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 .
Priority
This application is a divisional of Application No. 17/899561 (filed on 8/30/2022), which in turn is a divisional of Application No. 15/917742 (filed on 3/11/2018), which claims priority benefit of U.S. Provisional Application No. 62/470250 (filed on 3/11/2017) under 35 U.S.C. 119(e).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/19/2024 does not comply with 37 CFR 1.98(a)(3)(i) since it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. Accordingly, some of the references have not been considered as indicated by a strike-through.
Drawings
The drawings are objected to because Figure 4 (text in the table) and Figure 5 (x- and y-axis labels, symbols) are too small to read. 37 C.F.R. 1.84 section (p)(3) requires that “Numbers, letters, and reference characters must measure at least .32 cm. (1/8 inch) in height”, while section (l) states “All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined”. See MPEP § 608.02(V).
In addition to Replacement Sheets containing the corrected drawing figure(s), applicant is required to submit a marked-up copy of each Replacement Sheet including annotations indicating the changes made to the previous version. The marked-up copy must be clearly labeled as “Annotated Sheets” and must be presented in the amendment or remarks section that explains the change(s) to the drawings. See 37 CFR 1.121(d)(1). Failure to timely submit the proposed drawing and marked-up copy will result in the abandonment of the application.
Claim Objections
Claim 50 is objected to because of the following informality: unnecessary conjunction (“and”) at the end of line 2. Appropriate correction is required.
Claim 65 is objected to because PLG is the same polymer as PLGA. Both PLG and PLGA refer to poly(lactide-co-glycolide). If applicant meant to recite polyglycolic acid, the correct abbreviation is “PGA”.
Claims 65-66 are also objected to since abbreviations (“PLA, PLG, PLGA” and “PEG”) are used without providing the full form. Any abbreviation should be defined when first recited in a set of claims by spelling out the full term followed by the abbreviation in parentheses. To resolve this issue and the one identified in the previous paragraph, “PLA, PLG, PLGA” in claim 65 should be amended to “polylactide (PLA), polyglycolide (PGA), poly(lactide-co-glycolide) (PLGA)” and “PEG” in claim 66 should be amended to “polyethylene glycol (PEG)”.
Claim 70 is objected to due to lack of space between the number and unit in “120nm”. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 50-66, 70, 81, and 83 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature and natural phenomenon without significantly more.
The United States Patent and Trademark Office (USPTO) issued a revised guidance for evaluating subject matter eligibility, referred to as “2019 Revised Patent Subject Matter Eligibility Guidance”, which became effective on January 7, 2019 (see 84 Fed. Reg. 50) and updated on October 2019 and July 2024. In the instant application, the claims recite a law of nature and natural phenomenon. This judicial exception is not integrated into a practical application, and the claims do not include additional elements that are sufficient to amount to significantly more than said judicial exception as explained below:
Subject Matter Eligibility Guidance
A three-step inquiry has been established to determine subject matter eligibility under 35 U.S.C. 101, in accordance with MPEP 2106:
Step (1). Is the claim directed to a process, machine, manufacture, or composition of matter?
Step (2A). Is the claim directed to a law of nature, natural phenomenon (product of nature), or an abstract idea?
Prong 1 – Does the claim recite a law of nature, natural phenomenon, or an abstract idea?
Prong 2 – If the claim recites a judicial exception, does it recite additional elements that integrate the judicial exception into a practical application? Limitations that are indicative of integration into a practical application include:
Improvements to the functioning of a computer, or to any other technology or technical field. See MPEP 2106.05(a)
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. See Vanda Memo
Applying the judicial exception with, or by use of, a particular machine. See MPEP 2106.05(b)
Effecting a transformation or reduction of a particular article to a different state or thing. See MPEP 2106.05(c)
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. See MPEP 2106.05(e) and Vanda Memo.
Step (2B). If the recited judicial exception is not integrated into a practical application, does the claim recite additional elements that amount to significantly different than the judicial exception such that they provide an inventive concept? This step includes evaluation of the same considerations under Step (2A), Prong 2, as well as two additional considerations:
Adding a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; and
Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present.
Analysis in View of the Interim Guidance
The answer to Step (1) is “yes” since the claims are directed to a composition of matter, which is a statutory category.
The answer to Step (2A) is “yes” because the claimed composition is directed to a law of nature and natural phenomenon, specifically natural products.
