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
The amendments and remarks filed 06/27/2025 are acknowledged.
Claims 1-7, 9-10, 12-14, 16-28, 31-32, and 34 are pending.
Claims 1-2 , 9, 12, 16-19, 21-23, 27, and 34 are amended.
Claims 8, 11, 15, 29-30, 33, and 35 are cancelled.
Claims 5-7 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. The Examiner notes Applicant’s comment on page 9 of the remarks filed 06/27/2025 stating that “As to the election of species between rheumatoid arthritis, plaque psoriasis, psoriatic arthritis and ankylosing spondylitis, Applicant respectfully elects psoriatic arthritis, with traverse and reserves the right to file divisional applications in connection with all nonelected species. It is believed that a further species election was not required in view of the initial election of Crohn' s Disease.” No further species election was required, and as set forth in the Office Action mailed 12/20/2024, the election of species requirement between ulcerative colitis and Crohn’s disease for the TNFa-related disease is withdrawn. However, the election of species remains between the other diseases (i.e. rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis). Thus, the elected species for the TNFa-related disease remains as ulcerative colitis or Crohn’s disease.
Therefore, claims 1-4, 9-10, 12-14, 16-28, 31-32, and 34 are under examination.
Withdrawn
The rejections of claims 18, 21, 33, and 35 under 35 U.S.C. 112(b) are withdrawn. Applicant has amended claims 18 and 21 and canceled claims 33 and 35 to overcome the rejections.
The rejection of claim 11 under 35 U.S.C. 112(d) is withdrawn. Applicant has canceled the claim to overcome the rejection.
The rejection of claim 35 under 35 U.S.C. 101 is withdrawn. Applicant has canceled the claim to overcome the rejection.
The rejections of claims 1-3, 8-14, and 32-35 under 35 U.S.C. 102 are withdrawn. Applicant has amended claim 1 to require that the anti-TNFa antibody is infliximab and said patient has been intravenously administered with said anti-TNFa antibody or the antigen-binding fragment thereof, at least once prior to subcutaneous administration.
The previous rejections under 35 U.S.C. 103 are withdrawn in view of Applicant’s amendment to claim 1 requiring that the anti-TNFa antibody is infliximab and said patient has been intravenously administered with said anti-TNFa antibody or the antigen-binding fragment thereof, at least once prior to subcutaneous administration. However, new grounds of rejection are applied below.
The statutory double patenting rejections of claims 1-3, 8-9, 11-12, 15, 19, 22, and 26-35 over copending Application No. 18/774,066 are withdrawn. Applicant has amended claim 1 to overcome the rejections.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2). The Petition to Accept Color Drawings filed on 08/12/2021 was dismissed.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 recites the limitation “said patient has been intravenously administered with said anti-TNFa antibody or the antigen-binding fragment thereof, at least once, prior to subcutaneous administration.” The commas before and after “at least once” are grammatically awkward. The examiner suggests amending the claim to read as “said patient has been intravenously administered with said anti-TNFa antibody or the antigen-binding fragment thereof at least once prior to subcutaneous administration.” Appropriate correction is required.
New Grounds of Rejection Necessitated by AmendmentClaim 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
This rejection has been modified solely to address the amendment to claim 1
requiring that the anti-TNFa antibody is infliximab and said patient has been intravenously administered with said anti-TNFa antibody or the antigen-binding fragment thereof, at least once prior to subcutaneous administration.
Claims 1-3, 9-10, 12-14, 16-18, 22-26, 32, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Moodie (US 20180066048; 12/20/2024 PTO-892, as well as Moodie (WO 2016/162537)), in view of Wada et al., 1998 (12/20/2024 PTO-892) and Evans (WO2007019064; 12/20/2024 PTO-892).
The PGPub document (‘048) is the U.S. filing of PCT/EP2016/057847 from which the WO (‘537) document is the published version of. For the sake of convenience, the PGPub document will be referenced for the disclosure for which it is being relied upon for the rejections.
