Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on January 12, 2026 has been entered.
Claims 117, 119-126 and 128-132 are pending and being acted upon in this Office Action.
Priority
Applicant’ claim priority to provisional application 61/531,147 filed 09/06/2011, 61/531,153 filed 09/06/2011, 61/531,164 filed 09/06/2011, 61/531,168 filed 09/06/2011, 61/531,175 filed 09/06/2011, 61/531,180 filed 09/06/2011, 61/531,194 filed 09/06/2011, 61/531,204 filed 09/06/2011, 61/531,209 filed 09/06/2011, 61/531,215 filed 09/06/2011, 61/513,514 filed 07/29/2011 and 61/480,946 filed 04/29/2011, is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on January 12, 2026 has been considered by the examiner and an initialed copy of the IDS is included with this Office Action.
Claim objection
Claim 126 is objected to because of the following informality: “is a diameter is greater than 150 nm” should be “is a diameter greater than 150 nm”.
Rejection Withdrawn
The rejection of claim 119 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of the claim amendment.
Upon reconsideration in light of the amendment to claims 117 and 119 and Applicant’s arguments, see p. 6-10, the written description and enablement rejections of claims 117-126 and 128-132 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph are withdrawn.
The provisional rejection of claims 117-126 and 128-132 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 47 and 57-65 of copending Application No. 16/536,154 is withdrawn as the copending application has been abandoned.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 128 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Regarding claim 128, the metes and bounds of claim 128 render vague and indefinite because the claim depends from canceled claim 127. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention. See MPEP § 2173.05(d). MPEP § 608.01(n).
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 117, 119-126 and 128-132 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5-19 of U.S. Patent No. 10,420,835. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the issued patent (species) anticipate the claims under examination (genus).
10,420,835
18/177,714
A method comprising: (A) administering to a subject according to a protocol that was previously shown to reduce the number or activity of antigen-specific T effector cells in one or more test subjects: (i) a population of polymeric synthetic nanocarriers coupled to rapamycin, and (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen (species) that are not coupled to any synthetic nanocarriers; or
(B) reducing the number or activity of antigen-specific T effector cells in one or more test subjects by administering to the one or more test subjects: (i) a population of polymeric synthetic nanocarriers coupled to rapamycin, and (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen that are not coupled to any synthetic nanocarriers; or
(C) administering to a subject: (i) a population of polymeric synthetic nanocarriers coupled to rapamycin, and (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen that are not coupled to any synthetic nanocarriers; wherein the population of synthetic nanocarriers and MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen are in an amount effective to reduce the number or activity of antigen-specific T effector cells,
wherein at least 75% of the synthetic nanocarriers of the population of synthetic nanocarriers have a minimum dimension, obtained using dynamic light scattering, that is greater than 110 nm and a maximum dimension, obtained using dynamic light scattering, that is equal to or less than 500 nm, and wherein the load of the rapamycin on average across the population of synthetic nanocarriers is at least 2% but no more than 25% (weight/weight).
Administering a composition comprising the same therapeutic protein concomitantly with a composition comprising the same rapamycin coupled to polymeric nanocarrier is expected to reduce the generation of therapeutic protein specific undesired immune response.
117. (Currently Amended) a method for reducing the generation of an undesired immune response to a therapeutic protein in a subject comprising administering to the subject:
1) a composition comprising a population of polymeric synthetic nanocarriers that are coupled to rapamycin or a rapamycin analog, and
2) a composition comprising a therapeutic protein APC presentable antigen, which therapeutic protein APC presentable antigen comprises a therapeutic protein; wherein the load of the rapamycin or rapamycin analog on average across the population of polymeric synthetic nanocarriers is at least 2% but no more than 25% (weight/weight),wherein the polymeric synthetic nanocarriers have a minimum dimension, obtained using dynamic light scattering, that is greater than 110 nm, and a maximum dimension, obtained using dynamic light scattering, that is equal to or less than 500 nm, and wherein the composition of 1) and the composition of 2) are administered concomitantly and wherein the composition is in an amount effective to reduce the generation of an undesired immune response against the therapeutic protein.
118. (Currently Amended) The method of claim 117, wherein the therapeutic protein APC presentable antigen comprises a (i) MHC Class I-restricted and/or MHC Class II-restricted epitope(s) of the therapeutic protein and/or (ii) B cell epitope(s) of the therapeutic protein.
120. The method of claim 117, wherein the undesired immune response is the generation of therapeutic protein-specific antibodies and/or CD4+ T cell proliferation and/or activity and/or B cell proliferation and/or activity is reduced in the subject.
126. (Currently Amended) The method of claim 117, wherein the mean of a particle size distribution obtained using dynamic light scattering of the population of synthetic polymeric nanocarriers is a diameter is greater than 150 nm.
130. The method of claim 117, wherein the composition of 1) or 2) further comprises a pharmaceutically acceptable excipient.
2. The method of claim 1, wherein the method further comprises identifying the subject.
See Para. [0022].
3. The method of claim 1, wherein the antigen is a therapeutic protein (genus), an autoantigen or an allergen, or is associated with an inflammatory disease, an autoimmune disease, organ or tissue rejection or graft versus host disease.
119. (Currently Amended) The method of claim 117, wherein the therapeutic protein is an enzyme (species).
4. The method of claim 1, wherein the method further comprises assessing the number or activity of antigen-specific T effector cells in the subject prior to and/or after the administration.
132. The method of claim 117, wherein the composition of 2) is administered prior to or after the administration of the composition of 1).
5. The method of claim 1, wherein the subject has or is at risk of having an inflammatory disease, an autoimmune disease, an allergy, organ or tissue rejection or graft versus host disease.
6. The method of claim 1, wherein the subject has undergone transplantation.
7. The method of claim 1, wherein the subject has or is at risk of having an undesired immune response against a therapeutic protein that is being administered to the subject.
See para. [0116] to [0123]
8. The method of claim 1, wherein the administering is by intravenous, intraperitoneal, transmucosal, oral, subcutaneous, pulmonary, intranasal, intradermal or intramuscular administration.
131. The method of claim 117, wherein the composition of 1) or the composition of 2) is administered by intravenous, intraperitoneal, transmucosal, oral, subcutaneous, pulmonary, intranasal, intradermal or intramuscular administration.
9. The method of claim 1, wherein the polymeric nanoparticles comprise polymer that is a non-methoxy-terminated polymer.
121. The method of claim 117, wherein the polymeric synthetic nanocarriers comprise polymer that is a non-methoxy-terminated, pluronic polymer.
10. The method of claim 1, wherein the polymeric nanoparticles comprise a polyester, a polyester coupled to a polyether, polyamino acid, polycarbonate, polyacetal, polyketal, polysaccharide, polyethyloxazoline or polyethyleneimine.
11. The method of claim 10, wherein the polyester comprises a poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid) or polycaprolactone.
12. The method of claim 10, wherein the polymeric nanoparticles comprise a polyester and a polyester coupled to a polyether.