Prong 1: Claim 50 recites “immunosuppressant”, “uricase”, and “anti-inflammatory therapeutic” as components of the claimed composition. These components encompass products of nature:
1) immunosuppressants include natural mTOR inhibitors like rapamycin and curcumin (but since the immunosuppressant is specified to be contained in “synthetic nanocarriers”, the first component as a whole is not considered a natural product);
2) uricase is an enzyme found nature like in bacteria, fungi, and mammals; and
3) anti-inflammatory therapeutics include natural compounds like colchicine.
Claim 53 additionally requires one or more compositions comprising an infusion reaction therapeutic, which includes natural antihistamines such as quercetin. Thus, the claimed composition is directed to a mixture of a non-natural product (first component) and natural products (second and third components).
MPEP § 2106.04(c)(I)(A) states that “Where the claim is to a nature-based product in combination with non-nature based elements (e.g., a claim to "a yogurt starter kit comprising Lactobacillus in a container with instructions for culturing Lactobacillus with milk to produce yogurt"), the markedly different characteristics analysis should be applied only to the nature-based product limitation. For instance, for the yogurt starter kit example, the Lactobacillus would be analyzed for markedly different characteristics. The container and instructions would not be subject to the markedly different characteristics analysis as they are not nature-based products, but would be evaluated as additional elements in Prong Two…”. So in this case, the markedly different characteristics analysis is only applied to the second and third components.
The recited naturally occurring components are not found together in nature. However, there is no evidence demonstrating that the claimed composition is markedly different from its closest natural counterpart (ex. the combined effect of the various components is greater than the sum of the individual effects). Applicant’s working examples show that only the first two recited components were combined and evaluated, i.e., the anti-inflammatory therapeutic is not provided together with the immunosuppressant and uricase in tested compositions. Furthermore, only one form of uricase (pegylated recombinant uricase from yeast) and one type of immunosuppressant-containing nanocarriers (rapamycin-containing nanocarriers) were assessed. As such, results cannot be extended to all other immunosuppressants in nanocarriers and other types of uricase. So given that the various components are broadly recited (not limited to specific immunosuppressant-containing nanocarriers, uricase, and anti-inflammatory therapeutic), any showing of a markedly different characteristic would be deemed not commensurate in scope with the full scope of the claims.
Prong 2: The presence of “synthetic nanocarriers” containing the immunosuppressant does not limit the claimed composition to a particular treatment/prophylaxis of a disease or disorder, nor meaningfully ties them to a certain field of use. It does not cause a transformation or reduction of the claimed composition. Thus, this additional element does not integrate the recited judicial exception into a practical application. Further defining the type of polymer that comprise said nanocarriers, as well as specifying their diameter size and immunosuppressant load as required in some dependent claims, also do not integrate the recited natural products into a practical application.
The answer to Step (2B) is “no”. Combining a composition comprising an uricase with a composition comprising synthetic nanocarriers comprising an immunosuppressant is known in the art. For example, Kishimoto et al. discloses synthetic vaccine particles carrying rapamycin and pegylated uricase (Abstract, page 890; Figure 1A, page 891). Although Kishimoto et al. does not teach a composition comprising an anti-inflammatory therapeutic, Reinders et al. (Therapeutics and Clinical Risk Management 2010, Vol. 6, pages 543-550) acknowledges that patients receiving pegylated uricase treatments experience infusion reactions (IR) and gout flares. Referring to a clinical study by Sundy et al. (Journal of American Medical Association 2011, Vol. 306, pages 711-720), glucocorticosteroids such as colchicine or nonsteroidal anti-inflammatory drugs (NSAIDs) are disclosed to be useful for preventing antibody formation that result in IR and preventing gout flares (Abstract, page 543). Based on the teachings of Reinders et al. and Sundy et al., it would have been obvious to combine Kishimoto et al.’s composition with colchicine/NSAID with reasonable expectation that such combination would help block gout flares and IR.
Hence, the claims are not patent subject matter eligible.
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.
Claims 50-66 are rejected under 35 U.S.C. 103 as being unpatentable over Kishimoto et al. (Nature Nanotechnology 2016, Vol. 11, pages 890-899) in view of Reinders et al. (Therapeutics and Clinical Risk Management 2010, Vol. 6, pages 543-550) and Kent et al. (Pub. No. WO 2018/089808 A1).
Kishimoto et al. provides synthetic vaccine particles containing rapamycin (SVP-rapamycin) that are co-administered with pegsiticase to uricase-deficient mice having elevated levels of serum uric acid. The synthetic particles are nanocarriers comprising PLA/PLA-PEG (Abstract; Figure 1A, page 891).
