Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a 371 of PCT/BR2020/050346 (08/31/2020) with foreign priority claim to BRAZIL 102020010933-2 (05/29/2020).
NEW 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.
Claims 1-11, 19-26 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention.
Applicant amended the claims to add new language such as the following in claim 1:
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and in claim 6:
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however, “retains” appears nowhere in the original filing. Applicant has not pointed to support for the new claim language, there does not appear to be support for the language in the original filing, one of skill in the art would not recognize that such a scope was possessed based on the original filing. In particular, nothing is disclosed about how “retains” would apply to the polymer matrix such that one of skill in the art would know what Applicant intends to claim with such language in this context. A claim containing a limitation which does not have a basis in the original disclosure is properly rejected under 35 U.S.C. 112 as failing to comply with the written description requirement. Ex parte Grasselli, 231 USPQ 393 (Bd. App. 1983), aff’d. mem., 738 F. 2d 453 (Fed. Cir. 1984). The examiner could not locate support for such a new limitation and there does not appear to be a written description of the limitation in the application. See Hyatt v. Dudas, 492 F.3d 1365, 1370, 83 USPQ2d 1373, 1376 (Fed. Cir. 2007) (holding that "[MPEP] § 2163.04 (I)(B) as written is a lawful formulation of the prima facie standard for a lack of written description rejection."). Thus, the independent claims and those that depend therefrom are rejected.
As per MPEP 2163 II A: With respect to newly added or amended claims, applicant should show support in the original disclosure for the new or amended claims. See, e.g., Hyatt v. Dudas, 492 F.3d 1365, 1370, n.4 (Fed. Cir. 2007) (citing MPEP § 2163.04 which provides that a "simple statement such as ‘applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘___’ in the application as filed’ may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported."); see also MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure.").
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Jenkins (US20070104792) in view of Melder (US20090196900) and Fritz et al. (US20080226723).
Jenkins teaches nanoparticulate tadalafil formulations (Title, Abstract, claim 1) including a solid dosage form ([0024]), including subcutaneous ([0034], [0161]) and extended release ([0035]) form. Jenkins teaches examples including compositions where tadalafil is 5-50% w/w and a polymer such as PVP at 0.1-50% ([0135]-[0137]). Jenkins teaches the compositions are useful for treating erectile dysfunction ([0024][0028]).
Although Jenkins teaches weight ranges that encompass the instant invention, Jenkins does not specifically teach the composition of tadalafil in the amount of 25 to 250 mg and the polymer at between 1 and 20% of tadalafil (i.e. 0.25 mg to 50 mg polymer).
Melder teaches an implantable device comprising tadalafil with a biocompatible polymer carrier (Abstract, claims 1-8, [0018]) for use in treating erectile dysfunction ([0030]-[0031]). Melder teaches the tadalafil-polymer device comprises particles ([0041], claim 4). Melder teaches the polymer is bioabsorbable, with examples of poly-lactic acid ([0042]: “bioabsorbable polymer depending on the desired rate of release or the desired degree of polymer stability. Bioabsorbable polymers that could be used include poly(L-lactic acid)”). Similarly, Fritz teaches implantable particles comprising tada[la]fil (claims 8-9; [0049]; [0104]) for treating erectile dysfunction.
Regarding claim 1, one of ordinary skill in the art following Jenkins in view of Melder and Fritz would have considered formulations of the well-known active pharmaceutical (API) tadalafil including subcutaneous implants using well-known techniques as suggested by Jenkins and also taught by Melder to form an implantable device comprising a bioabsorbable polymer. One of ordinary skill in the art would readily considered optimizing the formulation including the amounts of the tadalafil and the polymer to improve the efficacy and delivery of the API. Such optimization of a results effective variable is considered routine in the art and well within one of ordinary skill in the art’s technical grasp such that forming a composition comprising a particle of between 25-250 mg tadalafil and 1-20% bioabsobable polymer would be obvious. Thus, one of ordinary skill in the art would have arrived at the claimed invention with a reasonable expectation of success.
Regarding claim 2, Melder teaches the bioabsorbable polymer is poly(L-lactic acid) which one of ordinary skill in the art would have considered and arrive at the claimed invention with a reasonable expectation of success.