13. The method of any of claims 10-12, wherein the polyether comprises polyethylene glycol or polypropylene glycol.
122. The method of claim 117, wherein the polymeric synthetic nanocarriers comprise a polyester, a polyester coupled to a polyether, polyamino acid, polycarbonate, polyacetal, polyketal, polysaccharide, polyethyloxazoline or polyethyleneimine.
123. The method of claim 122, wherein the polyester comprises a poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid) or polycaprolactone.
124. The method of claim 122 or 123, wherein the polymeric synthetic nanocarriers comprise a polyester and a polyester coupled to a polyether.
125. The method of claim 124, wherein the polyether comprises polyethylene glycol or polypropylene glycol.
14. The method of claim 1, wherein the aspect ratio of the maximum to minimum dimensions of the synthetic nanocarriers is greater than 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10.
129. The method of claim 117, wherein the aspect ratio of the synthetic polymeric nanocarriers is greater than 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10.
15. The method of claim 1, wherein at least 80% of the polymeric synthetic nanocarriers, based on the total number of polymeric synthetic nanocarriers, have a minimum dimension or maximum dimension that falls within 20% of the average minimum dimension or the average maximum dimension, respectively, of the polymeric synthetic nanocarriers.
16. The method of claim 15, wherein at least 90% or at least of the polymeric synthetic nanocarriers have the minimum dimension or maximum dimension.
17. The method of claim 16, wherein at least 95% of the polymeric synthetic nanocarriers have the minimum dimension or maximum dimension.
18. The method of claim 16, wherein the minimum dimension or maximum dimension falls within 10%.
19. The method of claim 18, wherein the minimum dimension or maximum dimension falls within 5%.
128. The method of claim 127, wherein at least 80%, at least 90%, or at least 95% of the synthetic nanocarriers have a minimum dimension or maximum dimension that falls within 5%, 10%, or 20% of the mean diameter of the synthetic nanocarriers.
Applicant's arguments filed January 12, 2026 have been fully considered but they are not persuasive. Applicant proposes that this rejection be deferred until allowable subject matter has been identified and maintains the right to subsequently address these rejections (see, MPEP § 804), if necessary.
Additionally, Applicant notes that a nonstatutory double patenting rejection is based on a comparison of the claims of the application with the claims of the reference patent or patent application. For example, MPEP 804 (II)(B) states that "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)." Applicant respectfully submits that the Office has not established that the claims of the instant application are anticipated or rendered obvious by the claims of the above-referenced patents or patent applications.
In response, the request that this rejection be held in abeyance until allowable subject matter has been identified is acknowledged.
Contrary to applicant’s assertion that the office has not established that the claims of instant application are anticipated or rendered obvious by the referenced patent above, the claim by claim analysis above clearly established that the claims of instant application are anticipated by the issued claims because the therapeutic protein APC presentable antigen (species) encompassed by the claimed method anticipate the therapeutic protein encompassed (genus) by the method of the issued patent.
For these reasons and reasons of record, the rejection is maintained.
Claims 117, 119-126 and 128-132 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-8, 10-15 of U.S. Patent No. 10,441,651. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the issued patent (species) anticipate the claims under examination (genus).
.
10,441,651
18/177,714
1. A method comprising: (A) administering to a subject a composition that comprises: (i) a first population of polymeric synthetic nanocarriers coupled to rapamycin or an analog thereof, and (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen (species), wherein the composition is in an amount effective to generate antigen-specific CD8+ regulatory T cells in the subject; or
(B) generating antigen-specific CD8+ regulatory T cells in a subject by administering a composition that comprises: (i) a first population of polymeric synthetic nanocarriers coupled to rapamycin or an analog thereof, and (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen; or
(C) administering to a subject a composition according to a protocol that was previously shown to generate antigen-specific CD8+ regulatory T cells in one or more test subjects;
wherein the composition comprises: (i) a first population of polymeric synthetic nanocarriers coupled to rapamycin or an analog thereof, and (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen; and
wherein the load of the rapamycin or an analog thereof on average across the first population of polymeric synthetic nanocarriers is at least 2% but no more than 25% (weight/weight), and wherein at least 75% of the polymeric synthetic nanocarriers of the first population of polymeric synthetic nanocarriers have a minimum dimension, obtained using dynamic light scattering, that is greater than 110 nm and a maximum dimension, obtained using dynamic light scattering, that is equal to or less than 500 nm.
Administering a composition comprising the same therapeutic protein concomitantly with a composition comprising the same rapamycin or analog thereof coupled to polymeric nanocarrier is expected to reduce the generation of therapeutic protein specific undesired immune response.
117. (Currently Amended) a method for reducing the generation of an undesired immune response to a therapeutic protein in a subject comprising administering to the subject:
1) a composition comprising a population of polymeric synthetic nanocarriers that are coupled to rapamycin or a rapamycin analog, and
2) a composition comprising a therapeutic protein APC presentable antigen, which therapeutic protein APC presentable antigen comprises a therapeutic protein; wherein the load of the rapamycin or rapamycin analog on average across the population of polymeric synthetic nanocarriers is at least 2% but no more than 25% (weight/weight),wherein the polymeric synthetic nanocarriers have a minimum dimension, obtained using dynamic light scattering, that is greater than 110 nm, and a maximum dimension, obtained using dynamic light scattering, that is equal to or less than 500 nm, and wherein the composition of 1) and the composition of 2) are administered concomitantly and wherein the composition is in an amount effective to reduce the generation of an undesired immune response against the therapeutic protein.
119. (Currently Amended) The method of claim 117, wherein the therapeutic protein is an enzyme (species).
120. The method of claim 117, wherein the undesired immune response is the generation of therapeutic protein-specific antibodies and/or CD4+ T cell proliferation and/or activity and/or B cell proliferation and/or activity is reduced in the subject.
126. The method of claim 117, wherein the mean of a particle size distribution obtained using dynamic light scattering of the population of synthetic polymeric nanocarriers is a diameter is greater than 150 nm.
130. The method of claim 117, wherein the composition of 1) or 2) further comprises a pharmaceutically acceptable excipient.
2. The method of claim 1, wherein the method further comprises providing or identifying the subject.
See para. [0022].
3. The method of claim 1, wherein the antigen is a therapeutic protein, an autoantigen or an allergen, or is associated with an inflammatory disease, an autoimmune disease, organ or tissue rejection or graft versus host disease.
119. (Currently Amended) The method of claim 117, wherein the therapeutic protein is an infusible or injectable therapeutic protein (genus), enzyme, enzyme cofactor, hormone, blood or blood coagulation factor, cytokine, interferon, growth factor, monoclonal antibody, or polyclonal antibody (species).
4. The method of claim 1, wherein the method further comprises assessing the generation of antigen-specific CD8+ regulatory T cells in the subject prior to and/or after the administration of the composition.
5. The method of claim 1, wherein the subject has or is at risk of having an inflammatory disease, an autoimmune disease, an allergy, organ or tissue rejection or graft versus host disease; the subject has undergone or will undergo transplantation; and/or the subject has or is at risk of having an undesired immune response against a therapeutic protein that is being administered or will be administered to the subject.