The combination of SVP-rapamycin and pegsiticase was found to inhibit the formation of antidrug antibodies (ADA), which is a common cause for adverse hypersensitivity reactions and failure of biotherapeutic treatments, whereas pegsiticase alone did not reduce uric acid levels when administered as repeated injections. These results indicate development of an anti-uricase IgG response that allows maintenance of low serum uric acid levels. Similar results were obtained with cynomolgus monkeys (left column, page 895; Figure 5, page 896). Hence, biologic therapies with tolerogenic nanoparticles offer a promising approach to minimize ADA formation that is associated with adverse hypersensitivity reactions and loss of efficacy (Conclusion, left column, page 898).
Kishimoto et al. is comparable to the instant application’s composition as explained below:
Regarding claim 50: the SVP-rapamycin (a synthetic nanocarrier comprising the immunosuppressant rapamycin) and pegsiticase (a PEGylated uricase also known as pegadricase) corresponds to “A composition, comprising: 1) a composition comprising synthetic nanocarriers comprising an immunosuppressant; and 2) a composition comprising an uricase”.
What differentiates Kishimoto et al. from the claimed composition is that it does not teach combining SVP-rapamycin and pegsiticase with “3) a composition comprising an anti-inflammatory therapeutic”.
Treatment with pegylated uricase, however, is known to cause infusion reactions (IR) and gout flares as substantiated by Reinders et al. (Abstract, page 543). According to Reinders et al., majority of patients treated with pegloticase every 2 or 4 weeks in Phase II clinical trials developed antibodies to pegloticase, which appear to be associated with infusion reactions (IR) (first par. in right col., page 546). In Phase III clinical trials, glucocorticosteroids were utilized to reduce antibody formation and gout flares. Patients treated with pegloticase were also administered with colchicine (which is a nonsteroidal anti-inflammatory drug or NSAID) as gout prophylaxis, as well as fexofenadine, acetaminophen, and hydrocortisone as IR prophylaxis (last par. in right column, page 546). Results demonstrate that the incidence and frequency of gout flare significantly decreased during months 4-6 in subjects treated every 2 weeks of pegylated uricase (first par. in left column, page 547). Hence, Reinders et al. recommends having an anti-inflammatory or anti-immunologic strategy to prevent anti-pegloticase antibody formation and gout flares induced by urate mobilization (second par. in right col. page 548).
Reinders et al. is further supported by Kent et al., which teaches combining a steroid with uricase for reducing an infusion reaction or antibody response to uricase treatment (lines 13-14, page 1; lines 2-7, page 2; lines 2-3, page 33). The uricase can be a pegylated uricase like pegloticase (lines 21-22, page 5; lines 2-4, page 26), while applicable steroids include hydrocortisone, methylprednisolone, and prednisone that can be administered concurrently with the uricase (lines 2-7, page 7). Kent et al. also teaches administering prior to or concurrently an anti-inflammatory drug like colchicine (lines 10-13, page 6).
Based on the teachings of Reinders et al. and Kent et al., a person with ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to combine a NSAID like colchicine with SVP-rapamycin and pegsiticase, as well as add an IR prophylaxis like fexofenadine, paracetamol, and hydrocortisone. The resulting/modiifed composition is expected to provide the benefit of inhibiting the formation of anti-pegloticase antibodies and decrease the occurrence of gout flares. The rationale supporting obviousness is that some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP § 2143.01 and KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385, 1395-97 (2007).
Thus, claim 50 is obvious over Kishimoto et al. in view of Reinders et al. and Kent et al..
Regarding claim 51: the colchicine in the resulting/modified composition meets the limitation “wherein the anti-inflammatory therapeutic is a non-steroidal anti-inflammatory drug (NSAID)”.
Regarding claim 52: colchicine is identical to “wherein the anti-inflammatory therapeutic is colchicine…”.
Regarding claim 53: the fexofenadine, paracetamol, and hydrocortisone serve as IR prophylaxis, thereby satisfying “wherein the composition further comprises one or more compositions comprising an infusion reaction therapeutic”.
Regarding claim 54: fexofenadine is an antihistamine while hydrocortisone is a corticosteroid, which fulfill “wherein the one or more compositions comprising an infusion reaction therapeutic comprises an antihistamine and/or a corticosteroid”.
Regarding claim 55: fexofenadine is the same as “wherein the antihistamine is fexofenadine”.