Regarding claims 1-3, 9-10, and 12, Moodie teaches a multiple-variable dose method for treating Crohn’s disease and ulcerative colitis, comprising administering to a subject in need thereof a first induction dose of an anti-TNFa antibody, such that a threshold level of TNFa inhibitor is achieved, and subsequently administering to the subject at least one treatment dose of the TNFa inhibitor, such that treatment occurs [0008]. Moodie further teaches that the antibody is administered subcutaneously [0029] and the treatment dose ranges from 20 to 160 mg [0468]. Moodie also teaches that the treatment dose is administered for a fixed period of time [0469] and is administered on a biweekly (every two weeks; at intervals of 2 weeks) dosing regimen, or on a monthly (every 4 weeks; at intervals of 4 weeks) dosing regimen [0473]. Moodie further teaches that an induction dose of the anti-TNFa antibody is administered prior to the treatment dose of the TNFa inhibitor [0008] and also teaches that the antibody can be administered intravenously [0858]. The Examiner is interpreting the induction dose as being a dose before treatment occurs. Moodie also teaches that the “induction phase” is equivalent to a loading phase (i.e. dose) comprising administering the TNFa inhibitor in order to attain a threshold level [0100]. Additionally, Moodie teaches that infliximab is a treatment for Crohn’s disease [0004 and 0903].
However, while Moodie does teach that the antibody can be administered intravenously, Moodie does not specifically teach that the induction dose (i.e. dose prior to treatment (subcutaneous dose)) is administered intravenously in a manner as required by 35 U.S.C. 103, and does not specifically teach that the anti-TNF antibody is infliximab.
Wada teaches that an intravenous loading dose is given to rapidly achieve a desired drug concentration in the blood [see Abstract].
Evans teaches neutralizing anti-TNFa antibodies that inhibit TNFa, specifically, infliximab, which has been approved for the treatment of Crohn’s disease [page 2, lines 29-33].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have specifically administered the induction dose (loading dose) of Moodie by intravenous administration, as taught by Wada. Since Moodie teaches that the induction dose is administered in order to attain a specific threshold level, one would have been motivated to administer the induction dose intravenously because Wada teaches that an intravenous loading dose rapidly achieves a desired drug concentration (i.e. a specific threshold). It further 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 anti-TNFa antibody of Moodie to specifically be infliximab, as taught by Evans. One would have been motivated to make this modification because Evans teaches that infliximab is an anti-TNFa antibody that is approved for the treatment of Crohn’s disease. It is prima facie obvious to substitute equivalents known for the same purpose (see MPEP 2144.06 (II)).
Claims 13 and 14 are included in this rejection because Moodie teaches that the TNFa antibody of the invention is used in combination with a drug used to treat Crohn’s disease, and that the drug can be azathioprine (immunosuppressant), methotrexate (DMARD) [0903], or topical corticosteroids [0917].
Claims 16 and 17 are included in this rejection because Moodie teaches that the method can comprise administration of a second induction dose [0023] and that any number of induction doses may be administered to achieve a threshold level of TNFa inhibitor (i.e. 2 times prior to subcutaneous administration (i.e. treatment dose) [0101].
Claim 18 is included in this rejection because Moodie teaches that the method of treating Crohn’s disease comprises administering a first induction dose, followed by a second induction dose two weeks later (administered at 0 and 2 weeks) [0034].
Claims 22 and 23 are included in this rejection because Moodie teaches that the treatment dose is administered 2 weeks (in 4 weeks) following the induction dose [0028].
Claims 24-26 are included in this rejection because the claims merely recite effects or results of administering the anti-TNFa antibody. Since the art anticipates the claim limitations of administering the anti-TNFa to treat Crohn’s disease at specific doses and intervals as described above, a person of ordinary skill in the art would have reasonably expected these effects to occur, absent evidence to the contrary.
Claim 32 is included in this rejection because Moodie teaches that the anti-TNFa antibody can be prefilled into a syringe [0884]. Since the syringe would be prefilled with the antibody, this would necessarily be before being administered to the patient.
Claim 34 is included in this rejection because Moodie teaches kits comprising an anti-TNFa antibody and administration instructions according to the multiple-variable dose method for treatment [0882], which Moodie teaches encompasses administering to the subject at a treatment dose of an anti-TNFa antibody, that the antibody is administered subcutaneously [0029] and the treatment dose ranges from 20 to 160 mg [0468]. MPEP 2112.01 (III) states “Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art” In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004).
Claims 1-4, 9-10, 12-14, 16-18, 22-26, 32, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Moodie (US 20180066048; 12/20/2024 PTO-892, as well as Moodie (WO 2016/162537)), in view of Wada et al., 1998 (12/20/2024 PTO-892) and Evans (WO2007019064; 12/20/2024 PTO-892), as applied to claims 1-3, 9-10, 12-14, 16-18, 22-26, 32, and 34 above, and further in view of ASCPT, 2016 (12/20/2024 PTO-892).