See claim 117
6. The method of claim 1, wherein one or more maintenance doses of the composition comprising the first population of synthetic nanocarriers and MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen is administered to the subject.
See claim 117
7. The method of claim 1, wherein the administering is by intravenous, intraperitoneal, transmucosal, oral, subcutaneous, pulmonary, intranasal, intradermal or intramuscular administration.
131. The method of claim 117, wherein the composition of 1) or the composition of 2) is administered by intravenous, intraperitoneal, transmucosal, oral, subcutaneous, pulmonary, intranasal, intradermal or intramuscular administration.
8. The method of claim 1, wherein the administering is by inhalation or intravenous, subcutaneous or transmucosal administration.
See claim 131.
9. The method of claim 1, wherein the method further comprises collecting the generated antigen-specific CD8+ regulatory T cells.
10. The method of claim 1, wherein the polymeric synthetic nanocarriers comprise polymer that is a non-methoxy-terminated polymer.
121. The method of claim 117, wherein the polymeric synthetic nanocarriers comprise polymer that is a non-methoxy-terminated, pluronic polymer.
11. The method of claim 1, wherein the polymeric synthetic nanocarriers comprise a polyester, a polyester coupled to a polyether, polyamino acid, polycarbonate, polyacetal, polyketal, polysaccharide, polyethyloxazoline or polyethyleneimine.
122. The method of claim 117, wherein the polymeric synthetic nanocarriers comprise a polyester, a polyester coupled to a polyether, polyamino acid, polycarbonate, polyacetal, polyketal, polysaccharide, polyethyloxazoline or polyethyleneimine.
12. The method of claim 11, wherein the polyester comprises a poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid) or polycaprolactone.
13. The method of claim 11, wherein the polymeric synthetic nanocarriers comprise a polyester and a polyester coupled to a polyether.
14. The method of claim 13, wherein the polyether comprises polyethylene glycol or polypropylene glycol.
15. The method of claim 1, wherein the aspect ratio of the synthetic nanocarriers of the first population is greater than 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10.
123. The method of claim 122, wherein the polyester comprises a poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid) or polycaprolactone.
124. The method of claim 122 or 123, wherein the polymeric synthetic nanocarriers comprise a polyester and a polyester coupled to a polyether.
125. The method of claim 124, wherein the polyether comprises polyethylene glycol or polypropylene glycol.
129. The method of claim 117, wherein the aspect ratio of the synthetic polymeric nanocarriers is greater than 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10.
Applicant's arguments filed January 12, 2026 have been fully considered but they are not persuasive. Applicant proposes that this rejection be deferred until allowable subject matter has been identified and maintains the right to subsequently address these rejections (see, MPEP § 804), if necessary.
Additionally, Applicant notes that a nonstatutory double patenting rejection is based on a comparison of the claims of the application with the claims of the reference patent or patent application. For example, MPEP 804 (II)(B) states that "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)." Applicant respectfully submits that the Office has not established that the claims of the instant application are anticipated or rendered obvious by the claims of the above-referenced patents or patent applications.
In response, the request that this rejection be held in abeyance until allowable subject matter has been identified is acknowledged.
Contrary to applicant’s assertion that the office has not established that the claims of instant application are anticipated or rendered obvious by the referenced patent above, the claim by claim analysis above clearly established that the claims of instant application are anticipated by the claims of the referenced patent.
For these reasons and reasons of record, the rejection is maintained.
Claims 117, 119-126 and 128-132 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 6-10, 12-19 of U.S. Patent No. 11,717,569. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims differ only in scope. The claims under examination limit the immunosuppressant to rapamycin or rapamycin analog (species) whereas the issued claim is generic with respect to the immunosuppressant (genus).
11,717,569
18/177,714
1. A method comprising administering to a subject: i) a composition comprising a first population of polymeric synthetic nanocarriers coupled to an immunosuppressant wherein the immunosuppressant is rapamycin or a rapamycin analog, and ii) an APC presentable antigen, wherein the load of immunosuppressant on average across the first population of polymeric synthetic nanocarriers is at least 2% but no more than 25% (weight/weight), and wherein at least 75% of the polymeric synthetic nanocarriers of the first population have a minimum dimension, obtained using dynamic light scattering, that is greater than 110 nm and a maximum dimension, obtained using dynamic light scattering, that is equal to or less than 500 nm, wherein the subject is in need of antigen-specific tolerance.
117. (Currently Amended) a method for reducing the generation of an undesired immune response to a therapeutic protein in a subject comprising administering to the subject:
1) a composition comprising a population of polymeric synthetic nanocarriers that are coupled to rapamycin or a rapamycin analog (species), and 2) a composition comprising a therapeutic protein APC presentable antigen, which therapeutic protein APC presentable antigen comprises a therapeutic protein; wherein the load of the rapamycin or rapamycin analog on average across the population of polymeric synthetic nanocarriers is at least 2% but no more than 25% (weight/weight),wherein the polymeric synthetic nanocarriers have a minimum dimension, obtained using dynamic light scattering, that is greater than 110 nm, and a maximum dimension, obtained using dynamic light scattering, that is equal to or less than 500 nm, and wherein the composition of 1) and the composition of 2) are administered concomitantly and wherein the composition is in an amount effective to reduce the generation of an undesired immune response against the therapeutic protein.
119. (Currently Amended) The method of claim 117, wherein the therapeutic protein APC presentable antigen is an enzyme (species).
120. The method of claim 117, wherein the undesired immune response is the generation of therapeutic protein-specific antibodies and/or CD4+ T cell proliferation and/or activity and/or B cell proliferation and/or activity is reduced in the subject.
126. (Currently Amended) The method of claim 117, wherein a mean of a particle size distribution obtained using dynamic light scattering of the population of synthetic polymeric nanocarriers is a diameter is greater than 150 nm.
130. The method of claim 117, wherein the composition of 1) or 2) further comprises a pharmaceutically acceptable excipient.
2. The method of claim 1, wherein the composition is administered in an amount effective to result in a tolerogenic immune response specific to the APC presentable antigen.
See Claim 117.
Aka reducing generation of undesired immune response.
3. The method of claim 1, wherein the composition is administered to the subject according to a protocol that was previously shown to result in a tolerogenic immune response specific to the APC presentable antigen in one or more test subjects.
See para. [0021]
4. The method of claim 1, wherein the method further comprises providing or identifying the subject.
See para. [0022]
5. The method of claim 1, wherein the method further comprises assessing the generation of the tolerogenic immune response specific to the APC presentable antigen in the subject.
See para. [0114]
6. The method of claim 1, wherein the subject has an autoimmune disease, an inflammatory disease, an allergy, organ or tissue rejection, graft versus host disease or has undergone or is expected to undergo transplantation.
See para. [0116].
7. The method of claim 1, wherein the subject has received, is receiving or is expected to receive a therapeutic protein against which they have experienced, are experiencing or are expected to experience an undesired immune response.
See claim 117
8. The method of claim 1, wherein the dosage form is administered by intravenous, transmucosal, intraperitoneal, oral, subcutaneous, pulmonary, intranasal, intradermal, or intramuscular administration.