Regarding claim 56: the hydrocortisone is not identical to “wherein the corticosteroid is methylprednisolone, prednisone or dexamethasone”.
Nevertheless, hydrocortisone is a corticosteroid like methylprednisolone, prednisone, and dexamethasone. As discussed above, Kent et al. teaches that the steroid that can be combined with uricase includes corticosteroids such as hydrocortisone, methylprednisolone, and prednisone, indicating that the latter two substances are known alternatives to hydrocortisone. It would have thus been obvious to replace the hydrocortisone in the resulting/modified composition with methylprednisolone or prednisone and predict that either one would still prevent IR. Simple substitution of one known element for another obtains nothing more than predictable results.
Regarding claim 57: pegsiticase is a pegylated uricase and therefore equivalent to “wherein the uricase is pegylated uricase”.
Regarding claim 58: pegisticase is also referred to as pegadricase, thus meeting “wherein the pegylated uricase is pegadricase or pegloticase”.
Regarding claim 59: rapamycin is an mTOR inhibitor and satisfies “wherein the immunosuppressant is a mammalian target of rapamycin (mTOR) inhibitor”.
Regarding claim 60: rapamycin is not the same as “wherein the mTOR inhibitor is a rapalog”. Despite this, it is known in the art that rapalogs are rapamycin analogs that share the same core molecular structure as rapamycin. One with ordinary skill in the art would have expected that substituting the rapamycin with rapalog would yield similar results as it would also inhibit the mTOR pathway and consequently help inhibit inflammation.
Regarding claim 61: the rapamycin in SVP-rapamycin is identical to “wherein the mTOR inhibitor is rapamycin”.
Regarding claim 62: the rapamycin being contained inside SVP, which are synthetic nanocarriers, fulfill “wherein the immunosuppressant is encapsulated in the synthetic nanocarriers”.
Regarding claim 63: the SVP is made of polymers PLA/PLA-PEG and therefore meets “wherein the synthetic nanocarriers are polymeric synthetic nanocarriers”.
Regarding claim 64: PLA is a hydrophobic polyester, thus satisfying “wherein the polymeric synthetic nanocarriers comprise a hydrophobic polyester”.
Regarding claim 65: the SVP comprising PLA/PLA-PEG reads on “wherein the hydrophobic polyester comprises PLA, PLG, PLGA or polycaprolactone”.
Regarding claim 66: PLA-PEG fulfills “wherein the polymeric synthetic nanocarriers further comprise PEG”.
Claims 50-66, 70, 81, and 83 are rejected under 35 U.S.C. 103 as being unpatentable over Kishimoto et al. (Nature Nanotechnology 2016, Vol. 11, pages 890-899) in view of Reinders et al. (Therapeutics and Clinical Risk Management 2010, Vol. 6, pages 543-550), Kent et al. (Pub. No. WO 2018/089808 A1), and Kishimoto et al. II (Pub. No. US 2014/0328924 A1).
The teachings of Kishimoto et al., Reinders et al., and Kent et al. are set forth above and applied herein. These prior art are found to render claims 50-66 obvious.
The resulting/modified composition of Kishimoto et al., Reinders et al., and Kent et al. is similar to the following claims:
Regarding claim 70: Kishimoto et al. does not disclose the diameter of the SVP containing the rapamycin and therefore does not teach “wherein the mean of a particle size distribution obtained using dynamic light scattering of the synthetic nanocarriers is a diameter greater than 120nm”.
Kishimoto et al. II, however, shows how to prepare synthetic carriers comprising an immunosuppressant including mTOR inhibitors such as rapamycin or rapamycin analog (par. [0009]-[0011], [0055]). The synthetic nanocarriers can be made via a nanoprecipitation process or spray drying under conditions that produce particles of a desired size or property (par. [0168-[0169]). In Example 1, rapamycin-containing nanocarriers were prepared by mixing a solution of PLGA, PLA-PEG-OMe, and rapamycin with a solution of polyvinyl alcohol to yield an oil-in-water emulsion prior to adding phosphate buffer and stirring at room temperature for 2 hours to allow dichloromethane to evaporate and nanocarriers to form (par. [0180]-[0184]). Subjecting the formed nanocarriers to dynamic light scattering showed that their diameter is 218 nm (par. [0185]). One with ordinary skill in the art would have further altered the resulting/modified composition by preparing the SVP-rapamycin as taught by Kishimoto et al. II with reasonable expectation that it would have a diameter of 218 nm. Combining prior art elements according to known methods yields predictable results. See MPEP § 2143 and KSR, 550 U.S. 398, 82 USPQ2d at 1395.