The teachings of Moodie, Wada, and Evans are above. Further, Moodie teaches that dosage regimens may be adjusted to provide the optimum desired response (e.g. a therapeutic or prophylactic response) and that the dose may be increased as indicated by the exigencies of the therapeutic situation [0881].
However, Moodie, Wada, and Evans do not specifically teach that the antibody is administered at an increased dose when the patient’s condition is not improved or therapeutic response is lost in a manner as required by 35 U.S.C. 102.
Regarding claim 4, ASCPT teaches that the common reaction to an insufficient response (condition is not improved or therapeutic response is lost) to a drug is to increase the dose administered [page 1, third paragraph].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have increased the dose of infliximab administered to the patient, as taught by Moodie, Wada, and Evans, if the patient’s condition is not improved or therapeutic response is lost, as taught by ASCPT. One would have been motivated to increase the antibody dose if the patient’s condition is not improved or therapeutic response is lost because ASCPT teaches that the common reaction to an insufficient response to a drug is to increase the dose administered and Moodie teaches that the dosage regimens may be adjusted to provide the optimum desired response and that the dose may be increased as indicated by the exigencies of the therapeutic situation (e.g. patient’s condition is not improved or therapeutic response is lost).
Claims 1-3, 9-10, 12-14, 16-26, 32, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Moodie (US 20180066048; 12/20/2024 PTO-892, as well as Moodie (WO 2016/162537)), in view of Wada et al., 1998 (12/20/2024 PTO-892) and Evans (WO2007019064; 12/20/2024 PTO-892), as applied to claims 1-3, 9-10, 12-14, 16-18, 22-26, 32, and 34 above, and further in view of Walpole et al., 2012 (12/20/2024 PTO-892).
The teachings of Moodie, Wada, and Evans are above. Moodie further teaches that the induction dose (intravenous administration) ranges from 161 to 320 mg [0008].
However, Moodie, Wada, and Evans do not specifically teach that the intravenous administration of the infliximab is at a dose of 1 to 10 mg/kg (as set forth in claim 19), 3 to 5 mg/kg (as set forth in claim 20), or 5 mg/kg in the patient with Chron’s disease (as set forth in claim 21).
Regarding claims 19-21, Walpole teaches that the average body mass globally is 62 kg [see page 3, right column, second paragraph].
Thus, a dose of 5 mg/kg to a patient with the average body mass of 62 kg would be 310 mg total.
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 Moodie, which teaches administering a dose of 161 to 320 mg, to specifically administer a dose at 5 mg/kg. One would have been motivated to make this modification because Walpole teaches that the average body mass globally is 62 kg, and so, administering a dose of 5 mg/kg to a patient with the average body mass of 62 kg would be a total dose of 310 mg (i.e. 5 mg/kg x 62 kg = 310 mg) which Moodie teaches is an acceptable dose for anti-TNFa antibodies (e.g. infliximab).
Claims 1-3, 9-10, 12-14, 16-18, 22-28, 32, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Moodie (US 20180066048; 12/20/2024 PTO-892, as well as Moodie (WO 2016/162537)), in view of Wada et al., 1998 (12/20/2024 PTO-892) and Evans (WO2007019064; 12/20/2024 PTO-892), as applied to claims 1-3, 9-10, 12-14, 16-18, 22-26, 32, and 34 above, and further in view of Rampton, 2001 (12/20/2024 PTO-892).
The teachings of Moodie, Wada, and Evans are above.
However, Moodie, Wada, and Evans do not specifically teach that the patient before subcutaneous administration has not responded to, is contraindicated from, or has intolerance to methotrexate, or that the patient has intolerance to 6-mercaptopurine and azathioprine.
Regarding claims 27 and 28, Rampton teaches that first line immunomodulatory therapy to initiate and maintain remission for patients with Crohn’s disease is usually azathioprine or 6-mercaptopurine, but that 20% of patients are resistant to or intolerant of thiopurines (having intolerance to 6-mercatopurin and azathioprine) [see page 1, left column, first paragraph]. Rampton further teaches that of patients with Crohn’s disease given methotrexate 25 mg/week intramuscularly with tapering of oral prednisolone for 16 weeks, 39% entered remission, of those given 15 mg/week intramuscularly for 40 weeks, 65% maintained remission, of those given 15 or 25 mg/week subcutaneously, 17% achieved remission, and of those given 15-22.5 mg/week methotrexate given orally in three divided doses for up to a year, 54% maintained remission [see page 1, left column, fifth paragraph-right column, first-second paragraphs]. Thus, since a percentage of the patient population with Crohn’s disease treated with methotrexate did not enter or maintain remission, this may indicate that some of the patients do not respond to, are contraindicated from, or have intolerance to methotrexate.
