CTNF 18/569,346 CTNF 81188 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claim Status Claims 1-20 are currently pending. Claims 1-20 are being examined in this application. Priority This application is filed under 35 U.S.C 371 of PCT/IB2022/055485 (filed on 6/14/2022), which claims priority to PCT/IB2021/055217 (6/14/2021). Information Disclosure Statement The IDS filed on 1/22/2024 has been considered. See the attached PTO 1449 forms. Claim Rejections - 35 USC § 112 07-30-02 AIA 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. 07-34-01 Claim(s) 1, 3 and 20 is/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. 07-34-10 AIA Regarding claim s 1 and 20 , the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Regarding claim 3 : A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 3 recites the broad recitation of “about 5 to about 30 mPa-s”, and the claim also recites “5 to about 20 mPa-s” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. 07-12-aia AIA (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Liu et al Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1)/(a/2) as anticipated by Liu et al . ( US20020045571; 4/18/2002; or filed earlier ). The instant claims recite “ A stable aqueous pharmaceutical composition comprising at least 50 mg/ml to about 150 mg/ml of an anti-IgE antibody, such as ligelizumab, about 200-300 mM trehalose, about 5-25 mM histidine, and about 0.01 % to 0.05% polysorbate 20 (w/v), wherein the pH of the composition is from about 4.7 to about 5.2 .” Liu et al , throughout the reference, teach compositions comprising anti-IgE antibodies in various formulation and the method of use thereof (e.g. Abstract; claims). For Claim 1: The reference teaches anti-IgE antibody composition comprising various amounts of anti-IgE antibody (such as rHuMAb E25) including 40mg/ml (e.g. [0023]) and 94mg/ml (e.g. para [0027]), and “ at least 80mg/ml ” of protein that is an anti-IgE antibody (e.g. claims 1, 24-28). The reference teaches including a sugar including trehalose in the composition in various amounts that can range from 60-300 mM (e.g. Claims 1, 16-18). The reference also teaches inclusion of histidine as a buffer in various amounts (e.g. claims 45-50) such as 5 mM, 16mM , etc (e.g. [0012]; [0021]; [0166]; [0169]). The reference also teaches inclusion of a surfactant such as polysorbate 20 in the antibody composition in various amounts ranging from 0.001-0.5% or 0.005-0.05% (e.g. [0138]; [0162]; [0164]). The reference also teaches that the antibody composition can have various pH such as about 4.0 to about 5.3 (pH=4.7 or 5.2) for the purpose of reduced viscosity (e.g. [0012]; Claim 45; [0169]). Liu WO Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1)/(a/2) as anticipated by Liu et al . ( WO2004091658; 10/28/2004; filed on 3/29/2004 or earlier; hereinafter referred to as Liu WO; cited in IDS ). The instant claims recite “ A stable aqueous pharmaceutical composition comprising at least 50 mg/ml to about 150 mg/ml of an anti-IgE antibody, such as ligelizumab, about 200-300 mM trehalose, about 5-25 mM histidine, and about 0.01 % to 0.05% polysorbate 20 (w/v), wherein the pH of the composition is from about 4.7 to about 5.2 .” Liu et al , throughout the reference, teach compositions comprising anti-IgE antibodies in various formulation and the method of use thereof (e.g. Abstract; claims). For Claim 1: The reference teaches anti-IgE antibody composition comprising various amounts of anti-IgE ranging from 100-260 mg/ml (e.g. claims 1-16). The reference teaches including a sugar including trehalose in the composition in various amounts that can range from 20-350 mM (e.g. p.3, ll.1+) and exemplified amount of 192 mM (e.g. p.4, lines 18+). The reference also teaches inclusion of histidine as a buffer in various amounts ranging from 10-100mM such as 20mM , etc (e.g. p.2, lines 23+; p.5, lines 1+; ). The reference also teaches inclusion of a surfactant such as polysorbate 20 in the antibody composition in various amounts ranging from 0.01-0.1% (e.g. p.2, line 25; p.67, top page; p.69, Example 4). The reference also teaches that the antibody composition can have various pH such as about 4.0 to about 5.3 for the purpose of reducing viscosity (e.g. p.2, lines 11+), and pH of 5.5-7.0 (e.g. p.2, ll.25+). Claim Rejections - 35 USC § 103 07-20-aia AIA 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. Liu