Regarding claim 3, Jenkins teaches the particles can have a variety of shapes, sizes, etc. ([0044]: “irrespective of their size, shape”) and specifically refers to rod-shape ([0174]-[0175]), but does not teach the specific dimensions as claimed. One of ordinary skill in the art would reasonably consider various shapes including cylindrical rod shapes of various lengths would could be utilized as an implant and optimize among the mm scale and arrive at the claimed invention with a reasonable expectation of success. MPEP 2144.04: In re Dailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966) (The court held that the configuration of the claimed disposable plastic nursing container was a matter of choice which a person of ordinary skill in the art would have found obvious absent persuasive evidence that the particular configuration of the claimed container was significant.).
Regarding claim 4, the wherein clause is interpreted as a product-by-process where and the claimed product are not limited by the steps, but only the structure implied by the steps (MPEP 2113). In this case, the obvious combination of Jenkins and Melder would result in a product with the same structure and properties as in the instant claim. Thus, the claim is obvious.
Regarding claim 5, Jenkins teaches a coating ([0130]; [0165]) as does Melder which teaches a sealing polymer coating ([0055]). Furthermore, Melder teaches bioabsorbable polymers including “poly(lactide-co-glycolide)” ([0042]) which one of ordinary skill in the art would have considered in a subcutaneous implant coating with an optimal thickness to improve delivery and arrive at the claimed invention with a reasonable expectation of success.
Regarding claim 6, as with claim 1 Jenkins in view of Melder teaches the same implant, but does not specifically teach an embodiment with a “non-bioerodible” polymer core between 1 and 20 % by weight of tadalafil. Melder does teach use of nonbiodegradable polymers ([0025]; [0041]) and removable devices ([0037]) which one of ordinary skill in the art would consider and formulate the implant with a polymer that does not degrade to facilitate removal. Such a formulation would have been an obvious variation as suggested by the combination of prior art.
Regarding claim 7 specifying the non-degradable polymer and dimensions, as with claim 6 one of ordinary skill in the art would consider and formulate the implant with a polymer that does not degrade to facilitate removal of the implant. In addition, Fritz teaches non-degradable polymers selected from acrylates to retain mechanical stability of the implant ([0079]: “methyl methacrylate (MMA) … . Most preferred is MMA. The polymer should be present in the core in a hydrated or partially hydrated (hydrogel) form. Such polymers are preferably cross-linked in order to provide suitable hydrogel properties and structure, such as enhanced non-biodegradability, and to help retain the mechanical stability of the polymer structure by resisting dissolution by water.”). Such a formulation would have been an obvious variation as suggested by the combination of prior art including among dimensions suitable for use as an implant of 0.2 to 1mm.
With each of the above claims rejected, the level of skill in the art is very high such that one of ordinary skill in the art would have considered the modification routine and arrived at the invention as claimed with a reasonable expectation of success before the effective filing date of the claimed invention.
Response to Remarks / Amendment – 35 USC 103
Applicant argument primarily addresses how each of the individual references differ from the instant claims. However, it is noted as per MPEP 2145:
One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to be an argument that attacks the reference(s) individually. Where an applicant’s reply establishes that each of the applied references fails to teach a limitation and addresses the combined teachings and/or suggestions of the applied prior art, the reply as a whole does not attack the references individually as the phrase is used in Keller and reliance on Keller would not be appropriate. This is because “[T]he test for obviousness is what the combined teachings of the references would have suggested to [a PHOSITA].” In re Mouttet, 686 F.3d 1322, 1333, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012).
Applicant first argues that Jenkins does not disclose a “polymer matrix” as in the instant claims:
The Jenkins Publication does not disclose a polymer matrix in particle form combined with particles of tadalafil to form a subcutaneous implant. Rather in the Jenkins Publication there is no matrix, there is only a polymer used to make a surface stabilizer on the nanoparticles of the tadalafil.
As to the meaning of the term “polymer matrix” in the instant product claims, the Specification provides the following:
[0031] The proposed bioabsorbable implant may have in its constitution only tadalafil but is preferably formed by tadalafil particles dispersed homogeneously in a bio erodible and bioabsorbable polymer matrix. Such a polymer matrix may be formed of a polymer or a mixture of polymers.
…
[0035] The implant manufacturing process starts with the addition of 25 to 250 mg of tadalafil in the polymer matrix chosen in the proportion of 1 to 20% in relation to the weight of the drug, in its dry forms, in powder. The mixture is then added into a container to be homogenized. If the polymer solvent is not also tadalafil solvent, it will be dispersed in the form of particles or suspension, and a mixer can be used to make the solution homogeneous. Then, this solution is dried and later molded to the shape of the implant (1) or other desired shape.
