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 .
Claims Status
Applicant’s amendments and remarks filed 05/19/2026 are acknowledged.
Claims 112-116 and 119-131 are pending.
Claims 1-111 and 117-118 are cancelled.
Applicant’s election without traverse of Group III in the reply filed on 05/19/2026 is acknowledged. Applicant’s election of the following species without traverse in the reply filed on 05/19/2026 is acknowledged: SEQ ID NOs: 84-86 for the HCDRs 1-3, respectively, SEQ ID NOs: 87-89 for the LCDRs 1-3, respectively, SEQ ID NO: 90 for the heavy chain variable region, and SEQ ID NO: 91 for the light chain variable region. It is noted Applicant states in the response that the elected sequences for each of the CDRs and variable regions correspond to the anti-IGF-1R antibody of teprotumumab.
Claims 112-116 and 119-131 are under examination.
Priority
The instant application is a 371 of PCT/US2022/018737 and claims priority to provisional application 63/156,320. Priority is given with the earliest effective filing date of 03/03/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/05/2024, 04/25/2025, and 05/19/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Specification
The disclosure is objected to because it contains embedded hyperlinks and/or other forms of browser-executable code (see paragraph [0359] of the specification). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http://, www., or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 112 is objected to because of the following informalities: Claim 112 recites an acronym (i.e. IGF-1R, HCDR, LCDR). The first time an acronym is used, it must be accompanied by the definition of the abbreviation. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 112-116 and 119-131 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 112, 115, and 119 recite the limitation “a variant Fc region comprising a first mutation that is a tyrosine at position 252, a second mutation that is a threonine at position 254, and a third mutation that is a glutamic acid at position 256, wherein the amino acid substitution numbering is EU as in Kabat.” These claims are indefinite as there is no antecedent basis for the amino acid positions being recited. Amino acid numbering is not static or absolute so reference to a base sequence is necessary for antecedent basis of a reference to a position number.
Claims 113-114, 116 and 120-131, which depend from claims 112, 115, and 119, respectively, are therefore indefinite for the same reasons as set forth above.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 112-113, 115-116, 119-123, 125-127, and 129-130 are rejected under 35 U.S.C. 103 as being unpatentable over Douglas et al., 2020 (instant PTO-892) in view of Tsui (EP2844289A1; instant PTO-892).
Note: Applicant defines the claimed antibody comprising SEQ ID NOs: 84-86 for the HCDRs 1-3, respectively, SEQ ID NOs: 87-89 for the LCDRs 1-3, respectively, SEQ ID NO: 90 for the heavy chain variable domain, and SEQ ID NO: 91 for the light chain variable domain as teprotumumab [see paragraph 412 of the instant specification]. Therefore, the antibody as taught by Douglas, i.e. teprotumumab, is the same as the instantly claimed antibody.
Regarding claims 112, 115, 119, 121, 125, and 129, Douglas teaches administering the IGF-1R inhibitor teprotumumab, a fully human monoclonal antibody, to patients with active thyroid eye disease (TED), and that the administration of teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life (i.e. a method of treating TED) [see Abstract]. Douglas further teaches that 83% of the patients administered teprotumumab had a proptosis response [defined as a reduction in proptosis of ≥2 mm] (i.e. a method of reducing proptosis in a subject with TED) [page 345, Table 1; page 346, left column, second paragraph] and a higher percentage of patients administered teprotumumab has a diplopia response [defined as a reduction in diplopia ≥1 grade] (i.e. a method of treating diplopia in a subject with TED) [page 346, right column, second paragraph].
Since Douglas teaches that the teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life, that 83% of the patients administered teprotumumab had a proptosis response, and a higher percentage of patients administered teprotumumab has a diplopia response, then a therapeutically effective amount was necessarily administered.
However, Douglas does not specifically teach that the teprotumumab comprises a variant Fc region comprising a first mutation that is a tyrosine at position 252, a second mutation that is a threonine at position 254, and a third mutation that is a glutamic acid at position 256, wherein the amino acid substitution numbering is EU as in Kabat.
Tsui teaches a YTE mutant IgG1 Fc domain which comprises a combination of three mutations: M252Y, S254T, and T256E, wherein the numbering is according to the EU index as in Kabat, which results in an increase in the binding to human FcRn and improves the serum half-life of the antibody having the mutation [0065].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the teprotumumab of Douglas to comprise the Fc variant of Tsui. One would have been motivated to have made this modification in order to increase the binding to FcRn and thus, increase the serum retention of the antibody, as taught by Tsui.