et al, Liu WO and Maurer et al 07-21-aia AIA Claim (s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al ., ( US20020045571; 4/18/2002 ) , in view of Liu WO ( WO2004091658; 10/28/2004; filed on 3/29/2004 or earlier; hereinafter referred to as Liu WO), and Mauer et al ., (Ligelizumab for Chronic Spontaneous Urticaria. The New England Journal of Medicine. Vol.381(14): 1321-1332; 10/3/2019) . Liu et al , throughout the reference, teach compositions comprising anti-IgE antibodies in various formulation and the method of use thereof (e.g. Abstract; claims), as discussed supra. For Claim 3 : The reference also teaches the antibody composition can have various viscosities depending on the buffer used (e.g. [0071]; [0072]; [0012]). As discussed above, the Liu reference teaches compositions with the same components (buffer, sugar, etc) in the same amounts as the instant claimed compositions, then the compositions of the Liu reference would necessarily have the same viscosities as claimed, as evidenced by the instant claims and specification. For Claim 4 : The reference also teaches that the antibody composition can have various pH such as about 4.0 to about 5.3 (pH=4.7, 5.0 or 5.2) for the purpose of reduced viscosity (e.g. [0012]; Claim 45; [0169]). For Claims 5-6 : The reference also teaches inclusion of a surfactant such as polysorbate 20 in the antibody composition in various amounts ranging from 0.001-0.5% or 0.005-0.05% and examples with 0.01% or 0.03% (e.g. [0138]; [0162]; [0164]), which reads on the about 0.01-0.2%. The reference’s teaching renders obvious the instant claimed amount of polysorbate 20 because it is within skilled in the art to optimize the amount of the surfactant for the purpose of stabilizing the antibody composition as taught by the Liu reference. For Claims 7-8 : The reference also teaches inclusion of histidine as a buffer in various amounts (e.g. claims 45-50) such as 5 mM, 16mM , 10mM , 20mM etc (e.g. [0012]; [0021]; [0162]; [0166]; [0169]). For Claims 9-10 : The reference teaches including a sugar including trehalose in the composition in various amounts that can range from 60-300 mM (e.g. Claims 1, 16-18). The reference also teaches the sugar are added as lyoprotectant that can be added according to the amount of the antibody (e.g. [0136]; [0137]). For Claims 11-12 : The reference teaches anti-IgE antibody composition comprising various amounts of anti-IgE antibody (such as rHuMAb E25) including 40mg/ml (e.g. [0023]) and 94mg/ml (e.g. para [0027]), and “ at least 80mg/ml ” of protein that is an anti-IgE antibody (e.g. claims 1, 24-28). For Claim 13 : The Liu reference teaches using aqueous solution as buffer (e.g. [0064]; [0168]). The reference teaches anti-IgE antibody composition comprising various amounts of anti-IgE antibody such as “at least 80mg/ml” of protein that is an anti-IgE antibody (e.g. claims 1, 24-28), and “ 125 mg/ml ” of an anti-IgE antibody (e.g. [0022]). The reference teaches including a sugar including trehalose in the composition in various amounts that can range from 60-300 mM (e.g. Claims 1, 16-18) and an example amount of 250 mM (e.g. [0169]). The reference also teaches inclusion of histidine as a buffer in various amounts (e.g. claims 45-50) such as 5 mM, 16mM, 20mM etc (e.g. [0012]; [0021]; [0166]; [0169]). The reference also teaches inclusion of a surfactant such as polysorbate 20 in the antibody composition in various amounts ranging from 0.001-0.5% or 0.005-0.05% (e.g. [0138]; [0162]; [0164]), and examples with 0.01% or 0.03% (e.g. [0138]; [0162]; [0164]), which reads on the about 0.01-0.02%. The reference’s teaching renders obvious the instant claimed amount of polysorbate 20 since 0.02% is in between 0.01 and 0.03%. It would have been obvious for one of skilled in the art to optimize the amount of histidine buffer to achieve the desired pH level for adjusting the viscosity of the composition as taught by Liu. The reference also teaches that the antibody composition can have various pH such as about 4.0 to about 5.3 (pH=4.7, 5.0 or 5.2) for the purpose of reduced viscosity (e.g. [0012]; Claim 45; [0169]). For Claim 14 : The Liu reference teaches the same components in the same amounts for the anti-IgE antibody composition as the instant claims, and thus would possess the same inherent property of stability, as evidenced by the instant specification and