Thus, the claim is construed as a physical combination of tadalafil particles dispersed or homogenously combined with a polymer.
Jenkins teaches an equivalent process as described in the instant specification, specifically, through “homogenization” of the tadalafil with a polymer such as hydroxypropyl cellulose:
[0078] The invention provides compositions comprising PDE5 inhibitors, such as tadalafil particles and at least one surface stabilizer. The surface stabilizers preferably are adsorbed on, or associated with, the surface of the tadalafil particles. In some embodiments, surface stabilizers preferably physically adhere on, or associate with, the surface of the nanoparticulate tadalafil particles
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[0085] Representative examples of surface stabilizers include hydroxypropyl methylcellulose (now known as hypromellose), hydroxypropylcellulose, polyvinylpyrrolidone,
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[0138] The nanoparticulate PDE5 inhibitor compositions, such as nanoparticulate tadalafil compositions, can be made using, for example, milling, homogenization, precipitation, freezing, supercritical particle generation, or template emulsion techniques.
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[0145] Homogenization to Obtain Nanoparticulate Tadalafil Compositions
… the tadalafil particles can be contacted with one or more surface stabilizers either before or after attrition.
Thus, Jenkins does teach an equivalent polymer matrix as per the instant claims. Regarding the form of an implant, Jenkins specifically teaches administration of the composition by subcutaneous means ([0161]) which is also the same as the instant claims (claim 1 “A long-lasting reabsorbable subcutaneous implant …”). Furthermore, one of ordinary skill in the art following the teaching of Jenkins would have considered dispersing tadalafil homogenously in a polymer matrix and arrived at the claimed invention with a reasonable expectation of success because such a technique was well-known in the art and specifically suggested by Jenkins. Jenkins also teaches processing of the composition including compressing ([0113]) and sterilization ([0157]) which one of ordinary skill in the art would have considered routine in pharmaceutical formulation.
Applicant next argues that Melder teaches a different drug load and a different use/route of administration and therefore not analogous prior art. This argument is not persuasive because both Jenkins and Melder are in the field of administration of PD-5 inhibitors, including specifically tadalafil, for treating erectile dysfunction in men. Thus, the prior art highly analogous and are in the same field of endeavor and properly considered in the obviousness rejection. One of ordinary skill in the art would combine their knowledge and experience in pharmaceutical formulation and delivery and combine the teachings in a manner that renders the claims obvious, including in the use of well-known polymers such as “poly(D,L-lactic acid)” also known as “poly(racemic lactic acid)” (as per instant claim 2) as disclosed by Melder ([0042]).
Applicant argues that Melder does not disclose the particular sizes and shapes as per the claims. This argument is not persuasive because one of ordinary skill in the art would reasonably consider various shapes including cylindrical rod shapes of various lengths would could be utilized as an implant and optimize among the mm scale and arrive at the claimed invention with a reasonable expectation of success. MPEP 2144.04: In re Dailey, 357 F.2d 669, 149 USPQ 47 (CCPA 1966) (The court held that the configuration of the claimed disposable plastic nursing container was a matter of choice which a person of ordinary skill in the art would have found obvious absent persuasive evidence that the particular configuration of the claimed container was significant.).
Applicant next argues that Fritz does not disclose the particular sizes, shape and ratios claimed. This argument is not persuasive because Fritz teaches non-degradable polymers selected from acrylates to retain mechanical stability of the implant ([0079]: “methyl methacrylate (MMA) … . Most preferred is MMA. The polymer should be present in the core in a hydrated or partially hydrated (hydrogel) form. Such polymers are preferably cross-linked in order to provide suitable hydrogel properties and structure, such as enhanced non-biodegradability, and to help retain the mechanical stability of the polymer structure by resisting dissolution by water.”). Such a formulation would have been an obvious variation as suggested by the combination of prior art including among dimensions suitable for use as an implant of 0.2 to 1mm. Furthermore, one of ordinary skill in the art following the combined teaching of the prior art would have considered forming a subcutaneous implant device as claimed routine and withing their technical grasp.
Regarding the amendments altering the scope of the material in claims 2 and 7, Jenkins teaches polymethylmethacrylate ([0086], claim 10); Melder teaches “poly(D,L-lactic acid)” also known as “poly(racemic lactic acid)” ([0042]). Thus, one of ordinary skill in the art would have considered utilizing the same ingredient in the same manner and arrive at the claimed invention with a reasonable expectation of success.
Conclusion
No claims 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626