Claim 113 is included in this rejection because Douglas teaches that the TED is active [see Abstract; Methods section].
Claims 116 and 126 are included in this rejection because they merely recite effects or results of administering the claimed antibody. Because it would have been obvious to have arrived at the claimed antibody as described above, a person of ordinary skill in the art would have reasonably expected these effects to occur, absent evidence to the contrary. Further, Douglas teaches that a patient administered teprotumumab achieved a reduction in proptosis of 5 mm [page 348; Figure 3].
Claim 120 is included in this rejection because Douglas teaches a patient receiving teprotumumab had a diplopia score of 3 (i.e. continuous diplopia) at baseline and at week 24 had a diplopia score of 0 (i.e. no diplopia) [page 348; Figure 3].
Claim 122 is included in this rejection because Douglas teaches that the patients had moderate-to-severe TED [page 342, right column, third paragraph].
Claims 123, 127, and 130 are included in this rejection because Douglas teaches that the teprotumumab is administered by intravenous infusion [see Abstract].
Claims 112-116, 119-123, 125-127, and 129-130 are rejected under 35 U.S.C. 103 as being unpatentable over Douglas et al., 2020 (instant PTO-892) in view of Tsui (EP2844289A1; instant PTO-892), as applied to claims 112-113, 115-116, 119-123, 125-127, and 129-130 above, and further in view of Ozzello et al., 2020 (instant PTO-892).
The teachings of Douglas and Tsui are above.
However, Douglas and Tsui do not specifically teach that the TED is inactive/chronic TED.
Regarding claim 114, Ozzello teaches treating a patient with chronic TED with teprotumumab resulting in improvement in proptosis and a decrease in extraocular muscle volume [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the teprotumumab comprising a variant Fc region, as taught by Douglas and Tsui, to the patient that has inactive/chronic TED of Ozzello. One would have been motivated to have administered the antibody of Douglas and Tsui to the patient that has inactive/chronic TED of Ozzello with a reasonable expectation of success because Ozzello teaches that a patient with chronic TED treated with teprotumumab had an improvement in proptosis and a decrease in extraocular muscle volume. Further, one would have been motivated to have treated the patient population having inactive/chronic TED with the antibody of Douglas and Tsui because this is a known patient population to treat with teprotumumab, as taught by Ozzello.
Claims 112-113, 115-116, and 119-131 are rejected under 35 U.S.C. 103 as being unpatentable over Douglas et al., 2020 (instant PTO-892) in view of Tsui (EP2844289A1; instant PTO-892), as applied to claims 112-113, 115-116, 119-123, 125-127, and 129-130 above, and further in view of Bittner et al., 2018 (instant PTO-892).
The teachings of Douglas and Tsui are above.
However, Douglas and Tsui do not specifically teach that the antibody is administered to the subject subcutaneously.
Regarding claims 124, 128, and 131, Bittner teaches that subcutaneous delivery has become a valuable alternative to intravenous administration and that while pharmacokinetic profiles differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the antibody, as taught by Douglas and Tsui, subcutaneously. One would have been motivated to have administered the antibody subcutaneously because Bittner teaches that subcutaneous delivery has become a valuable alternative to intravenous administration and that while pharmacokinetic profiles differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and results in reduced drug delivery-related healthcare costs and resource use.
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.
U.S. Patent No. 12,358,993, U.S. Patent No. 12,209,130, U.S. Patent No. 11,208,489, U.S. Patent No. 12,286,481, U.S. Patent No. 11,208,490, and U.S. Patent No. 12,600,787
Claims 112-113, 115-116, 119-123, 125-127, and 129-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No. 12,358,993, claims 1-28 of U.S. Patent No. 12,209,130, claims 1-24 of U.S. Patent No. 11,208,489, claims 1-28 of U.S. Patent No. 12,286,481, claims 1-11 of U.S. Patent No. 11,208,490, and claims 1-19 of U.S. Patent No. 12,600,787 in view of Douglas et al., 2020 (instant PTO-892) and Tsui (EP2844289A1; instant PTO-892).
Note: Applicant defines the claimed antibody comprising SEQ ID NOs: 84-86 for the HCDRs 1-3, respectively, SEQ ID NOs: 87-89 for the LCDRs 1-3, respectively, SEQ ID NO: 90 for the heavy chain variable domain, and SEQ ID NO: 91 for the light chain variable domain as teprotumumab [see paragraph 412 of the instant specification]. Therefore, the antibody as taught by U.S. Patent No. 12,358,993, U.S. Patent No. 12,209,130, U.S. Patent No. 11,208,489, U.S. Patent No. 12,286,481, U.S. Patent No. 11,208,490, U.S. Patent No. 12,600,787, and Douglas, i.e. teprotumumab, is the same as the instantly claimed antibody.
