge in the art:
The level of skill and knowledge in the art is replete with regards to injectable preparations containing PEG and CMC. MPEP 2141.03 states (in part), “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR International Co. v. Teleflex Inc., 127 S.Ct. 1727, 167 LEd2d 705, 82 USPQ2d 1385, 1397 (2007). “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At 1396, 82 USPQ2d at 1396. The “hypothetical person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988).
(2) Partial structure:
The specification and affidavit show that PEG 3350 and PEG 4000 in combination with CMC obtain an injectable perpetration with the desired viscosity. However, neither the specification nor the art indicate a relationship between the molecular weight of the PEG and CMC and the desired viscosity. Would other PEG with differing molecular weights still obtain the desired viscosity? Furthermore, the Examples all use 5 % CMC would varying the amounts alter the viscosity? The Examples use PEG in .1, 1 and 10 weight percent but there is no relationship between the different PEG and amounts included and their effect on the viscosity. Furthermore, the affidavit in copending application 14396,380 has shown the desired viscosity is not obtained when no drug is present but one skilled in the art would not know if different drugs would yield the desired property.
The specification also does not recite how one would configure the composition such that it obtains the desired viscosity (What molecular weight PEG or CMC, what amounts and what drugs?). There is no indication of how one would configure such a formulation to obtain such viscosity. There is no guidance as to what relative amounts, what molecular weights of PEG and CMC in combination of the drug to use to impart the desired viscosity. For these reasons, the pending claims lack a written description.
(3) Physical and/or chemical properties and (4) Functional characteristics:
The physical and/or chemical properties of the composition which provide for all the functional properties claimed are not determinable because no specific components to the composition are disclosed. It is not disclosed which molecular weight PEG, CMC and drug, and what relative amounts, to use in order to achieve the desired viscosity.
(5) Method of making the claimed invention:
Although the claims may recite some functional characteristics (i.e., PEG and CMC), the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond those compounds specifically disclosed in the examples in the specification. There is little guidance in the specification as to what molecular weight of PEG and CMC and what relative amount would obtain the desired viscosity. The specific Examples presented in the affidavit do not disclose the CMC molecular weight and one skilled in the art would not know which one to select to obtain the desired viscosity. Furthermore, different active ingredients in both formulations and the amounts of the PEG varied.
As stated supra, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that the claims are broad and generic, with respect to all possible compounds encompassed by the claims. Although the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure of the compounds beyond those compounds specifically disclosed in the examples in the specification. Moreover, the specification lacks sufficient variety of species to reflect this variance in the genus. While having written description of the claimed therapeutics and compounds identified in the specification tables and/or examples, the specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 112
5. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-4, and 10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 10 recite as measured by rheometer however, it is not clear under what conditions as the temperature at which it is measured can affect the viscosity. It is suggested to amend to as measured by a rheometer at 25 C. The dependent claims 3 and 4 do not cure the deficiency of claim 1.
Claim Rejections - 35 USC § 102
6. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1-4 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by
Hiraoka et al. (US 2010/0196486).
Hiraoka et al. (US 2010/0196486) (hereinafter Hiraoka et al.) teach injectable
formulations of aripiprazole containing suspending agent polyvinylpyrrolidone (abstract
and Is 0094 and 0153). The composition is dissolved in water for injection (i.e.,
dispersion medium) (1 0116). With regards to the limitation that the "composition has a
viscosity of 40 Pas or more in at least one point in the shear rate range of 0.01 to 0.02 s
1 and having a viscosity of 0.2 Pas or less in at least one point in the shear range of 900
to 1,000 s⁻¹, as measured by a rheometer", Hiraoka et al. teach all the same structural
features as claimed and since the properties of a composition result from the structural
features present in the composition it would have these properties. Furthermore, the
office does not have the facilities and resources to provide the factual evidence needed
in order to establish that the product of the prior art does not possess the same
material, structural and functional characteristics of the claimed product. In the absence
of evidence to the contrary, the burden is on the applicant to prove that the claimed
product is different from those taught by the prior art and to establish patentable
differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte
Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Claim Rejections - 35 USC § 103
7. The following is a quotation of pre-AIA 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-5, 8-12 and 36-37 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Jain et al. (US 2010/0015195) in view of Nakagawa et al. (US 2012/0091022).