131. (New) The method of claim 117, wherein the composition of 1) or the composition of 2) is administered by intravenous, intraperitoneal, transmucosal, oral, subcutaneous, pulmonary, intranasal, intradermal or intramuscular administration.
9. The method of claim 1, wherein the administering is by inhalation, intravenous, subcutaneous, or transmucosal administration.
See claim 131
10. The method of claim 1, wherein the immunosuppressant in the composition is in an amount effective to generate a tolerogenic immune response to the APC presentable antigen.
See claim 117
11. The method of claim 1, wherein the APC presentable antigen is coupled to synthetic nanocarriers of the first population of synthetic nanocarriers and/or synthetic nanocarriers of a second population of synthetic nanocarriers.
12. The method of claim 1, wherein the APC presentable antigen: comprises an MHC class I-restricted and/or MHC class II-restricted epitope; is a lipid that binds to CD1d; and/or is a therapeutic protein or portion thereof, an autoantigen or an allergen or is associated with an autoimmune disease, an inflammatory disease, an allergy, organ or tissue rejection or graft versus host disease.
13. The method of claim 1, wherein the polymeric synthetic nanocarriers of the first population of polymeric synthetic nanocarriers comprise polymer that is a non-methoxy-terminated, ethylene oxide and propylene oxide copolymer.
14. The method of claim 13, wherein the polymeric synthetic nanocarriers comprise a polyester, a polyester coupled to a polyether, polyamino acid, polycarbonate, polyacetal, polyketal, polysaccharide, polyethyloxazoline or polyethyleneimine.
15. The method of claim 1, wherein at least 80% of the synthetic nanocarriers, based on the total number of synthetic nanocarriers, have a minimum dimension or maximum dimension that falls within 20% of the average minimum dimension or the average maximum dimension, respectively of the synthetic nanocarriers.
16. The method of claim 15, wherein at least 90% of the synthetic nanocarriers have the minimum dimension or maximum dimension.
17. The method of claim 16, wherein at least 95% of the synthetic nanocarriers have the minimum dimension or maximum dimension.
18. The method of claim 16, wherein the minimum dimension or maximum dimension falls within 10%.
19. The method of claim 18, wherein the minimum dimension or maximum dimension falls within 5%.
See claim 117.
121. (New) The method of claim 117, wherein the polymeric synthetic nanocarriers comprise polymer that is a non-methoxy-terminated, pluronic polymer.
122. (New) The method of claim 117, wherein the polymeric synthetic nanocarriers comprise a polyester, a polyester coupled to a polyether, polyamino acid, polycarbonate, polyacetal, polyketal, polysaccharide, polyethyloxazoline or polyethyleneimine.
128. (New) The method of claim 127, wherein at least 80%, at least 90%, or at least 95% of the synthetic nanocarriers have a minimum dimension or maximum dimension that falls within 5%, 10%, or 20% of the mean diameter of the synthetic nanocarriers.
Applicant's arguments filed January 12, 2026 have been fully considered but they are not persuasive. Applicant proposes that this rejection be deferred until allowable subject matter has been identified and maintains the right to subsequently address these rejections (see, MPEP § 804), if necessary.
Additionally, Applicant notes that a nonstatutory double patenting rejection is based on a comparison of the claims of the application with the claims of the reference patent or patent application. For example, MPEP 804 (II)(B) states that "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)." Applicant respectfully submits that the Office has not established that the claims of the instant application are anticipated or rendered obvious by the claims of the above-referenced patents or patent applications.
In response, the request that this rejection be held in abeyance until allowable subject matter has been identified is acknowledged.
Contrary to applicant’s assertion that the office has not established that the claims of instant application are anticipated or rendered obvious by the referenced patent above, the claim by claim analysis above clearly established that the claims are not patently distinct from each other.
For these reasons and reasons of record, the rejection is maintained.
Claims 117, 119-126 and 128-132 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,668,053. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims differ only in scope. The examined claims (species) are anticipated by the issued claims (genus).
10,668,053
18/177,714
1. A method for reducing or preventing an anaphylactic reaction to a non-allergenic antigen, comprising: providing the non-allergenic antigen (genus), the non-allergenic antigen being unattached to synthetic nanocarriers; providing a composition comprising synthetic nanocarriers attached to an mTOR inhibitor (genus); 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 (genus).
6. The method of claim 1, wherein the non-allergenic antigen comprises a therapeutic macromolecule.
7. The method of claim 6, wherein the therapeutic macromolecule is a therapeutic protein or a therapeutic polynucleotide.
13. The method claim 1, wherein a load of mTOR inhibitor attached to the synthetic nanocarriers, on average across the synthetic nanocarriers, is between 0.1% and 50%.
The reference protein for replacement or protein supplementation therapy, enzyme, enzyme cofactor, hormone, blood or blood coagulation factor, cytokine, interferon, growth factor, monoclonal antibody, or polyclonal antibody inherently comprises MHC class I and MHC class II epitopes, B cell epitope, and presentable by antigen presenting cells (APC) such as macrophage and dendritic cells and
117. (Currently Amended) a method for reducing the generation of an undesired immune response to a therapeutic protein in a subject comprising administering to the subject:
1) a composition comprising a population of polymeric synthetic nanocarriers that are coupled to rapamycin (species) or a rapamycin analog (species), and
2) a composition comprising a therapeutic protein APC presentable antigen (species); wherein the load of the rapamycin or rapamycin analog on average across the population of polymeric synthetic nanocarriers is at least 2% but no more than 25% (weight/weight),wherein the polymeric synthetic nanocarriers have a minimum dimension, obtained using dynamic light scattering, that is greater than 110 nm, and a maximum dimension, obtained using dynamic light scattering, that is equal to or less than 500 nm, and wherein the composition of 1) and the composition of 2) are administered concomitantly and wherein the composition is in an amount effective to reduce the generation of an undesired immune response against the therapeutic protein.
119. (Currently Amended) The method of claim 117, wherein the therapeutic protein is an enzyme.
2. The method of claim 1, wherein the concomitant administration to the subject is according to a protocol that has been demonstrated to reduce or prevent an anaphylactic reaction.
See para. [0021]
3. The method of claim 1, wherein the method further comprises assessing the anaphylactic reaction in the subject prior to and/or after the administration.
See para. [0018]
4. The method of claim 1, wherein the administering is by intravenous, intraperitoneal or subcutaneous administration.
131. The method of claim 117, wherein the composition of 1) or the composition of 2) is administered by intravenous, intraperitoneal, transmucosal, oral, subcutaneous, pulmonary, intranasal, intradermal or intramuscular administration.
5. The method of claim 1, wherein the method further comprises recording a reduction or prevention of an anaphylactic reaction to the non-allergenic antigen.
See para. [0037]. It is within the purview of one of ordinary skill in the pharmaceutical art to record any reduction of any anaphylactic reaction to the protein antigen administered to the subject.