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 pharmaceutical composition of Moodie, Wada, and Evans comprising infliximab to the patient population with Crohn’s disease of Rampton that do not respond to, are contraindicated from, or have intolerance to methotrexate, or that have intolerance to 6-mercaptopurine and azathioprine. One would have been motivated to administer the composition of Moodie to the patient population of Rampton because Moodie and Evans teach that the composition can be used to treat Crohn’s disease and one would want to try to treat the disease with other therapeutics such as infliximab if the patient is not responding to current or previous therapeutics.
Claims 1-3, 9-10, 12-14, 16-18, 22-26, 32, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Moodie (US 20180066048; 12/20/2024 PTO-892, as well as Moodie (WO 2016/162537)), in view of Wada et al., 1998 (12/20/2024 PTO-892) and Evans (WO2007019064; 12/20/2024 PTO-892), as applied to claims 1-3, 9-10, 12-14, 16-18, 22-26, 32, and 34 above, and further in view of Krause (US 8,802,100; 12/20/2024 PTO-892).
The teachings of Moodie, Wada, and Evans are above. Moodie further teaches that the pharmaceutical composition comprises the anti-TNFa antibody and a pharmaceutically acceptable carrier, and it is preferable to include isotonic agents such as sorbitol in the composition, and may further comprise minor amounts of auxiliary substances such as wetting or emulsifying agents, preservatives, or buffers which enhance the shelf life or effectiveness of the anti-TNFa antibody [0857]. Moodie further teaches that the antibody can be incorporated into a formulation containing the antibody at a concentration of 75-125 mg/mL, 0.8-1.3 mg/ml of a surfactant (polysorbate 80), and less than 50 mg/ml of a polyol (sorbitol) [0872].
However, Moodie, Wada, and Evans do not specifically teach that the composition comprising the anti-TNFa antibody or antigen-binding fragment therefore comprises (B) 0.02 to 0.1% (w/v) of polysorbate; (C) 1 to 10% (w/v) of sorbitol; and (D) 1 to 50 mM of a buffer comprising acetate.
Regarding claim 31, Krause teaches pharmaceutical formulations with enhanced stability comprising anti-TNFa antibodies [column 3, lines 15-30] and that the pharmaceutical composition comprises between about 1-150 mg of antibody per ml of liquid formulation [column 13, lines 26-28]. Krause further teaches that a detergent is added to the formulation, such as a polysorbate, in an amount such that it reduces aggregation of the antibody, which can be between about 0.1-10 mg/ml, and in a preferred embodiment of about 0.1% of the formulation [column 14, lines 47-64]. Krause further teaches that a polyol is included in the formulation in an amount which may vary with respect to the desired isotonicity of the formulation, and can be sorbitol [column 14, lines 27-46]. Krause also teaches that the formulation is prepared comprising the antibody in a pH-buffered solution, the amount of buffer is dependent on the desired pH, and the buffer can be a buffer comprising acetate [column 13, lines 58 - column 14, lines 26].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to formulate the antibody taught by Moodie, Wada, and Evans (i.e. infliximab) in the pharmaceutical composition of Krause. One would have been motivated to use the pharmaceutical composition of Krause to have formulated a composition comprising the antibody, as taught by Moodie and Evans (i.e. infliximab) because Krause teaches that the formulation has enhanced stability comprising anti-TNFa antibodies. One of skill in the art would have a reasonable expectation that formulating the composition of Moodie and Evans (i.e. infliximab) in the composition of Krause would produce a composition with superior stabilization properties. It further would have been obvious to optimize the concentrations of the antibody, polysorbate, sorbitol, and buffer of the composition of Krause. One would have been motivated to optimize the composition to comprise 90-180 mg/ml of antibody, 0.02 to 0.1% of polysorbate, 1-10% of sorbitol, and 1-50 mM of buffer comprising acetate, because Krause teaches that these formulations are stable for antibody compositions, and specifically regarding the buffer and sorbitol, that the amount of buffer is dependent on the desired pH and the amount of polyol (sorbitol) may vary with respect to the desired isotonicity of the formulation. Further, MPEP 2144.05 (I) states “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facia case of obviousness exists.”