Regarding claims 112-113, 115-116, 119-123, 125-127, and 129-130, although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-38 of U.S. Patent No. 12,358,993, claims 1-28 of U.S. Patent No. 12,209,130, claims 1-24 of U.S. Patent No. 11,208,489, claims 1-28 of U.S. Patent No. 12,286,481, claims 1-11 of U.S. Patent No. 11,208,490, and claims 1-19 of U.S. Patent No. 12,600,787 each are drawn to a method of treating TED, a method of reducing the severity of diplopia in a subject with TED, and/or a method of reducing proptosis in a subject with TED comprising administering teprotumumab.
However, U.S. Patent No. 12,358,993, U.S. Patent No. 12,209,130, U.S. Patent No. 11,208,489, U.S. Patent No. 12,286,481, U.S. Patent No. 11,208,490, and U.S. Patent No. 12,600,787 do not each teach all of the methods of the independent claims (i.e. instant claims 112, 115, and 119) or that the teprotumumab comprises a variant Fc region comprising a first mutation that is a tyrosine at position 252, a second mutation that is a threonine at position 254, and a third mutation that is a glutamic acid at position 256, wherein the amino acid substitution numbering is EU as in Kabat.
Douglas teaches administering the IGF-1R inhibitor teprotumumab, a fully human monoclonal antibody, to patients with active thyroid eye disease (TED), and that the administration of teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life (i.e. a method of treating TED) [see Abstract]. Douglas further teaches that 83% of the patients administered teprotumumab had a proptosis response [defined as a reduction in proptosis of ≥2 mm] (i.e. a method of reducing proptosis in a subject with TED) [page 345, Table 1; page 346, left column, second paragraph] and a higher percentage of patients administered teprotumumab has a diplopia response [defined as a reduction in diplopia ≥1 grade] (i.e. a method of treating diplopia in a subject with TED) [page 346, right column, second paragraph].
Since Douglas teaches that the teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life, that 83% of the patients administered teprotumumab had a proptosis response, and a higher percentage of patients administered teprotumumab has a diplopia response, then a therapeutically effective amount was necessarily administered.
Tsui teaches a YTE mutant IgG1 Fc domain which comprises a combination of three mutations: M252Y, S254T, and T256E, wherein the numbering is according to the EU index as in Kabat, which results in an increase in the binding to human FcRn and improves the serum half-life of the antibody having the mutation [0065].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the teprotumumab of each of U.S. Patent No. 12,358,993, U.S. Patent No. 12,209,130, U.S. Patent No. 11,208,489, U.S. Patent No. 12,286,481, U.S. Patent No. 11,208,490, and U.S. Patent No. 12,600,787 in order to treat TED, reduce proptosis in a subject with TED, and treat diplopia in a subject with TED, as taught by Douglas. One would have been motivated to have administered the teprotumumab of each of the U.S. Patents to treat TED, reduce proptosis in a subject with TED, and treat diplopia in a subject with TED with a reasonable expectation of success because Douglas teaches that the administration of teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life (i.e. a method of treating TED), that 83% of the patients administered teprotumumab had a proptosis response [defined as a reduction in proptosis of ≥2 mm] (i.e. a method of reducing proptosis in a subject with TED), and a higher percentage of patients administered teprotumumab has a diplopia response [defined as a reduction in diplopia ≥1 grade] (i.e. a method of treating diplopia in a subject with TED). It further would have been obvious to have modified the teprotumumab of each of the U.S. Patents and Douglas to comprise the Fc variant of Tsui. One would have been motivated to have made this modification in order to increase the binding to FcRn and thus, increase the serum retention of the antibody, as taught by Tsui.
Claim 113 is included in this rejection because Douglas teaches that the TED is active [see Abstract; Methods section].
Claims 116 and 126 are included in this rejection because they merely recite effects or results of administering the claimed antibody. Because it would have been obvious to have arrived at the claimed antibody as described above, a person of ordinary skill in the art would have reasonably expected these effects to occur, absent evidence to the contrary. Further, Douglas teaches that a patient administered teprotumumab achieved a reduction in proptosis of 5 mm [page 348; Figure 3].