8. The method of claim 7, wherein the therapeutic protein comprises a/an infusible or injectable therapeutic protein, a protein for protein replacement or protein supplementation therapy, enzyme, enzyme cofactor, hormone, blood or blood coagulation factor, cytokine, interferon, growth factor, monoclonal antibody, polyclonal antibody, or protein associated with Pompe's disease.
119. (Currently Amended) The method of claim 117, wherein the therapeutic protein is an enzyme.
9. The method of claim 8, wherein the infusible or injectable therapeutic protein comprises Tocilizumab, alpha-1 antitrypsin, Hematide, albinterferon alfa-2b, Thucin, tesamorelin, ocrelizumab, belimumab, pegloticase, taliglucerase alfa, agalsidase alfa, velaglucerase alfa, imiglucerase, a-galactosidase A (a-gal A), agalsidase beta, acid α-glucosidase (GAA), alglucosidase alfa, arylsulfatase B, laronidase, idursulfase, arylsulfatase B, pegsiticase or galsulfase.
10. The method of claim 8, wherein the enzyme comprises an oxidoreductase, transferase, hydrolase, lysase, isomerase, ligase or an enzyme for enzyme replacement therapy for a lysosomal storage disorder.
11. The method of claim 8, wherein the cytokine comprises a lymphokine, interleukin, chemokine, type 1 cytokine or a type 2 cytokine.
12. The method of claim 8, wherein the blood or blood coagulation factor comprises Factor I, Factor II, tissue factor, Factor V, Factor VII, Factor VIII, Factor IX, Factor X, Factor Xa, Factor XII, Factor XIII, von Willebrand factor, prekallikrein, high-molecular weight kininogen, fibronectin, antithrombin III, heparin cofactor II, protein C, protein S, protein Z, protein Z-related protease inhibitor (ZPI), plasminogen, alpha 2-antiplasmin, tissue plasminogen activator (tPA), urokinase, plasminogen activator inhibitor-1 (PAI1), plasminogen activator inhibitor-2 (PAI2), cancer procoagulant or epoetin alfa (species).
See para. [0008]
14. The method of claim 1, wherein the synthetic nanocarriers comprise lipid nanoparticles, polymeric nanoparticles, metallic nanoparticles, surfactant-based emulsions, dendrimers, buckyballs, nanowires, virus-like particles or peptide or protein particles.
See para. [0012]
15. The method claim 1, wherein the mean of a particle size distribution obtained using dynamic light scattering of the synthetic nanocarriers is a diameter greater than 100 nm.
126. (Currently Amended) The method of claim 117, wherein a mean of a particle size distribution obtained using dynamic light scattering of the population of synthetic polymeric nanocarriers is a diameter is greater than 150 nm.
16. The method of claim 1, wherein an aspect ratio of the synthetic nanocarriers is greater than 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10.
129. The method of claim 117, wherein the aspect ratio of the synthetic polymeric nanocarriers is greater than 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10.
Applicant's arguments filed January 12, 2026 have been fully considered but they are not persuasive. Applicant proposes that this rejection be deferred until allowable subject matter has been identified and maintains the right to subsequently address these rejections (see, MPEP § 804), if necessary.
Additionally, Applicant notes that a nonstatutory double patenting rejection is based on a comparison of the claims of the application with the claims of the reference patent or patent application. For example, MPEP 804 (II)(B) states that "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)." Applicant respectfully submits that the Office has not established that the claims of the instant application are anticipated or rendered obvious by the claims of the above-referenced patents or patent applications.
In response, the request that this rejection be held in abeyance until allowable subject matter has been identified is acknowledged.
Contrary to applicant’s assertion that the office has not established that the claims of instant application are anticipated or rendered obvious by the referenced patent above, the claim by claim analysis above clearly established that the claims of instant application (species) anticipate the claims of the referenced patent (genus).
For these reasons and reasons of record, the rejection is maintained.
Claims 117-126 and 128-132 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-20 of U.S. Patent No. 10,357,482. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims differ only in scope.
Instant specification defines “therapeutic protein” as follow:
[0112] A “therapeutic protein” refers to any protein or protein-based therapy that may be administered to a subject and have a therapeutic effect. Such therapies include protein replacement and protein supplementation therapies. Such therapies also include the administration of exogenous or foreign protein, antibody therapies, and cell or cell-based therapies. Therapeutic proteins include enzymes, enzyme cofactors, hormones, blood clotting factors, cytokines, growth factors, monoclonal antibodies and polyclonal antibodies. Examples of other therapeutic proteins are provided elsewhere herein. Therapeutic proteins may be produced in, on or by cells and may be obtained from such cells or administered in the form of such cells. In embodiments, the therapeutic protein is produced in, on or by mammalian cells, insect cells, yeast cells, bacteria cells, plant cells, transgenic animal cells, transgenic plant cells, etc. The therapeutic protein may be recombinantly produced in such cells. The therapeutic protein may be produced in, on or by a virally transformed cell. The therapeutic protein may also be produced in, on or by autologous cells that have been transfected, transduced or otherwise manipulated to express it. Alternatively, the therapeutic protein may be administered as a nucleic acid or by introducing a nucleic acid into a virus, VLP, liposome, etc. Alternatively, the therapeutic protein may be obtained from such forms and administered as the therapeutic protein itself. Subjects, therefore, include any subject that has received, is receiving or will receive any of the foregoing. Such subject includes subjects that have received, is receiving or will receive gene therapy, autologous cells that have been transfected, transduced or otherwise manipulated to express a therapeutic protein, polypeptide or peptide; or cells that express a therapeutic protein, polypeptide or peptide.
Instant specification defines “Therapeutic protein APC presentable antigen” as follow:
[0113] “Therapeutic protein APC presentable antigen” means an antigen that is associated with a therapeutic protein (i.e., the therapeutic protein or a fragment thereof can generate an immune response against the therapeutic protein (e.g., the production of therapeutic protein-specific antibodies)). Generally, therapeutic protein APC presentable antigens can be presented for recognition by the immune system (e.g., cells of the immune system, such as presented by antigen presenting cells, including but not limited to dendritic cells, B cells or macrophages). The therapeutic protein APC presentable antigen can be presented for recognition by, for example, T cells. Such antigens may be recognized by and trigger an immune response in a T cell via presentation of an epitope of the antigen bound to a Class I or Class II major histocompatibility complex molecule (MHC). Therapeutic protein APC presentable antigens generally include proteins, polypeptides, peptides, lipoproteins, or are contained or expressed in, on or by cells. The therapeutic protein antigens, in some embodiments, are coupled to synthetic nanocarriers and comprise MHC Class I-restricted epitopes and/or MHC Class II-restricted epitopes and/or B cell epitopes. In other embodiments, the antigens do not comprise B cell epitopes, such as when the inclusion of the B cell epitopes would exacerbate an undesired immune response. In other embodiments, the antigens comprise MHC Class II-restricted epitopes and substantially no B cell epitopes. Preferably, one or more tolerogenic immune responses specific to the therapeutic protein result with the compositions provided herein.