Additionally, regarding the specific concentrations for all the components of the composition (i.e. antibody, polysorbate, sorbitol, and buffer), these are art recognized variables and therefore, one would engage in routine optimization to obtain the desired result of a stable formulation for the composition, thus arriving at these specific concentrations as claimed. See MPEP 2144.05 (II). Further, it is the normal desire of scientists or artisans to improve upon what is already generally known. The MPEP states the following: generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller. 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson. 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc, v. Biocraft Laboratories Inc.. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert, denied, 493 U.S. 975 (1989); In re Kulling. 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler. 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). The determination of specific excipients at specific concentrations in the instant composition requires only routine experimentation for one of ordinary skill in the art. Therefore, given that the excipients and antibody are common to include in the formulation of antibody compositions, as taught in the art above, without specific evidence that the indicated concentrations are critical to the formulation, the identification of these properties will not render the subject matter patentable.
Maintained Rejections
Nonstatutory 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.
This rejection has been modified solely to address the amendment to claim 1
requiring that the anti-TNFa antibody is infliximab and said patient has been intravenously administered with said anti-TNFa antibody or the antigen-binding fragment thereof, at least once prior to subcutaneous administration.
Claims 1-3, 9-10, 12-14, 19, 22, 24-28, 31-32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-8, 11-21, 25-27, and 29 of copending Application No. 18/774,066 (‘066; reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1 of the instant application, claim 1 of ‘066 teaches a method for treatment of TNF-a-related disease, comprising a step of administering to a patient a pharmaceutical composition comprising an anti-TNFa antibody or its antigen binding fragment, wherein the anti-TNFa antibody or its antigen binding fragment is administered subcutaneously to the patient at a dose of 60 to 300 mg and at intervals of 1 to 8 weeks, claim 25 of ‘066 teaches that the anti-TNF-a antibody is infliximab, claim 14 of ‘066 teaches that wherein the patient is a patient who has been administered at least once intravenously with the anti-TNF-a antibody or its antigen-binding fragment before the subcutaneous administration.
Regarding claim 2 of the instant application, claim 2 of ‘066 teaches the method of claim 1, wherein the TNF-a-related disease is selected from the group consisting of rheumatoid arthritis, ulcerative colitis, Crohn's disease, plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis and claim 5 of ‘066 teaches the method of claim 2, wherein the TNF-a-related disease is selected from the group consisting of
ulcerative colitis, Crohn's disease, plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis.
Regarding claim 3 of the instant application, claim 7 of ‘066 teaches the method of claim 1, wherein the anti-TNF-a antibody or its antigen binding fragment is
administered to the patient at a dose of 80 to 100 mg, 110 to 130 mg, 170 to 190 mg, or 230 to 250 mg.
Regarding claim 9 of the instant application, claim 6 of ‘066 teaches the method of claim 5, wherein the anti-TNF-a antibody or its antigen binding fragment is administered to the patient at a dose of 120 to 240 mg.
Regarding claim 10 of the instant application, claim 8 of ‘066 teaches the method of claim 7, wherein the anti-TNF-a antibody or its antigen binding fragment is
administered to the patient at a dose of 90 mg, 120 mg, 180 mg or 240 mg.
Regarding claim 12 of the instant application, claim 11 of ‘066 teaches the method of claim 10, wherein the anti-TNF-a antibody or its antigen binding fragment is
administered to the patient at intervals of 2 or 4 weeks.
Regarding claim 13 of the instant application, claim 12 of ‘066 teaches the method of claim 1, wherein the anti-TNF-a antibody or its antigen binding fragment is co-administered with a disease-modifying anti rheumatic drug (DMARD).
Regarding claim 14 of the instant application, claim 13 of ‘066 teaches the method of claim 12, wherein the disease-modifying anti rheumatic drug (DMARD) is selected from the group consisting of methotrexate, leflunomide, sulfasalazine and hydroxychloroquine.
Regarding claim 19 of the instant application, claim 15 of ‘066 teaches the method of claim 14, wherein the patient is a patient who has been administered intravenously with the anti-TNF-a antibody or its antigen-binding fragment at a dose of 1 to 10 mg/kg for each administration.
