DETAILED ACTION
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 .
Status of the Claims
Claims 1-10 are pending and under current examination.
Information Disclosure Statement
Non-patent literature citations provided without required information (journal title, volume, issue number if relevant, page numbers) were not considered by the examiner as indicated by a line through on the IDS. See MPEP 609.04(a):
37 CFR 1.98(b) requires that each item of information in an IDS be identified properly. U.S. patents must be identified by the inventor, patent number, and issue date. U.S. patent application publications must be identified by the applicant, patent application publication number, and publication date. U.S. applications must be identified by the inventor, the eight digit application number (the two digit series code and the six digit serial number), and the filing date. If a U.S. application being listed in an IDS has been issued as a patent or has been published, the applicant should list the patent or application publication in the IDS instead of the application. Each foreign patent or published foreign patent application must be identified by the country or patent office which issued the patent or published the application, an appropriate document number, and the publication date indicated on the patent or published application. Each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue. The place of publication refers to the name of the journal, magazine, or other publication in which the information being submitted was published. See MPEP § 707.05(e), for more information on data that should be used when citing publications and electronic documents. Pending U.S. applications that are being cited can be listed under the non-patent literature section or in a new section appropriately labeled.
Drawings
The drawings are objected to because the figures contain text that is not in English. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 1, 5, and 7 are objected to because of the following informalities:
Claim 1 recites “a proportional amount … are”. This is ungrammatical because the noun and verb do not agree in number. Amending to recite “a proportional amount … is” would be remedial.
The word “triodothyronine” in claim 5, line 20 appears to be a typographical error for triiodothyronine.
The word “triiodothyronine” is repeated in claim 5, lines 20-21. Was “triiodothyronine sulfate” intended in one instance?
Claim 7 recites “…said isolated triiodothyronine, said isolated triiodothyronine sulfate, and said thyroxine are mixed with a material selected for said polymeric matrix, and is subsequently dried…” This language is ungrammatical because the noun and verb do not agree in number. Amending the claim to replace the word “is” with “are” would be remedial.
Appropriate correction is required.
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.
Claims 1-10 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.
The term “long-lasting” in each of claims 1-10 is a relative term which renders the claim indefinite. The term “long-lasting” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As such, the stability of the claimed implant is indefinite.
The term “isolated” in claim 1, lines 9, 11, and 13 renders the claim indefinite because it implies a limit on what substances also may be present in the composition or may be present in some unspecified proximity to the pharmacologically active substances, without identifying what those substances are.
The term “a proportional amount” in each of claims 1, 5, and 10 is a relative term which renders the claim indefinite. The term “a proportional amount” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Therefore it is unclear what the proportion is to and, since a proportion necessarily refers to an amount of one element relative to another, what quantities or elements are thereby be limited by the proportion.
The term “isolated” in claim 5, lines 11, 13, 15, and 20-21 and renders the claim indefinite because it implies a limit on what substances also may be present in the composition or may be present in some unspecified proximity to the pharmacologically active substances, without identifying what those substances are.
The term “isolated” in claim 7, lines 5, 6, and 7 renders the claim indefinite because it implies a limit on what substances also may be present in the composition or may be present in some unspecified proximity to the pharmacologically active substances, without identifying what those substances are.
Each of claims 7-9 are directed to a product, an implant, but claim 7 recites “…are mixed with a material…”; claim 8 recites “…are mixed as powders…” and claim 9 recites “…are molded into a form and sterilized…” implying method steps for using this product in each instance. Per MPEP 2173.05(p), a single claim which claims both an apparatus and the method steps of using the apparatus is indefinite.
See In re Katz Interactive Call Processing Patent Litigation, 639 F.3d 1303 (Fed. Cir. 2011). In Katz, a claim directed to “A system with an interface means for providing automated voice messages…to certain of said individual callers, wherein said certain of said individual callers digitally enter data” was determined to be indefinite because the italicized claim limitation is not directed to the system, but rather to actions of the individual callers, which creates confusion as to when direct infringement occurs. In re Katz, 639 F.3d at 1318 (citing IPXL Holdings v. Amazon.com, Inc., 430 F.2d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005), in which a system claim that recited “an input means” and required a user to use the input means was found to be indefinite because it was unclear “whether infringement … occurs when one creates a system that allows the user [to use the input means], or whether infringement occurs when the user actually uses the input means.”); < Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990) (claim directed to an automatic transmission workstand and the method of using it held ambiguous and properly rejected under 35 U.S.C. 112(b)).
In the interest of compact prosecution each of claims 7-9 are interpreted as reciting product by process language.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 7 recites the broad recitation “a material”, and the claim also recites “said polymer matrix” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 7 recites the limitation "is subsequently dried" in line 15. There is insufficient antecedent basis for this limitation in the claim. Specifically, for something to be dried, there must have been some liquid present; however, the product by process language in claim 7 does not indicate that a liquid had been present.