Thus, claim 70 is obvious over Kishimoto et al. in view of Reinders et al., Kent et al., and Kishimoto et al. II.
Regarding claims 81 and 83: Kishimoto et al. also does not disclose the amount of rapamycin in the nanocarriers and therefore does not teach the limitations “wherein the load of the immunosuppressant of the synthetic nanocarriers is 7-12% or 8-12% by weight” and “wherein the load of the immunosuppressant of the synthetic nanocarriers is 7%, 8%, 9%, 10%, 11%, or 12% by weight”.
Nonetheless, Kishimoto et al. II’s method of preparing immunosuppressant-containing synthetic carriers entails loading the immunosuppressant in the synthetic nanocarriers at an amount of between 0.0001% wt. and 50% wt. such as 0.1-10% wt. (par. 0012]). In the working example described above (Example 1), the produced rapamycin-containing nanocarriers have a rapamycin load of 9.9% wt (par. [0185]). Accordingly, preparing the SVP-rapamycin in accordance with Kishimoto et al. II’s method is expected to generate nanocarriers having a rapamycin load that reads on the specified load of the immunosuppressant.
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 50-63 and 70 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of prior U.S. Patent No. 10,668,053 in view of Reinders et al. (Therapeutics and Clinical Risk Management 2010, Vol. 6, pages 543-550); as well as claims 64-66, 81, and 83 over U.S. Patent No. 10,668,053 in view of Kishimoto et al. II (Pub. No. US 2014/0328924 A1).
U.S. patent 10,668,053 discloses a method for reducing or preventing an anaphylactic reaction to a non-allergenic antigen. The method comprises: providing the non-allergenic antigen, the non-allergenic antigen being unattached to synthetic nanocarriers; providing a composition comprising synthetic nanocarriers attached to an mTOR inhibitor; and administering to a subject having or at risk of having an anaphylactic reaction to a non-allergenic antigen the composition concomitantly with the non-allergenic antigen prior to subsequent administration of the non-allergenic antigen without administration of the composition. In some embodiments, the synthetic nanocarriers can comprise polymeric nanoparticles and have a diameter greater than 100 nm.
The claims at issue are not identical but they are not patentably distinct from each other because the composition comprising synthetic nanocarriers attached to an mTOR inhibitor are required to be administered concomitantly with the non-allergenic antigen, which can comprise a therapeutic macromolecule like pegsiticase. One with ordinary skill in the art before the effective filing date of the claimed invention would have thus combined them as a single formulation.
The U.S. patent’s method does not comprise further administering an anti-inflammatory therapeutic.
Regardless, Reinders et al. teaches that anti-inflammatory agents and glucocorticosteroids are useful for preventing gout flares and IR. It would have also been obvious to include an NSAID like colchicine as gout prophylaxis, as well as fexofenadine, paracetamol, and hydrocortisone as IR prophylaxis. Such addition would help inhibit gout flares and IR on a patient treated with a therapeutic macromolecule like pegsiticase given that pegsiticase treatment is known to cause infusion reactions and the U.S. patent aims to reduce or prevent an anaphylactic reaction to the non-allergenic antigen. Modifying or combining the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so is the rationale supporting obviousness.
In some dependent claims of the instant application, the type of material that make up the synthetic nanocarriers and the amount of rapamycin in said nanocarriers are specified, both of which are not disclosed by the U.S. patent.
Kishimoto et al. II provides synthetic carriers comprising an immunosuppressant including mTOR inhibitors such as rapamycin, and a method of preparing them (par. [0009]-[0011], [0055]). For example, rapamycin-containing nanocarriers can be prepared by mixing a solution of PLGA, PLA-PEG-OMe, and rapamycin with a solution of polyvinyl alcohol to yield an oil-in-water emulsion before adding phosphate buffer and stirring the resulting mixture at room temperature for 2 hours to allow production of nanocarriers containing 9.9% wt. of rapamycin (par. [0180]-[0185]). A person with ordinary skill in the art would have further altered the single formulation by preparing the synthetic nanocarriers using PLGA, PLA-PEG-OMe, and rapamycin as taught by Kishimoto et al. II and predict that it would yield PLGA/PLA-PEG nanocarriers containing 9.9% wt. rapamycin. Combining prior art elements according to known methods yields predictable results. See MPEP § 2143 and KSR, 550 U.S. 398, 82 USPQ2d at 1395.