Regarding claim 22 of the instant application, claim 16 of ‘066 teaches the method of claim 14, wherein the first subcutaneous administration is performed 2 to 8 weeks after the last intravenous administration.
Regarding claims 24 and 25 of the instant application, claim 17 of ‘066 teaches the method of claim 1, wherein the anti-TNF-a antibody or its antigen-binding fragment is maintained at a minimum blood concentration (Ctrough) of 3 to 16 μg/mL after it is administered subcutaneously to the patient, and claim 18 of ‘066 teaches the method of claim 1, wherein the anti-TNF-a antibody or its antigen-binding fragment is maintained at a minimum blood concentration (Ctrough) of 9 to 32 μg/mL after it is administered
subcutaneously to the patient.
Regarding claim 26 of the instant application, claim 19 of ‘066 teaches the method of claim 1, wherein the patient after the subcutaneous administration has one or more of the following characteristics: a) a decrease in DAS28 (Disease Activity Score in 28 joints) of at least 2.0; or b) a decrease in CDAI (Crohn's disease activity index) of at least 70.
Regarding claim 27 of the instant application, claim 20 of ‘066 teaches the method of claim 1, wherein the patient before the subcutaneous administration has one or more of the following characteristics: a) a patient who has an inadequate response to disease-modifying anti rheumatic drugs (DMARDs), including methotrexate; b) a patient who has not previously been treated with methotrexate and other DMARDs; c) a patient who exhibits elevated serologic indicators associated with severe axial-predominant
symptoms and inflammation, which show no proper response to common therapies; or
d) a patient who does not respond to, or is contraindicated to, or has intolerance to methotrexate, cyclosporine, or systemic therapies including psoralen ultraviolet A therapy (PUVA).
Regarding claim 28 of the instant application, claim 21 of ‘066 teaches the method of claim 1, wherein the patient before the subcutaneous administration has one or more of the following characteristics: a) a patient who has an inadequate response to, or has intolerance to, or is contraindicated for treatment with corticosteroids, 6-mercaptopurine, azathioprine or immunosuppressants; or b) a patient who does not respond to common therapies, including antibiotic, excretion or immunosuppressive therapies.
Regarding claim 31 of the instant application, claim 26 of ‘066 teaches the method of claim 1, wherein the composition comprising the anti-TNF-a antibody or its antigen binding fragment contains: (A) 90 to 180 mg/ml of the anti-TNFa antibody or its antibody binding fragment; (B) 0.02 to 0.1% (w/v) of polysorbate; (C) 1 to 10% (w/v) of sorbitol; and (D) 1 to 50 mM of a buffer comprising acetate.
Regarding claim 32 of the instant application, claim 27 of ‘066 teaches the method of claim 1, wherein the composition comprising the anti-TNF-a antibody or its antigen binding fragment is filled in a pre-filled syringe or an auto-injector before administration to the patient.
Regarding claim 34 of the instant application, claim 29 of ‘066 teaches a kit comprising: (a) a pharmaceutical composition comprising an anti-TNFa antibody or its antigen binding fragment; and (b) instructions that direct the pharmaceutical composition to be administered subcutaneously at a dose of 60 to 300 mg and at intervals of 1 to 8 weeks in order to treat a patient having TNFa-related disease, and claim 25 of ‘066 teaches that the anti-TNFa antibody is infliximab. MPEP 2112.01 (III) states “Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art” In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 9-10, 12-14, 19-28, 31-32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-8, 11-22, 25-27, and 29 of copending Application No. 18/774,066 (‘066; reference application).
The teachings of ‘066 are above. Further, regarding claims 20-21 of the instant application, claim 15 of ‘066 teaches the method according to claim 14, wherein the patient is a patient who has been intravenously administered with the anti-TNFa antibody or the antigen-binding fragment thereof at a dose of 1 to 10 mg/kg per administration, and regarding claim 23 of the instant application, claim 16 of ‘066 teaches the method according to claim 14, wherein the first subcutaneous administration is performed in 2 to 8 weeks after the last intravenous administration. However, ‘066 does not teach the limitations of the claims in a manner as required by 35 U.S.C. 102.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have selected any dosage within the range of 1 to 10 mg/kg, specifically 5 mg/kg as encompassed by claims 20 and 21, and to have selected a dosing schedule within the range of 2 to 8 weeks after the last intravenous administration, specifically 4 weeks as encompassed by claim 23. The art teaches that the antibody can be administered at a dose and at the dosing scheduled within the specific ranges, and therefore, there would be a reasonable expectation of success in picking any specific point within the ranges. Additionally, MPEP 2144.05 (I) states “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facia case of obviousness exists.”