Regarding immunosuppressant, the instant specification defines as follow:
[0172] Any immunosuppressant as provided herein can be coupled to the synthetic nanocarrier. Immunosuppressants include, but are not limited to, statins; mTOR inhibitors, such as rapamycin or a rapamycin analog;
10,357,482
18/177,714
1. A method comprising: providing a therapeutic dose of a therapeutic macromolecule, wherein the therapeutic macromolecule (genus) is not attached to synthetic nanocarriers; providing a composition comprising synthetic nanocarriers that are attached to immunosuppressants (genus); and locally administering the composition and the therapeutic dose of the therapeutic macromolecule to a subject concomitantly, wherein the subject is at risk of a local inflammatory reaction due to the administration of the therapeutic dose of the therapeutic macromolecule, and wherein the local concomitant administration of the composition and the therapeutic dose of the therapeutic macromolecule reduces both Type 1 hypersensitivity and Type IV hypersensitivity (species) in the subject.
11. The method of claim 1, wherein the immunosuppressant comprises a statin, an mTOR inhibitor (subgenus), a TGF-β signaling agent, a corticosteroid, an inhibitor of mitochondrial function, a P38 inhibitor, an NF-κB inhibitor, an adenosine receptor agonist, a prostaglandin E2agonist, a phosphodiesterase 4 inhibitor, an HDAC inhibitor or a proteasome inhibitor.
12. The method of claim 1, wherein the therapeutic macromolecule is a therapeutic protein or a therapeutic polynucleotide.
13. The method of claim 1, wherein the therapeutic protein is for protein replacement of protein supplementation therapy.
17. The method of claim 1, wherein a load of immunosuppressant attached to the synthetic nanocarriers, on average across the synthetic nanocarriers, is between 0.1% and 50%.
117. (Currently Amended) a method for reducing the generation of an undesired immune response to a therapeutic protein in a subject comprising administering to the subject:1) a composition comprising a population of polymeric synthetic nanocarriers that are coupled to rapamycin or a rapamycin analog (species), and 2) a composition comprising a therapeutic protein APC presentable antigen (species); wherein the load of the rapamycin or rapamycin analog on average across the population of polymeric synthetic nanocarriers is at least 2% but no more than 25% (weight/weight),wherein the polymeric synthetic nanocarriers have a minimum dimension, obtained using dynamic light scattering, that is greater than 110 nm, and a maximum dimension, obtained using dynamic light scattering, that is equal to or less than 500 nm, and wherein the composition of 1) and the composition of 2) are administered concomitantly and wherein the composition is in an amount effective to reduce the generation of an undesired immune response against the therapeutic protein.
118. (Currently Amended) The method of claim 117, wherein the therapeutic protein APC presentable antigen comprises a (i) MHC Class I-restricted and/or MHC Class II-restricted epitope(s) of the therapeutic protein and/or (ii) B cell epitope(s) of the therapeutic protein.
2. The method of claim 1, wherein the subject is a naïve subject.
3. The method of claim 1, wherein the composition and the therapeutic dose of the therapeutic macromolecule are administered to the same location.
It is within the purview of one of ordinary skill in the pharmaceutical art to administer the two composition in the same or different location.
4. The method of claim 1, wherein the composition and the therapeutic dose of the therapeutic macromolecule are administered to different locations.
5. The method of claim 1, wherein the concomitant local administration is according to a protocol that has been demonstrated to result in a reduction of both Type 1 hypersensitivity and Type IV hypersensitivity with the composition and therapeutic dose of the therapeutic macromolecule, as compared to local administration of the therapeutic dose of the therapeutic macromolecule in the absence of concomitant local administration of the composition.
6. The method of claim 5, wherein the method further comprises determining the protocol.
See para. [0021]
7. The method of claim 1, wherein the method further comprises assessing a local inflammatory response in the subject prior to and/or after the administration.
See para. [0330]
8. The method of claim 7, wherein the method further comprises assessing Type 1 hypersensitivity and Type IV hypersensitivity in the subject prior to and/or after the administration.
See para. [0330].
9. The method of claim 1, wherein the method further comprises recording a reduction or prevention of a local inflammatory response.
10. The method of claim 9, wherein the method further comprises recording a reduction in both Type 1 hypersensitivity and Type IV hypersensitivity.
14. The method of claim 1, wherein the therapeutic protein comprises a/an infusible or injectable therapeutic protein, enzyme, enzyme cofactor, hormone, blood or blood coagulation factor, cytokine, interferon, growth factor, monoclonal antibody, polyclonal antibody, or protein associated with Pompe's disease.
15. The method claim 14, wherein the enzyme comprises an enzyme for enzyme replacement therapy for a lysosomal storage disorder.
16. The method of claim 14, wherein the cytokine comprises a lymphokine, interleukin, chemokine, type 1 cytokine or a type 2 cytokine.
119. (Currently Amended) The method of claim 117, wherein the therapeutic protein is an infusible or injectable therapeutic protein (genus), enzyme, enzyme cofactor, hormone, blood or blood coagulation factor, cytokine, interferon, growth factor, monoclonal antibody, or polyclonal antibody.
See para. [0008].
18. The method of claim 1, wherein the synthetic nanocarriers comprise lipid nanoparticles, polymeric nanoparticles, metallic nanoparticles, surfactant-based emulsions, dendrimers, buckyballs, nanowires, virus-like particles or peptide or protein particles.
See para. [0012]
19. The method of claim 1, wherein the mean of a particle size distribution obtained using dynamic light scattering of the synthetic nanocarriers is a diameter greater than 100 nm.
The term greater than 100 nm include greater than 150 nm.
126. (Currently Amended) The method of claim 117, wherein a mean of a particle size distribution obtained using dynamic light scattering of the population of synthetic polymeric nanocarriers is a diameter is greater than 150 nm.
20. The method of claim 1, wherein an aspect ratio of the synthetic nanocarriers (genus) is greater than 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10.
129. (New) The method of claim 117, wherein the aspect ratio of the synthetic polymeric nanocarriers (species) is greater than 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10.
Applicant's arguments filed January 12, 2026 have been fully considered but they are not persuasive. Applicant proposes that this rejection be deferred until allowable subject matter has been identified and maintains the right to subsequently address these rejections (see, MPEP § 804), if necessary.
Additionally, Applicant notes that a nonstatutory double patenting rejection is based on a comparison of the claims of the application with the claims of the reference patent or patent application. For example, MPEP 804 (II)(B) states that "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)." Applicant respectfully submits that the Office has not established that the claims of the instant application are anticipated or rendered obvious by the claims of the above-referenced patents or patent applications.
In response, the request that this rejection be held in abeyance until allowable subject matter has been identified is acknowledged.
Contrary to applicant’s assertion that the office has not established that the claims of instant application are anticipated or rendered obvious by the referenced patent above, the claim by claim analysis above clearly established that the claims of instant application (species) anticipate the claims of the referenced patent (genus).
For these reasons and reasons of record, the rejection is maintained.
Claims 117-126 and 128-132 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,039,822. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims differ only in scope.