claims. For Claims 15-16 : The reference teaches administration of the antibody composition (e.g. claim 30; [0144]; [0147]+) for the purpose of treating allergic diseases (e.g. [0152]). For Claim 17 : The reference teaches formulating various dosages (e.g. [0150]) including aqueous dosage formulation (e.g. [0145]; [0168]; [0064]). For Claims 18-19 : The reference teaches syringe containing the antibody composition (e.g. [0154]). The Liu reference does not explicitly teach the anti-IgE antibody is ligelizumab as recited in claims 2 and 13 . The Liu reference also does not explicitly teach the automated delivery device as recited in claim 20 . However, Maurer et al ., throughout the reference, teach using Ligelizumab for treating allergy related disease (e.g. Abstract). The Maurer reference teaches Ligelizumab is a humanized monoclonal anti-IgE antibody (e.g. Abstract; p.1322, left col.). The reference teaches Ligelizumab is a “new high-affinity humanized monoclonal anti-IgE antibody that has previously shown dose-dependent and time dependent suppression of free IgE…” (p.1322, left col., last para.), which IgE is known to be involved in autoimmune mechanism of patients with various allergy/autoimmune diseases. The reference also teaches administer the antibody to patients for treatment of Spontaneous Urticaria (e.g. p.1322+). In addition. the Liu WO reference, throughout the reference, teach composition of anti-IgE antibody and uses thereof, as discussed supra. The Liu WO reference also teaches using autoinjector to administer antibody composition (e.g. Claims 22-25; pp.61-62). Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the IgE antibody composition (or method of using thereof) of Liu et al to include the Ligelizumab (an IgE antibody) of Maurer et al for the purpose of treating allergy/autoimmune disease, because both of the Liu and Maurer references teach anti-IgE antibodies formulation for treating patients that involve IgE. In addition, because both the Liu and Maurer references teach formulation and method of treatment using different anti-IgE antibodies, it would have been obvious to one skilled in the art to substitute one type of anti-IgE antibody for another to achieve the predictable result of inhibiting IgE in patients in need thereof. Since the Maurer reference teaches the advantage of the Ligelizumab antibody that is humanized and has high affinity for IgE, one of skilled in the art would be highly motivated to improve the anti-IgE treatment formulation with the Ligelizumab antibody using the known formulation of buffer, sugar, and other ingredients as taught by Liu et al. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the IgE antibody composition delivery mechanism/apparatus of Liu et al and Maurer to include the autoinjector of Liu WO for the purpose improve delivery efficiency, because all cited references teach anti-IgE antibodies formulation for treating patients that involve IgE, and using various method/apparatus for administration/delivery. A person of ordinary skill in the art would have reasonable expectation of success of achieving such modifications since all the cited references have demonstrated various formulations and method of using/administering/delivering anti-IgE antibodies. Conclusion and Correspondence No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUE LIU whose telephone number is (571)272-5539. The examiner can normally be reached M-F 9-5. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor (director), Jennifer Michener can be reached at 571-272-1424. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /SUE X LIU/Supervisory Patent Examiner, Art Unit 1616 Application/Control Number: 18/569,346 Page 2 Art Unit: 1616 Application/Control Number: 18/569,346 Page 3 Art Unit: 1616 Application/Control Number: 18/569,346 Page 4 Art Unit: 1616 Application/Control Number: 18/569,346 Page 5 Art Unit: 1616 Application/Control Number: 18/569,346 Page 6 Art Unit: 1616 Application/Control Number: 18/569,346 Page 7 Art Unit: 1616 Application/Control Number: 18/569,346 Page 8 Art Unit: 1616 Application/Control Number: 18/569,346 Page 9 Art Unit: 1616 Application/Control Number: 18/569,346 Page 10 Art Unit: 1616 Application/Control Number: 18/569,346 Page 11 Art Unit: 1616 Application/Control Number: 18/569,346 Page 12 Art Unit: 1616
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