The term “isolated” in claim 8, lines 4-5 renders the claim indefinite because it implies a limit on what substances also may be present in the composition or may be present in some unspecified proximity to the pharmacologically active substances, without identifying what those substances are.
The term “isolated” in claim 9, lines 13 and 14 renders the claim indefinite because it implies a limit on what substances also may be present in the composition or may be present in some unspecified proximity to the pharmacologically active substances, without identifying what those substances are.
The term “isolated” in claim 10, lines 7-11 renders the claim indefinite because it implies a limit on what substances also may be present in the composition or may be present in some unspecified proximity to the pharmacologically active substances, without identifying what those substances are.
Claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness concerns outlined above.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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 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 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Patel et al. (WO2018067882; publication date: 04/12/20218) in view of Santini et al. (Endocr Pract. 2014 Jul;20(7):680-9; cited in the IDS filed 09/27/2023).
With regard to instant claims 1, 5, and 10, Patel discloses a subdermal (i.e. subcutaneous; 0137) implant for treating hypothyroidism (title, abstract, claim 66) containing a combination of the pharmacologically active substances thyroxine (T4) and triiodothyronine (T3) (0014) in a polymer core (i.e. matrix) surrounded by a polymer coating (abstract, 0014). The polymers that form the matrix and coating may be selected from a list that includes polymers that are bioerodable or non-bioerodable, and as such the implant may be resorbable (0026, 0104-0110). The implant provides drug release over a period of at least 30 days (0039), which the examiner considers to meet the criteria recited in the instant claims that the implant be long-lasting. With regard to the limitation recited in the instant claims that the triiodothyronine, triiodothyronine sulfate, and thyroxine be “isolated” and “pre-concentrated”, neither the claims nor the specification provides guidance as to the meaning of the words “isolated” or “pre-concentrated”. Patel discloses the drug substance to be incorporated with the polymer in the core as fine particles (i.e. dispersed as particles, as required by the instant claims; 0127), and thus the compounds are isolated from other active agents, they are not in solution, and they are isolated from their sources and concentrated relative to a drug in solution. For at least these reasons, the examiner considers Patel to disclose isolated, pre-concentrated drugs including triiodothyronine, and thyroxine. Patel teaches that the core pharmaceutical substance comprises about 1 wt% to about 80 wt% of the core (claim 26), therefore implicitly teaches a range in amount of polymer matrix that overlaps with the range recited in the instant claims. See MPEP 2144.05.
Patel does not disclose that the implant also contains triiodothyronine sulfate (T3S).
Santini teaches that after administration, T3S is absorbed following oral administration in hypothyroid humans; (2) after a single oral dose, T3S is converted to T3 [the active metabolite] in a dose-dependent manner, resulting in steady-state serum T3 concentrations for 48 hours (abstract).
It would have been prima facie obvious to also include T3S in addition to T3 and T4 in the implant taught by Patel. The artisan of ordinary skill would have been motivated to do so in order to provide an additional means to optimize sustained effective T3 plasma levels. The skilled artisan would have had reasonable expectation of success because Patel teaches that many other substances besides T3 and T4 can be included in the implant (0101, claim 27).
With regard to the amount of each of T3, T3S, and T4 required by the instant claims, Patel discloses a target plasma concentration for hypothyroidism (0132) and therefore it would have been merely optimization for one of ordinary skill to determine an optimal dose of each agent to achieve this target for a particular species or patient population. Please refer to MPEP 2144.05.
With regard to claims 2 and 6, the exemplary polymers for use in the core or the shell include poly(lactic acid), poly(glycolic acid), polyurethane, acrylate polymers, silicones etc. (see all polymers listed in para 0104 – 0110).
With regard to claim 3, the implant is a cylinder-shaped rod (0085, 0088) having dimensions of about 0.5 to about 7 mm in diameter (0085) This range overlap with the ranges required by the instant claims (see MPEP 2144.05). The range for length, 0.5 cm to 10 cm in length (0084), is longer than the range recited in the instant claims; however, Patel discloses further that a therapeutically effective amount can be administered to a patient as a single dose, or can be divided and administered as multiple doses (0074). It would have been prima facie obvious to shorten the length of the implant disclosed by Patel in order to obtain a dose required for a particular patient/condition, because Patel suggests doing so to achieve a “therapeutic amount” and as noted above, provides guidance as to target plasma concentrations of the active agents.
With regard to claim 4, as noted above, the implant is coated. The thickness of the coating, Patel teaches that in one embodiment, the core independently has a diameter between about 0.25 mm to about 6.75 mm and the shell independently has a thickness between about 0.125 mm to about 3.375 mm, with the proviso that the sum of the diameter of the core and twice the thickness of the shell is less than or equal to about 7 mm (that is, the total diameter of the implantable device is less than or equal to about 7 mm) (0086). Thus Patel discloses a range in coating thickness that overlaps with the range required by the instant claims, see MPEP 2144.05. The coating is on the core of the implant and therefore coats “at least some of the implant” as required by claim 4.