Instant specification defines “therapeutic protein” as follow:
[0112] A “therapeutic protein” refers to any protein or protein-based therapy that may be administered to a subject and have a therapeutic effect. Such therapies include protein replacement and protein supplementation therapies. Such therapies also include the administration of exogenous or foreign protein, antibody therapies, and cell or cell-based therapies. Therapeutic proteins include enzymes, enzyme cofactors, hormones, blood clotting factors, cytokines, growth factors, monoclonal antibodies and polyclonal antibodies. Examples of other therapeutic proteins are provided elsewhere herein. Therapeutic proteins may be produced in, on or by cells and may be obtained from such cells or administered in the form of such cells. In embodiments, the therapeutic protein is produced in, on or by mammalian cells, insect cells, yeast cells, bacteria cells, plant cells, transgenic animal cells, transgenic plant cells, etc. The therapeutic protein may be recombinantly produced in such cells. The therapeutic protein may be produced in, on or by a virally transformed cell. The therapeutic protein may also be produced in, on or by autologous cells that have been transfected, transduced or otherwise manipulated to express it. Alternatively, the therapeutic protein may be administered as a nucleic acid or by introducing a nucleic acid into a virus, VLP, liposome, etc. Alternatively, the therapeutic protein may be obtained from such forms and administered as the therapeutic protein itself. Subjects, therefore, include any subject that has received, is receiving or will receive any of the foregoing. Such subject includes subjects that have received, is receiving or will receive gene therapy, autologous cells that have been transfected, transduced or otherwise manipulated to express a therapeutic protein, polypeptide or peptide; or cells that express a therapeutic protein, polypeptide or peptide.
Instant specification defines “Therapeutic protein APC presentable antigen” as follow:
[0113] “Therapeutic protein APC presentable antigen” means an antigen that is associated with a therapeutic protein (i.e., the therapeutic protein or a fragment thereof can generate an immune response against the therapeutic protein (e.g., the production of therapeutic protein-specific antibodies)). Generally, therapeutic protein APC presentable antigens can be presented for recognition by the immune system (e.g., cells of the immune system, such as presented by antigen presenting cells, including but not limited to dendritic cells, B cells or macrophages). The therapeutic protein APC presentable antigen can be presented for recognition by, for example, T cells. Such antigens may be recognized by and trigger an immune response in a T cell via presentation of an epitope of the antigen bound to a Class I or Class II major histocompatibility complex molecule (MHC). Therapeutic protein APC presentable antigens generally include proteins, polypeptides, peptides, lipoproteins, or are contained or expressed in, on or by cells. The therapeutic protein antigens, in some embodiments, are coupled to synthetic nanocarriers and comprise MHC Class I-restricted epitopes and/or MHC Class II-restricted epitopes and/or B cell epitopes. In other embodiments, the antigens do not comprise B cell epitopes, such as when the inclusion of the B cell epitopes would exacerbate an undesired immune response. In other embodiments, the antigens comprise MHC Class II-restricted epitopes and substantially no B cell epitopes. Preferably, one or more tolerogenic immune responses specific to the therapeutic protein result with the compositions provided herein.
Regarding immunosuppressant, the instant specification defines as follow:
[0172] Any immunosuppressant as provided herein can be coupled to the synthetic nanocarrier. Immunosuppressants include, but are not limited to, statins; mTOR inhibitors, such as rapamycin or a rapamycin analog;
10,039,822
18/177,714
1. A method of providing polymeric synthetic nanocarriers, comprising: (i) preparing polymeric synthetic nanocarriers that comprise an immunosuppressant (genus) coupled thereto; and (ii) administering the polymeric synthetic nanocarriers to a subject, wherein the load of the immunosuppressant on average across the first population of synthetic nanocarriers is at least 2% but no more than 25% (weight/weight), and wherein at least 80% of the polymeric synthetic nanocarriers, based on the total number of synthetic nanocarriers, have a minimum dimension or maximum dimension that falls within 20% of the average minimum dimension or the average maximum dimension, respectively, of the polymeric synthetic nanocarriers; and wherein the average minimum dimension of the polymeric synthetic nanocarriers, obtained using dynamic light scattering, is greater than 110 nm and the average maximum dimension of the polymeric synthetic nanocarriers, obtained using dynamic light scattering, is less than 500 nm.
12. The method of claim 1, wherein an APC presentable antigen is also administered to the subject.
14. The method of claim 13, wherein the load of the APC presentable antigen on average across the polymeric synthetic nanocarriers is between 1% and 10% (weight/weight).
24. The method of claim 1, wherein the APC presentable antigen is a therapeutic protein (genus) or portion thereof, an autoantigen or an allergen, or is associated with an autoimmune disease, an inflammatory disease, an allergy, organ or tissue rejection or graft versus host disease.
The APC presentable antigen therapeutic protein inherently comprises (i) MHC Class I-restricted and/or MHC Class II-restricted epitope(s) of a therapeutic protein; (ii) B cell epitope(s).
21. The method of claim 1, wherein the immunosuppressant comprises a statin, an mTOR inhibitor, a TGF-beta signaling agent, a corticosteroid, an inhibitor of mitochondrial function, a P38 inhibitor, an NF-kappa beta inhibitor, an adenosine receptor agonist, a prostaglandin E2 agonist, a phosphodiesterase 4 inhibitor, an HDAC inhibitor or a proteasome inhibitor.
22. The method of claim 21, wherein the immunosuppressant is an mTOR inhibitor.
23. The method of claim 22, wherein the mTOR inhibitor is rapamycin.
117. (Currently Amended) a method for reducing the generation of an undesired immune response to a therapeutic protein in a subject comprising administering to the subject:1) a composition comprising a population of polymeric synthetic nanocarriers that are coupled to rapamycin or a rapamycin analog (species), and 2) a composition comprising a therapeutic protein APC presentable antigen (species); wherein the load of the rapamycin or rapamycin analog on average across the population of polymeric synthetic nanocarriers is at least 2% but no more than 25% (weight/weight),wherein the polymeric synthetic nanocarriers have a minimum dimension, obtained using dynamic light scattering, that is greater than 110 nm, and a maximum dimension, obtained using dynamic light scattering, that is equal to or less than 500 nm, and wherein the composition of 1) and the composition of 2) are administered concomitantly and wherein the composition is in an amount effective to reduce the generation of an undesired immune response against the therapeutic protein.
119. (Currently Amended) The method of claim 117, wherein the therapeutic protein is an enzyme (species).
126. (Currently Amended) The method of claim 117, wherein a mean of a particle size distribution obtained using dynamic light scattering of the population of synthetic polymeric nanocarriers is a diameter is greater than 150 nm.
130. The method of claim 117, wherein the composition of 1) or 2) further comprises a pharmaceutically acceptable excipient.
2. The method of claim 1, wherein at least 90% of the polymeric synthetic nanocarriers have the minimum dimension or maximum dimension.
3. The method of claim 2, wherein at least 95% of the polymeric synthetic nanocarriers have the minimum dimension or maximum dimension.