Claim 120 is included in this rejection because Douglas teaches a patient receiving teprotumumab had a diplopia score of 3 (i.e. continuous diplopia) at baseline and at week 24 had a diplopia score of 0 (i.e. no diplopia) [page 348; Figure 3].
Claim 122 is included in this rejection because Douglas teaches that the patients had moderate-to-severe TED [page 342, right column, third paragraph].
Claims 123, 127, and 130 are included in this rejection because Douglas teaches that the teprotumumab is administered by intravenous infusion [see Abstract].
14. Claims 112-116, 119-123, 125-127, and 129-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No. 12,358,993, claims 1-28 of U.S. Patent No. 12,209,130, claims 1-24 of U.S. Patent No. 11,208,489, claims 1-28 of U.S. Patent No. 12,286,481, claims 1-11 of U.S. Patent No. 11,208,490, and claims 1-19 of U.S. Patent No. 12,600,787 in view of Douglas et al., 2020 (instant PTO-892) and Tsui (EP2844289A1; instant PTO-892), as applied to claims 112-113, 115-116, 119-123, 125-127, and 129-130 above, and further in view of Ozzello et al., 2020 (instant PTO-892).
The teachings of U.S. Patent No. 12,358,993, U.S. Patent No. 12,209,130, U.S. Patent No. 11,208,489, U.S. Patent No. 12,286,481, U.S. Patent No. 11,208,490, U.S. Patent No. 12,600,787, Douglas, and Tsui are above. Further, claim 1 of U.S. Patent No. 12,358,993 teach that the subject has inactive/chronic TED.
However, U.S. Patent No. 12,209,130, U.S. Patent No. 11,208,489, U.S. Patent No. 12,286,481, U.S. Patent No. 11,208,490, U.S. Patent No. 12,600,787, Douglas, and Tsui do not specifically teach that the TED is inactive/chronic TED.
Regarding claim 114, Ozzello teaches treating a patient with chronic TED with teprotumumab resulting in improvement in proptosis and a decrease in extraocular muscle volume [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the teprotumumab comprising a variant Fc region, as taught by the U.S. Patents, Douglas, and Tsui, to the patient that has inactive/chronic TED of Ozzello. One would have been motivated to have administered the antibody of the U.S. Patents, Douglas, and Tsui to the patient that has inactive/chronic TED of Ozzello with a reasonable expectation of success because Ozzello teaches that a patient with chronic TED treated with teprotumumab had an improvement in proptosis and a decrease in extraocular muscle volume. Further, one would have been motivated to have treated the patient population having inactive/chronic TED with the antibody of the U.S. Patents, Douglas, and Tsui because this is a known patient population to treat with teprotumumab, as taught by Ozzello.
Claims 112-113, 115-116, and 119-131 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No. 12,358,993, claims 1-28 of U.S. Patent No. 12,209,130, claims 1-24 of U.S. Patent No. 11,208,489, claims 1-28 of U.S. Patent No. 12,286,481, claims 1-11 of U.S. Patent No. 11,208,490, and claims 1-19 of U.S. Patent No. 12,600,787 in view of Douglas et al., 2020 (instant PTO-892) and Tsui (EP2844289A1; instant PTO-892), as applied to claims 112-113, 115-116, 119-123, 125-127, and 129-130 above, and further in view of Bittner et al., 2018 (instant PTO-892).
The teachings of U.S. Patent No. 12,358,993, U.S. Patent No. 12,209,130, U.S. Patent No. 11,208,489, U.S. Patent No. 12,286,481, U.S. Patent No. 11,208,490, U.S. Patent No. 12,600,787, Douglas, and Tsui are above
However, U.S. Patent No. 12,358,993, U.S. Patent No. 12,209,130, U.S. Patent No. 11,208,489, U.S. Patent No. 12,286,481, U.S. Patent No. 11,208,490, U.S. Patent No. 12,600,787, Douglas, and Tsui do not specifically teach that the antibody is administered to the subject subcutaneously.
Regarding claims 124, 128, and 131, Bittner teaches that subcutaneous delivery has become a valuable alternative to intravenous administration and that while pharmacokinetic profiles differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the antibody, as taught by the U.S. Patents, Douglas, and Tsui, subcutaneously. One would have been motivated to have administered the antibody subcutaneously because Bittner teaches that subcutaneous delivery has become a valuable alternative to intravenous administration and that while pharmacokinetic profiles differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and results in reduced drug delivery-related healthcare costs and resource use.