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 9-10, 12-14, 19-28, 31-32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-8, 11-22, 25-27, and 29 of copending Application No. 18/774,066 (‘066; reference application), as applied to claims 1-3, 9-10, 12-14, 19-28, 31-32, and 34 above, in view of ASCPT, 2016 (12/30/2024 PTO-892).
The teachings of ‘066 are above.
However, ‘066 does not specifically teach that the antibody is administered at an increased dose when the patient’s condition is not improved or therapeutic response is lost.
Regarding claim 4, ASCPT teaches that the common reaction to an insufficient response (condition is not improved or therapeutic response is lost) to a drug is to increase the dose administered [page 1, third paragraph].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have increased the dose of antibody administered of ‘066 to the patient if the patient’s condition is not improved or therapeutic response is lost, as taught by ASCPT. One would have been motivated to increase the antibody dose if the patient’s condition is not improved or therapeutic response is lost because ASCPT teaches that the common reaction to an insufficient response to a drug is to increase the dose administered.
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 9-10, 12-14, 16-28, 31-32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-8, 11-22, 25-27, and 29 of copending Application No. 18/774,066 (‘066; reference application), as applied to claims 1-3, 9-10, 12-14, 19-28, 31-32, and 34 above, in view of Moodie (US 20180066048; 12/30/2024 PTO-892) and Wada et al., 1998 (12/30/2024 PTO-892).
The teachings of ‘066 are above. To reiterate, claim 14 of ‘066 teaches the method of claim 1, wherein the patient is a patient who has been administered at least once intravenously with the anti-TNF-a antibody or its antigen-binding fragment before the subcutaneous administration.
However, ‘066 does not specifically teach the patient is a patient who has been intravenously administered with the anti-TNFa antibody or the antigen-binding fragment thereof 2 or 3 times prior to subcutaneous administration, or that the patient is a patient who has been intravenously administered with the anti-TNFa antibody or the antigen-binding fragment thereof twice at Weeks 0 and 2.
Regarding claims 16-18, Moodie teaches a multiple-variable dose method for treating Crohn’s disease, comprising administering to a subject in need thereof a first induction dose of an anti-TNFa antibody, such that a threshold level of TNFa inhibitor is achieved, and subsequently administering to the subject at least one treatment dose of the TNFa inhibitor, such that treatment occurs [0008]. Moodie further teaches that the antibody is administered subcutaneously [0029] and the treatment dose ranges from 20 to 160 mg [0468]. Moodie also teaches that the treatment dose is administered for a fixed period of time [0469] and is administered on a biweekly (every two weeks; at intervals of 2 weeks) dosing regimen, or on a monthly (every 4 weeks; at intervals of 4 weeks) dosing regimen [0473]. Further, Moodie teaches that an induction dose of the anti-TNFa antibody is administered prior to the treatment dose of the TNFa inhibitor [0008] and also teaches that the antibody can be administered intravenously [0858]. The Examiner is interpreting the induction dose as being a dose before treatment occurs. Moodie also teaches that the “induction phase” is equivalent to a loading phase (i.e. dose) comprising administering the TNFa inhibitor in order to attain a threshold level [0100]. Moodie further teaches that the method can comprise administration of a second induction dose [0023] and that any number of induction doses may be administered to achieve a threshold level of TNFa inhibitor (i.e. 2 times prior to subcutaneous administration (i.e. treatment dose) [0101]. Moodie also teaches that the method of treating Crohn’s disease comprises administering a first induction dose, followed by a second induction dose two weeks later (administered twice at 0 and 2 weeks) [0034].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have specifically administered an induction dose (intravenous administration) of the pharmaceutical composition comprising an anti-TNFa antibody (i.e. infliximab) of ‘066 two times prior to subcutaneous administration at Weeks 0 and 2, as taught by Moodie. One would have been motivated to make this modification because Moodie teaches that this is a known dosing regimen for anti-TNFa antibodies, and therefore would have a reasonable expectation of success.