Jain et al. (hereinafter Jain et al.) teach in situ gel depots for injection (i.e., sol-gel) that contain a poorly soluble drug (aripiprazole), water and suspending agent (polyethylene glycol and sodium carboxymethyl cellulose) (Examples 3 and 6, claims 33, 36, 39, 49, and 50). Although Examples 3 and 6 teach propylene glycol, claim 50 teaches polyethylene glycol and it would have been prima facie obvious to one skilled in the art at the time the invention was filed to use polyethylene glycol as component 2 (claim 50). Jain et al. teach various methods of administration such as intramuscularly (para 0003).
Jain et al. teach viscosity enhancing agent can be polyvinylpyrrolidone or polyalkylene glycols, and sodium carboxymethyl cellulose and mixtures (¶ 0052).
Jain et al. does not teach the primary particle diameter of 0.5 to 30 um in a concentration of 200 mg/ml to 600 mg/ml.
Nakagawa et al. (US 2012/0091022) (hereinafter Nakagawa et al.) teach sustained release injectable formulations containing drugs such as aripiprazole where the microparticles have a mass median diameter of at least about 10 um and wherein the formulation contains active ingredient contained in amount from 50 mg/mL to about 600 mg/mL (¶s 0003, 0004, and 0041). Nakagawa et al. teach it is preferred to keep the mean particle size of an active ingredient as small as possible (¶ 0012). Nakagawa et al. teach that when the mean particle size thereof was too small, the sustained release for a long period could not be attained; whereas when the particles of bigger mean particle size were used so that the sustained release for a long period could be attained, then an injection needle was clogged with the particles, thus it was found that such bigger particles was difficult for be injected. Nakagawa et al. teach mean particles sizes of about 4 µm to 55 µm (¶ 0023).The method in which the composition is administered (i.e., administered once or twice per month or every three months) is given little patentable weight to a composition claim because the structural features of the composition are the same. Nakagawa et al. disclose the therapeutic agent, aripiprazole has psychotropic activity as is useful for treating diseases such as schizophrenia (para 0002).
Jain et al. does not specifically teach that there is a mean secondary particle diameter that is up to but not exceeding three times the mean primary particle diameter thereof however, Nakagawa et al. teach particle sizes as a result effective variable where if they are too small it is not ideal for sustained release however, if they are too large then this presents particles that are not easily injected and clog the injection apparatus. It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to optimize the size of the particles in a composition for injection. One would have been motivated to stay away from using too large or too small particle sizes in order to obtain the desired sustained release and avoid sizes that would clog the injection apparatus.
8. Claims 5-7 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Jain et al. (US 2010/0015195) in view of Nakagawa et al. (US 2012/0091022) as applied to claims 1-5, 8-12, 36-37 above, and further in view of Frincke et al. (US 2009/0258850), Cheng et al. (US 2007/0110784) and Turp et al. (US 2010/0137292).
Jain et al. in view of Nakagawa et al. have been discussed supra. Frincke et al. teach suspending agents which include polyethylene glycol and carboxymethylcellulose.
Cheng et al. (US 2007/0110784) (hereinafter Cheng et al.) teach polyethylene glycol (PEG) and carboxymethylcellulose (CMC) in amounts of 0.5 and 1 % w/v respectively. Both PEG and CMC resulted in a concentration-dependent reduction in gel syneresis (i.e., increasing the additive concentration reduced synersis). This effect is presented to occur due to an increase in the negative entropy of mixing for the TRG solution resulting from the ability of the PEG and CMC to structure water and represents a convenient method for tailoring gel volume retention (¶ 0097).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to optimize the amount of PEG/CMC. One would have been motivated to do so in order to tailor gel volume retention.