Copending Application Nos. 18/324,056, 19/233,919, 19/373,528, and 19/639,842
Claims 112-113, 115-116, 119-123, 125-127, and 129-130 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 234 and 242 of copending Application No. 18/324,056, claims 41, 44, 49-52, and 56-57 of copending Application No. 19/233,919, claims 1 and 20 of copending Application No. 19/373,528, and claims 92 and 108-110 of copending Application No. 19/639,842 in view of Douglas et al., 2020 (instant PTO-892) and Tsui (EP2844289A1; instant PTO-892).
Note: Applicant defines the claimed antibody comprising SEQ ID NOs: 84-86 for the HCDRs 1-3, respectively, SEQ ID NOs: 87-89 for the LCDRs 1-3, respectively, SEQ ID NO: 90 for the heavy chain variable domain, and SEQ ID NO: 91 for the light chain variable domain as teprotumumab [see paragraph 412 of the instant specification]. Therefore, the antibody as taught by copending Application Nos. 18/324,056, 19/373,528, 19/233,919, 19/639,842, and Douglas, i.e. teprotumumab, is the same as the instantly claimed antibody.
Regarding claims 112-113, 115-116, 119-123, 125-127, and 129-130, although the claims at issue are not identical, they are not patentably distinct from each other because claims 234 and 242 of copending Application No. 18/324,056, claims 41, 44, 49-52, and 56-57 of copending Application No. 19/233,919, claims 1 and 20 of copending Application No. 19/373,528, and claims 92 and 108-110 of copending Application No. 19/639,842 each are drawn to a method of treating TED comprising administering teprotumumab.
However, copending Application Nos. 18/324,056, 19/373,528, 19/233,919, and 19/639,842 do not each teach all of the methods of the independent claims (i.e. instant claims 112, 115, and 119) or that the teprotumumab comprises a variant Fc region comprising a first mutation that is a tyrosine at position 252, a second mutation that is a threonine at position 254, and a third mutation that is a glutamic acid at position 256, wherein the amino acid substitution numbering is EU as in Kabat.
Douglas teaches administering the IGF-1R inhibitor teprotumumab, a fully human monoclonal antibody, to patients with active thyroid eye disease (TED), and that the administration of teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life (i.e. a method of treating TED) [see Abstract]. Douglas further teaches that 83% of the patients administered teprotumumab had a proptosis response [defined as a reduction in proptosis of ≥2 mm] (i.e. a method of reducing proptosis in a subject with TED) [page 345, Table 1; page 346, left column, second paragraph] and a higher percentage of patients administered teprotumumab has a diplopia response [defined as a reduction in diplopia ≥1 grade] (i.e. a method of treating diplopia in a subject with TED) [page 346, right column, second paragraph].
Since Douglas teaches that the teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life, that 83% of the patients administered teprotumumab had a proptosis response, and a higher percentage of patients administered teprotumumab has a diplopia response, then a therapeutically effective amount was necessarily administered.
Tsui teaches a YTE mutant IgG1 Fc domain which comprises a combination of three mutations: M252Y, S254T, and T256E, wherein the numbering is according to the EU index as in Kabat, which results in an increase in the binding to human FcRn and improves the serum half-life of the antibody having the mutation [0065].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the teprotumumab of each of copending Application Nos. 18/324,056, 19/373,528, 19/233,919, and 19/639,842 in order to treat TED, reduce proptosis in a subject with TED, and treat diplopia in a subject with TED, as taught by Douglas. One would have been motivated to have administered the teprotumumab of each of the copending Applicants to treat TED, reduce proptosis in a subject with TED, and treat diplopia in a subject with TED with a reasonable expectation of success because Douglas teaches that the administration of teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life (i.e. a method of treating TED), that 83% of the patients administered teprotumumab had a proptosis response [defined as a reduction in proptosis of ≥2 mm] (i.e. a method of reducing proptosis in a subject with TED), and a higher percentage of patients administered teprotumumab has a diplopia response [defined as a reduction in diplopia ≥1 grade] (i.e. a method of treating diplopia in a subject with TED). It further would have been obvious to have modified the teprotumumab of each of the copending applications and Douglas to comprise the Fc variant of Tsui. One would have been motivated to have made this modification in order to increase the binding to FcRn and thus, increase the serum retention of the antibody, as taught by Tsui.
Claim 113 is included in this rejection because Douglas teaches that the TED is active [see Abstract; Methods section].
Claims 116 and 126 are included in this rejection because they merely recite effects or results of administering the claimed antibody. Because it would have been obvious to have arrived at the claimed antibody as described above, a person of ordinary skill in the art would have reasonably expected these effects to occur, absent evidence to the contrary. Further, Douglas teaches that a patient administered teprotumumab achieved a reduction in proptosis of 5 mm [page 348; Figure 3].