Claims 50-65 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,194,078; as well as claims 66, 70, 81, and 83 over U.S. Patent No. 12,194,078 in view of Kishimoto et al. II (Pub. No. US 2014/0328924 A1).
The U.S. patent is drawn to a method comprising: concomitantly administering to a subject in need thereof 1) a composition comprising synthetic nanocarriers comprising an immunosuppressant and 2) a composition comprising an uricase; and further comprising administering 3) a composition comprising an anti-inflammatory therapeutic. In some aspects, the anti-inflammatory therapeutic can be a NSAID such as colchicine or ibuprofen. An embodiment limits the uricase to a pegylated uricase like pegadricase or pegloticase. In another embodiment, the immunosuppressant is an mTOR inhibitor including rapamycin and a rapalog.
Although the claims at issue are not identical, they are not patentably distinct from each other because the composition comprising an anti-inflammatory therapeutic is administered concomitantly with the composition comprising synthetic nanocarriers comprising an immunosuppressant and the composition comprising an uricase. It would have therefore been obvious for a person with ordinary skill in the art before the effective filing date of the claimed invention to combine the three compositions together as a single formulation. And since the U.S. patent teaches further administering to the subject one or more compositions comprising an infusion reaction therapeutic comprising an antihistamine like fexofenadine and/or a corticosteroid such as methylprednisolone, prednisone or dexamethasone, it would have also been obvious to incorporate said substances to the single formulation.
The U.S. patent also differs from the claimed invention in that it does not disclose the material comprising the synthetic nanocarriers, the diameter of the synthetic nanocarriers, and the amount of rapamycin in the synthetic nanocarriers.
But as discussed above, Kishimoto et al. II teaches a method of preparing synthetic carriers comprising an immunosuppressant like rapamycin (par. [0009]-[0011], [0055]). A working example shows mixing a solution of PLGA, PLA-PEG-OMe, and rapamycin with a solution of polyvinyl alcohol, adding phosphate buffer, and stirring the resulting mixture at room temperature for 2 hours to evaporate dichloromethane and form nanocarriers (par. [0180]-[0184]). The formed nanocarriers were found to have a diameter of 218 nm and a rapamycin load of 9.9% wt. (par. [0185]). A person with ordinary skill in the art before the effective filing date of the claimed invention would have further altered the single formulation by preparing the synthetic nanocarriers using PLGA, PLA-PEG-OMe, and rapamycin as taught by Kishimoto et al. II with reasonable expectation that rapamycin-containing PLGA/PLA-PEG nanocarriers having a diameter of 218 nm and rapamycin load of 9.9% wt. would be produced. Combining prior art elements according to known methods yields predictable results. See MPEP § 2143 and KSR, 550 U.S. 398, 82 USPQ2d at 1395.
Claims 50-66, 70, 81, and 83 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 116-135 of co-pending Application No. 18/818714 in view of Reinders et al. (Therapeutics and Clinical Risk Management 2010, Vol. 6, pages 543-550).
The co-pending application is directed to a method of treating a subject with an elevated serum uric acid level and/or undesired uric acid deposits or identified as having had or as being expected to have gout flare. The treatment method involves administering to said subject (i) a composition comprising rapamycin and synthetic nanocarriers comprising PLA and PLA-PEG and (ii) a composition comprising pegsiticase. One embodiment of the synthetic carriers is that they have a diameter greater than 120 nm, greater than 150 nm, greater than 200 nm, or greater than 250 nm. In another embodiment, the load of the rapamycin of the synthetic nanocarriers is 7-12%, 8-12%, 7-10%, or 8-10% by weight.
The co-pending application is different from the claimed invention in that it does not teach that the two compositions are combined together with an anti-inflammatory therapeutic.
However, the disclosed treatment method specifies concomitantly administering the two recited compositions so it would be obvious for one with ordinary skill in the art to combine them as one composition. Furthermore, Reinders et al. teaches that anti-inflammatory agents and glucocorticosteroids facilitate prevention of gout flares and IR. Suitable NSAID includes colchicine while applicable glucocorticoids are fexofenadine, acetaminophen, and hydrocortisone. Thus, it would have been obvious to also incorporate an NSAID like colchicine to prevent gout, as well as fexofenadine, paracetamol, and hydrocortisone to prevent IRs. Obviousness is established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651