With regards to the concentration of PVP, Turp et al. (US 2010/0137292) (hereinafter Turp et al.) disclose Meloxicam (poorly water soluble drug) with propylene glycol and povidone K-17 (polyvinylpyrrolidone) present at 2 mg/ml (suspending agent) and water for injection (tables 2-4). Since the same suspending agent is taught with the same molecular weight (povidone K-17) in the same amounts as the suspending agents as disclosed for use in the specification, it is reasonable to conclude that with regards to the limitation that "the composition having a viscosity of 40 Pas or more in at least one point in the shear range of 0.01 to 0.02 s-1 and having a viscosity of 0.2 Pas or less in at least one point in the shear range of 900 to 1,000 as measured by rheometer" which the examiner interprets to be at 25°C, that the same viscosity properties would necessarily follow since the same structural features of the composition are disclosed and there no other additional ingredients (i.e., viscosity modifying agents) included in the examples of the specification that would give rise to said viscosity beyond the suspending agents and drug. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural, and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the product is different from those taught by the prior art and to establish patentable differences. It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed have selected various combinations of various disclosed ingredients such as suspending agents (i.e., povidone K-17) and poorly water insoluble drug (meloxicam) in a dispersion medium (water) to arrive compositions yielding no more than one would expect from such an arrangement.
9. Claims 5, 7, 9, 11, and 36-37 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hiraoka et al. (US 20100196486) and Boyd et al. (US 2008/0214995).
Hiraoka et al. (US 20100196486) (hereinafter Hiraoka et al.) disclose suspensions containing aripiprazole (abstract). Aripiprazole is used for treating schizophrenia (para 0081). One, two or more suspending agents are disclosed for use that include polyethylene glycol (e.g., carbowaxs 3350) which are PEG 3350.Other suspending agents disclosed include carboxymethyl cellulose (para 0091). The formulations include water for injection. The aripiprazole has mean particle size of 1 to 10 microns (para 0104) and the concentration is from 10 to 400 mg/ml (para 0119). The injections are formulated intramuscularly (para 0153). The viscosity range of carboxymethyl cellulose or the sodium salt thereof may be suitably selected from a wide range. Generally, the viscosity of a 4% aqueous solution at 25.degree. C. is preferably about 20 to 400 cps, particularly about 50 to 200 cps. With regards to the viscosity in at least one point in the shear rate range, it is noted the same ingredients are recited in Hiraoka (suspending agents can be on or more that include PEG 3350 and CMC) where the same therapeutic agent is taught having the same particle size and concentration where the formulation is combined with water, and thus since the structural features are disclosed applicants recitation of properties are expected to be present in such formulations.
Boyd et al. (US 2008/0214995) (hereinafter Boyd et al.) disclose formulations capable of forming a depot include ones comprised of PEG (para 0099). Thermoreversible hydrogels are of interest and include thermosensitive gel materials that exhibit a sol-to –gel transition which include polyethylene oxide and PEG (para 0008 and 0110). The formulations can be any liquid, solid or other state of matter that can be injected and preferred formulations are liquid formulations including polymers and gels (para 0062). With regards to the limitation the composition being in the form of a gel when allowed to stand, and changing to a sol when subjected to an impact, having the formulations of Hiraoka be in the form gels is obvious in view of Boyd. The fact it turns to a sol when subjected to impact is a property of the formulation and the same suspending agents are disclosed in Hiraoka (i.e., one or more such as CMC and PEG 3350. It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have the formulations of Hiraoka et al. be in the form of gels such as taught by Boyd. One would have been motivated to do so because such formulations are suitable for injection.
DOUBLE PATENTING
10. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-12 and 36-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 10517951. Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant invention and the ‘951 are drawn to injectable compositions containing suspending agent pvp, PEG and CMC the difference being the instant invention does not require all 3 compared to the ‘951 patent. The claims overlap in scope.
Claims 1-12 and 36-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11097007. Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant invention and the ‘951 are drawn to injectable compositions containing suspending agent PVP the difference being the instant invention does not require PVP. The claims overlap in scope.
Claims 1-12 and 36-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of U.S. Patent No. 11638757. Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant invention and the ‘951 are drawn to injectable compositions containing suspending agent PVP the difference being the instant invention does not require PVP. The claims overlap in scope.
CORRESPONDENCE
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Danah Al-awadi whose telephone number is (571) 270-7668. The examiner can normally be reached on 9:00 am - 6:00 pm; M-F (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DANAH AL-AWADI/Primary Examiner, Art Unit 1615
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