4. The method of claim 1, wherein the minimum dimension or maximum dimension falls within 10%.
5. The method of claim 4, wherein the minimum dimension or maximum dimension falls within 5%.
128. The method of claim 127, wherein at least 80%, at least 90%, or at least 95% of the synthetic nanocarriers have a minimum dimension or maximum dimension that falls within 5%, 10%, or 20% of the mean diameter of the synthetic nanocarriers.
6. The method of claim 1, wherein the average minimum dimension is equal to or greater than 120 nm.
7. The method of claim 6, wherein the average minimum dimension is equal to or greater than 130 nm.
8. The method of claim 7, wherein the average minimum dimension is equal to or greater than 150 nm.
9. The method of claim 8, wherein the average minimum dimension is greater than 200 nm.
10. The method of claim 9, wherein the average minimum dimension is greater than 250 nm.
126. (Currently Amended) The method of claim 117, wherein a mean of a particle size distribution obtained using dynamic light scattering of the population of synthetic polymeric nanocarriers is a diameter is greater than 150 nm.
15. The method of claim 1, wherein the polymeric synthetic nanocarriers comprise a polymer that is a non-methoxy-terminated, pluronic polymer.
121. The method of claim 117, wherein the polymeric synthetic nanocarriers comprise polymer that is a non-methoxy-terminated, pluronic polymer.
16. The method of claim 1, wherein the polymeric synthetic nanocarriers comprise a polyester, polycarbonate, polyamide or polyether.
17. The method of claim 16, wherein the polyester comprises a poly(lactic acid), poly(glycolic acid), poly(lactic-co-glycolic acid) or polycaprolactone.
18. The method of claim 17, wherein the polymeric nanoparticles comprise a polyester and a polyester attached to a polyether.
19. The method of claim 18, wherein the polyether comprises polyethylene glycol or polypropylene glycol.
122. The method of claim 117, wherein the polymeric synthetic nanocarriers comprise a polyester, a polyester coupled to a polyether, polyamino acid, polycarbonate, polyacetal, polyketal, polysaccharide, polyethyloxazoline or polyethyleneimine.
See para. [0139] to [0140]
See claim 122
See para. [0138].
20. The method of claim 1, wherein the aspect ratio on average across the polymeric synthetic nanocarriers is greater than 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10.
129. The method of claim 117, wherein the aspect ratio of the synthetic polymeric nanocarriers (species) is greater than 1:1, 1:1.2, 1:1.5, 1:2, 1:3, 1:5, 1:7 or 1:10.
Applicant's arguments filed January 12, 2026 have been fully considered but they are not persuasive. Applicant proposes that this rejection be deferred until allowable subject matter has been identified and maintains the right to subsequently address these rejections (see, MPEP § 804), if necessary.
Additionally, Applicant notes that a nonstatutory double patenting rejection is based on a comparison of the claims of the application with the claims of the reference patent or patent application. For example, MPEP 804 (II)(B) states that "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)." Applicant respectfully submits that the Office has not established that the claims of the instant application are anticipated or rendered obvious by the claims of the above-referenced patents or patent applications.
In response, the request that this rejection be held in abeyance until allowable subject matter has been identified is acknowledged.
Contrary to applicant’s assertion that the office has not established that the claims of instant application are anticipated or rendered obvious by the referenced patent above, the claim by claim analysis above clearly established that the claims of instant application (species) anticipate the claims of the referenced patent (genus).
For these reasons and reasons of record, the rejection is maintained.
Claims 117-126 and 128-132 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims *** of U.S. Patent No. ***. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims differ only in scope.
Instant specification defines “therapeutic protein” as follow:
[0112] A “therapeutic protein” refers to any protein or protein-based therapy that may be administered to a subject and have a therapeutic effect. Such therapies include protein replacement and protein supplementation therapies. Such therapies also include the administration of exogenous or foreign protein, antibody therapies, and cell or cell-based therapies. Therapeutic proteins include enzymes, enzyme cofactors, hormones, blood clotting factors, cytokines, growth factors, monoclonal antibodies and polyclonal antibodies. Examples of other therapeutic proteins are provided elsewhere herein. Therapeutic proteins may be produced in, on or by cells and may be obtained from such cells or administered in the form of such cells. In embodiments, the therapeutic protein is produced in, on or by mammalian cells, insect cells, yeast cells, bacteria cells, plant cells, transgenic animal cells, transgenic plant cells, etc. The therapeutic protein may be recombinantly produced in such cells. The therapeutic protein may be produced in, on or by a virally transformed cell. The therapeutic protein may also be produced in, on or by autologous cells that have been transfected, transduced or otherwise manipulated to express it. Alternatively, the therapeutic protein may be administered as a nucleic acid or by introducing a nucleic acid into a virus, VLP, liposome, etc. Alternatively, the therapeutic protein may be obtained from such forms and administered as the therapeutic protein itself. Subjects, therefore, include any subject that has received, is receiving or will receive any of the foregoing. Such subject includes subjects that have received, is receiving or will receive gene therapy, autologous cells that have been transfected, transduced or otherwise manipulated to express a therapeutic protein, polypeptide or peptide; or cells that express a therapeutic protein, polypeptide or peptide.
Instant specification defines “Therapeutic protein APC presentable antigen” as follow:
[0113] “Therapeutic protein APC presentable antigen” means an antigen that is associated with a therapeutic protein (i.e., the therapeutic protein or a fragment thereof can generate an immune response against the therapeutic protein (e.g., the production of therapeutic protein-specific antibodies)). Generally, therapeutic protein APC presentable antigens can be presented for recognition by the immune system (e.g., cells of the immune system, such as presented by antigen presenting cells, including but not limited to dendritic cells, B cells or macrophages). The therapeutic protein APC presentable antigen can be presented for recognition by, for example, T cells. Such antigens may be recognized by and trigger an immune response in a T cell via presentation of an epitope of the antigen bound to a Class I or Class II major histocompatibility complex molecule (MHC). Therapeutic protein APC presentable antigens generally include proteins, polypeptides, peptides, lipoproteins, or are contained or expressed in, on or by cells. The therapeutic protein antigens, in some embodiments, are coupled to synthetic nanocarriers and comprise MHC Class I-restricted epitopes and/or MHC Class II-restricted epitopes and/or B cell epitopes. In other embodiments, the antigens do not comprise B cell epitopes, such as when the inclusion of the B cell epitopes would exacerbate an undesired immune response. In other embodiments, the antigens comprise MHC Class II-restricted epitopes and substantially no B cell epitopes. Preferably, one or more tolerogenic immune responses specific to the therapeutic protein result with the compositions provided herein.
Regarding immunosuppressant, the instant specification defines as follow:
[0172] Any immunosuppressant as provided herein can be coupled to the synthetic nanocarrier. Immunosuppressants include, but are not limited to, statins; mTOR inhibitors, such as rapamycin or a rapamycin analog;
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHUONG HUYNH whose telephone number is (571)272-0846. The examiner can normally be reached on 9:00 a.m. to 6:30 p.m. The examiner can also be reached on alternate alternative Friday from 9:00 a.m. to 5:30 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Misook Yu, can be reached at 571-270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-272-0839.
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/PHUONG HUYNH/ Primary Examiner, Art Unit 1641
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