With regard to claims 7-9, which requires the pharmacologically active substances to be mixed with a material selected for said polymeric matrix and dried, this claim recites product by process language. According to MPEP 2113: product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. “The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art”. Thus, claim 7 is interpreted to read on particles of each a pharmacologically active substance distributed throughout a polymeric matrix; claim 8 only requires the pharmacologically active substances to have been mixed as powders at some point during manufacture and is therefore not considered particularly limiting of the final structure as other steps of e.g. dissolving the agents are not excluded by the claim; claim 9 reads on the implant according to claim 1 that is in “a form”. As the claim does not require the implant to remain sterile after the sterilization step, the examiner does not consider claim 9 to require that the implant be sterile. At para 0127, Patel discloses the following, relevant to instant claims 7-9: In some embodiments, the implantable devices of the invention can be produced by co-extruding the drug-containing core of the device and the porogen-containing shell. The drug substance is reduced to fine particles by milling (e.g., ball-milling, impact-milling), spray-drying, solvent precipitation, screening, or other method or combination of methods known in the art to produce fine particles. The drug can be combined with a polymer which is also prepared as fine particles to form the mixture used to make the drug-containing core [the active substance is mixed with a material selected for the polymer matrix]. Each blended mixture is heated to a temperature suitable for extrusion, such as the softening point of the polymer. At this point, optionally and if necessary, either or both of the softened mixtures can be homogenized. The mixtures are then co-extruded [i.e. the implant is formed from the blend of drug and polymer particles that had been mixed as powders]. The extruded implant can subsequently be sterilized (0128).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the 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 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over
claims 15-21 of copending Application No. 16985891;
claims 1, 2, and 4-8 of copending Application No. 18000117;
claims 1-7 of copending Application No. 18000127;
claims 1-7 of copending Application No. 18004057;
claims 1-9 of copending Application No. 18868715;
in view of Patel et al. (WO2018067882; publication date: 04/12/20218) in view of Santini et al. (Endocr Pract. 2014 Jul;20(7):680-9; cited in the IDS filed 09/27/2023).
The claims of the cited applications each embrace a long lasting resorbable, biodegradable or non-biodegradable implant for treating a disease comprising pharmacologically active substances containing a polymer matrix core coated with a polymer coating and containing the active substances dispersed through the matrix core formed from the same polymers required by the instant claims and providing extended release of the active substance.
The claims of the copending applications do not require triiodothyronine (T3), triiodothyronine sulfate (T3S), or thyroxine (T4).
Patel discloses implants having a polymer matrix core and a polymer coating (title, abstract) can be used to deliver many different active agents (0101, claim 27) including hypothyroidism. Santini teaches that after administration, T3S is absorbed following oral administration in hypothyroid humans; (2) after a single oral dose, T3S is converted to T3 [the active metabolite] in a dose-dependent manner, resulting in steady-state serum T3 concentrations for 48 hours (abstract).
It would have been prima facie obvious to deliver T3, T3S, and T4 with the implants of the copending applications. The skilled artisan would have been motivated to do so in order to provide a sustained treatment for hypothyroidism and had reasonable expectation of success because the prior art teaches such implants can be used to deliver various different drugs, including T3 and T4, specifically.
With regard to the limitation recited in the instant claims that the triiodothyronine, triiodothyronine sulfate, and thyroxine be “isolated” and “pre-concentrated”, neither the claims nor the specification provides guidance as to the meaning of the word “isolated” “pre-concentrated” in the instant claims. Patel discloses the drug substance to be incorporated with the polymer in the core as fine particles (i.e. dispersed as particles, as required by the instant claims; 0127), and thus the compounds are isolated from other active agents, they are not in solution, and they are isolated from their sources and concentrated relative to a drug in solution. For at least these reasons, the examiner considers Patel to disclose isolated, pre-concentrated drugs including triiodothyronine, and thyroxine. Patel teaches that the core pharmaceutical substance comprises about 1 wt% to about 80 wt% of the core (claim 26), therefore implicitly teaches a range in amount of polymer matrix that overlaps with the range recited in the instant claims. See MPEP 2144.05.
With regard to the amount of each of T3, T3S, and T4 required by the instant claims, Patel discloses an objective plasma concentration for hypothyroidism (0132) and therefore it would have been merely optimization for one of ordinary skill to determine an optimal dose of each agent to achieve this target for a particular species or patient population. Please refer to MPEP 2144.05.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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/KATHERINE PEEBLES/Primary Examiner, Art Unit 1617