Claim 120 is included in this rejection because Douglas teaches a patient receiving teprotumumab had a diplopia score of 3 (i.e. continuous diplopia) at baseline and at week 24 had a diplopia score of 0 (i.e. no diplopia) [page 348; Figure 3].
Claim 122 is included in this rejection because Douglas teaches that the patients had moderate-to-severe TED [page 342, right column, third paragraph].
Claims 123, 127, and 130 are included in this rejection because Douglas teaches that the teprotumumab is administered by intravenous infusion [see Abstract].
Claims 112-116, 119-123, 125-127, and 129-130 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 234 and 242 of copending Application No. 18/324,056, claims 41, 44, 49-52, and 56-57 of copending Application No. 19/233,919, claims 1 and 20 of copending Application No. 19/373,528, and claims 92 and 108-110 of copending Application No. 19/639,842 in view of Douglas et al., 2020 (instant PTO-892) and Tsui (EP2844289A1; instant PTO-892), as applied to claims 112-113, 115-116, 119-123, 125-127, and 129-130 above, claim 22 of copending Application No. 19/373,528, and further in view of Ozzello et al., 2020 (instant PTO-892).
The teachings of copending Application Nos. 18/324,056, 19/373,528, 19/233,919, 19/639,842, Douglas, and Tsui are above. Further, claim 22 of 19,373,528 teaches that patient is diagnosed with inactive thyroid eye disease and claim 92 of 19/639,842 teaches that the subject has inactive/chronic TED.
However, copending Application Nos. 18/324,056, 19/233,919, Douglas, and Tsui do not specifically teach that the TED is inactive/chronic TED.
Regarding claim 114, Ozzello teaches treating a patient with chronic TED with teprotumumab resulting in improvement in proptosis and a decrease in extraocular muscle volume [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the teprotumumab comprising a variant Fc region, as taught by the copending Applications, Douglas, and Tsui, to the patient that has inactive/chronic TED of Ozzello. One would have been motivated to have administered the antibody of the copending application, Douglas, and Tsui to the patient that has inactive/chronic TED of Ozzello with a reasonable expectation of success because Ozzello teaches that a patient with chronic TED treated with teprotumumab had an improvement in proptosis and a decrease in extraocular muscle volume. Further, one would have been motivated to have treated the patient population having inactive/chronic TED with the antibody of the copending Applications, Douglas, and Tsui because this is a known patient population to treat with teprotumumab, as taught by Ozzello.
Claims 112-113, 115-116, and 119-131 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 234 and 242 of copending Application No. 18/324,056, claims 41, 44, 49-52, and 56-57 of copending Application No. 19/233,919, claims 1 and 20 of copending Application No. 19/373,528, and claims 92 and 108-110 of copending Application No. 19/639,842 in view of Douglas et al., 2020 (instant PTO-892) and Tsui (EP2844289A1; instant PTO-892), as applied to claims 112-113, 115-116, 119-123, 125-127, and 129-130 above, claim 104 of copending Application No. 19/639,842, and further in view of Bittner et al., 2018 (instant PTO-892).
The teachings of copending Application Nos. 18/324,056, 19/373,528, 19/233,919, 19/639,842, Douglas, and Tsui are above. Further, claim 104 of 19/639,842 teaches that the antibody is administered subcutaneously.
However, copending Application Nos. 18/324,056, 19/373,528, 19/233,919, Douglas, and Tsui do not specifically teach that the antibody is administered to the subject subcutaneously.
Regarding claims 124, 128, and 131, Bittner teaches that subcutaneous delivery has become a valuable alternative to intravenous administration and that while pharmacokinetic profiles differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use [see Abstract].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have administered the antibody, as taught by the copending Applications, Douglas, and Tsui, subcutaneously. One would have been motivated to have administered the antibody subcutaneously because Bittner teaches that subcutaneous delivery has become a valuable alternative to intravenous administration and that while pharmacokinetic profiles differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and results in reduced drug delivery-related healthcare costs and resource use.
Examiner’s Note
Efforts were made to discover any pending application or granted US patent that claimed patentably distinct subject matter. However, it is also noted that the number of patent applications filed on this or related subject matter is significant. Applicant is in the best position to identity any other pending application or US patents that are directed to the instantly claimed method(s). Assistance in identifying such documents is appreciated.
Conclusion
No claims are allowed.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