Further, to the extent claim 34 is not taught by ‘066, Moodie teaches kits comprising an anti-TNFa antibody and administration instructions according to the multiple-variable dose method for treatment [0882]. Therefore, it further 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 pharmaceutical composition comprising an anti-TNFa antibody or its antigen binding fragment, wherein the anti-TNFa antibody is infliximab, as taught by ‘066, to be in a kit with instructions for dosing, as taught by Moodie. One would have been motivated to make this modification because Moodie teaches putting anti-TNFa antibodies into a kit with administration instructions. MPEP 2112.01 (III) states “Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art” In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004).
This is a provisional nonstatutory double patenting rejection.
Claims 1-3, 9-10, 12-14, 19, 22, 24-28, and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 12-17, 20-21, and 27 of copending Application No. 16/643,377 (‘377; reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1-3, 9-10, and 12 of the instant application, claim 1 ‘377 teaches a method for treatment of Inflammatory Bowel Disease comprising a step of administering to a patient a pharmaceutical composition comprising infliximab or its antigen binding fragment, a surfactant, a sugar or a derivative thereof, and a buffer, wherein the pharmaceutical composition is administered subcutaneously to the patient at a dose of 120 mg, and at an interval of 2 weeks, claim 5 of ‘377 teaches the method of claim 1, wherein said inflammatory bowel disease is selected from the group consisting of ulcerative colitis and Crohn’s disease (TNFa-related diseases), and claim 14 teaches the method of claim 1, wherein the patient has been administered at
least once intravenously with the anti-TNF-a antibody or its antigen-binding fragment before the subcutaneous administration.
Regarding claim 13 of the instant application, claim 12 of ‘377 teaches the method of claim 1, wherein the anti-TNF-a antibody or its antigen binding fragment is co-administered with a disease-modifying anti rheumatic drug (DMARD).
Regarding claim 14 of the instant application, claim 13 of ‘377 teaches the method of claim 12, wherein the disease-modifying anti rheumatic drug (DMARD) is selected from the group consisting of methotrexate, leflunomide, sulfasalazine and hydroxychloroquine.
Regarding claim 19 of the instant application, claim 15 of ‘377 teaches the method of claim 14, wherein the patient who has been administered intravenously with the anti-TNF-a antibody or its antigen-binding fragment is administered a dose of 1 to 10 mg/kg for each administration.
Regarding claim 22 of the instant application, claim 16 of ‘377 teaches the method of claim 14, wherein the first subcutaneous administration is performed 2 to 8 weeks after the last intravenous administration.
Regarding claims 24 and 25 of the instant application, claim 17 of ‘377 teaches the method of claim 1, wherein the anti-TNF-a antibody or its antigen binding fragment is maintained at a minimum blood concentration (Ctrough) of 3 to 16 μg/mL after it is administered subcutaneously to the patient.
Regarding claim 26, the claim merely recites effects or results of administering the anti-TNFa antibody. Since the art anticipates the claim limitations of administering the anti-TNFa to treat Crohn’s disease at specific doses and intervals as described above, a person of ordinary skill in the art would have reasonably expected these effects to occur, absent evidence to the contrary.
Regarding claim 27 of the instant application, claim 20 of ‘377 teaches the method of claim 1, wherein the patient before the subcutaneous administration has one or more of the following characteristics: a) a patient who has an inadequate response to disease-modifying anti rheumatic drugs (DMARDs), including methotrexate; b) a patient who has not previously been treated with methotrexate and other DMARDs; c) a patient who exhibits elevated serologic indicators associated with severe axial-predominant
symptoms and inflammation, which show no proper response to common therapies; or d) a patient who does not respond to, or is contraindicated to, or has intolerance to methotrexate, cyclosporine, or systemic therapies including psoralen ultraviolet A therapy (PUVA).
Regarding claim 28 of the instant application, claim 21 of ‘377 teaches the method of claim 1, wherein the patient before the subcutaneous administration has an inadequate response to, or has intolerance to, or is contraindicated for treatment with corticosteroids, 6-mercaptopurine, azathioprine or immunosuppressants.
Regarding claim 32 of the instant application, claim 27 of ‘377 teaches the method of claim 1, wherein the composition is filled in a pre-filled syringe or an auto-injector before administration to the patient.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-3, 9-10, 12-14, 19-23, 24-28, and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 12-17, 20-21, and 27 of copending Application No. 16/643,377 (‘377; reference application).
The teachings of ‘377 are above. Further, regarding claims 20-21 of the instant application, claim 15 of ‘377 te