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 .
DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of species: a combination of intravenous and subcutaneous and SEQ ID NOs: 7-10 and 13 in the reply filed 02/20/2025 is acknowledged. The traversal is on the ground(s) that there would not be undue burden to search the entire scope of the species. This is not found persuasive because search burden is not in consideration for lack of unity.
Claims 14, 17, 19-22 and 27 are now under consideration in the instant Office Action.
The requirement is still deemed proper and is therefore made FINAL.
Withdrawn Objections
Objections to claim 23 due to minor informalities are hereby withdrawn in view of the cancellation of the claim.
Withdrawn Rejections
Rejections of claims 14-22 and 27 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement are hereby withdrawn in view of amendments to the claims.
Modified Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 102
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 –
(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.
Claims 14, 19-21 and 27 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Heusser et al. (US 2014/341,898 A1, in IDS filed 01/31/2022).
Heusser teaches the use of “silent Fc variants of anti-CD40 antibodies and compositions and methods of use of said antibodies for treating pathological disorders such as autoimmune and inflammatory disorders”, see Abstract. This silenced antibody is a “fully humanized, non-agonist anti-CD40 antibody (IgG1, kappa) that blocks CD154 (also known as CD40 ligand; CD40L)-mediated leukocyte activation and can mediate antibody-dependent cellular cytotoxicity (ADCC) of human leukocytes and B cell lymphomas in vitro”, see paragraph 0005, and is “predicted to have an improved safety profile relative to the parental anti-CD40 antibodies, and in particular may be more suitable for non-oncologic indications, such as autoimmune diseases”, see paragraph 0006.
This silenced anti-CD40 antibody is comprised within the reference’s SEQ ID NOs: 7 and 8 as the heavy and light chain variable region sequences, which are 100% matches for the instant SEQ ID NOs: 7 and 8. Instant SEQ ID NO: 7 comprises the HCDRs SEQ ID NOs: 1-3 and instant SEQ ID NO: 8 comprises the LCDRs SEQ ID NOs: 4-6, which are also matches for the corresponding CDR sequences. The antibody referred to as “CFZ533” comprises instant SEQ ID NOs: 7-8 and therefore is taught by the reference. Heusser also discloses that the “antagonist anti-CD40 antibodies or proteins described herein, for example mAb1, mAb2 or mAb3, can be used in accordance with the methods of the invention to treat autoimmune and/or inflammatory disorders including, but not limited to, … Type I and Type II diabetes, …”, see paragraph 0143.
Heusser teaches that the pharmaceutical composition is formulated to be compatible with the following routes of administration: parenteral, (e.g., intravenous (IV), intramuscular (IM), intradermal, subcutaneous (SC), or infusion), oral and pulmonary (e.g., inhalation), nasal, transdermal (topical), transmucosal, and rectal administration, see paragraph 0169.
In regards to the dosage, Heusser teaches various doses and dosage intervals that fall within the scope of instant claims 14, 17, 19-22 and 27 in paragraphs 0171-0179. In paragraph 0172, Heusser discloses various doses that can be scaled to a patient’s body weight, with dosages ranging from 0.01 mg/kg, 0.03 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg, 2 mg/kg, 2.5 mg/kg, 3 mg/kg, 5 mg/kg, 7 mg/kg, 10 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, 40 mg/kg, 45 mg/kg, to 50 mg/kg. This reads on instant claim 14 wherein the initial dosage is 30 mg/kg. These dosages are to be administered as needed, with the “method comprising administration of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, or more therapeutically effective doses of a pharmaceutical composition comprising an antagonist anti-CD40 antibody or fragment thereof. The frequency and duration of administration of multiple doses of the pharmaceutical compositions comprising anti-CD40 antibody or protein can be readily determined by one of skill in the art”, see paragraph 0173. This reads on instant claims 19-20 wherein the maintenance dosage for patients in categories I-III ranges from 100 mg to 350 mg based on their weight when administered at a dosage in the range of 4.5 mg/kg to 7 mg/kg.
Paragraphs 0174-0179 further discuss the dosing regimen regarding the first administration and subsequent administrations tailored to a patient’s specific needs over the course of a treatment period, beginning with an initial intravenous loading dose from about 20 mg/kg to about 50 mg/kg followed by a weekly dosing schedule administered subcutaneously under the purview of maintenance of a particular disease state. Additionally, Heusser teaches that the dosing regimen can be scaled by one skilled in the art to achieve a particular disease state, such as one claimed in instant claim 27, given the information in the disclosure.
Therefore, claims 14, 19-21, and 27 are anticipated by Heusser et al.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 14, 17, 19-22, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over by Heusser et al. (US 2014/341,898 A1, in IDS filed 01/31/2022), in view of Al-Fifi 2010 (in instant PTO-892).
The relevance of Heusser et al. is discussed above.
However, Heusser et al. does not teach a pediatric patient population diagnosed with Type 1 Diabetes. Al-Fifi remedies this deficiency.
Al-Fifi teaches the incidence of type 1 diabetes in pediatric populations. Al-Fifi teaches “most commonly, it presents in childhood, but one-fourth of all cases are diagnosed in adults. Type 1 diabetes accounts for approximately two-thirds of the newly diagnosed cases in patients ≥19 years of age”, see Introduction. Al-Fifi discloses that there is a peak in diagnosis of type 1diabetes at 4 to 6 years of age, see Introduction.
It would be obvious at the time of the instant invention to use the anti-CD40 antibody dosage assigned by body weight taught by Heusser et al., which is an immunotherapeutic therapy that results in the treatment of autoimmune conditions such as type 1 diabetes, with the diagnosis age range taught by Al-Fifi which shows that a target population for type 1 diabetes treatment is pediatric populations. Heusser teaches dosages for a wide range of body weights, including lower body weights which includes pediatric patients. While Heusser et al. does not explicitly recite pediatric populations but does recite dosages that are inclusive of patients in the pediatric weight range, it is inherent through the disclosure of Al-Fifi that children are included in the population of patients affected by type 1 diabetes mellitus and in need of treatment. One would be motivated to combine the dosage regimen with the knowledge of the incidence rate of type 1 diabetes in pediatric populations with the expectation of treating the disease.
Therefore, claims 14, 17, 19-22, and 27 are rejected as obvious over Heusser et al. and Al-Fifi.
.
Response to Arguments
Applicant's arguments filed 08/11/2025 have been fully considered but they are not persuasive.
Applicant argues “Heusser generally teaches treatments of various disease and conditions at various dose amounts with various dose regimens. Accordingly, a person of skill in the art would not find that Heusser explicitly or implicitly discloses the combination of each of the features of claim 14, such as treatment of T1DM in a human by administering CFZ533 with an intravenous loading dose of 30 mg/kg at day 1 and a once weekly subcutaneous maintained dose between 100 mg and 350 mg starting at day 8.” This is not found persuasive.
The prior art rejection above teaches the appropriate ranges for administering the antibody of the instant claims. Heusser teaches that the “antagonist anti-CD40 antibodies or proteins described herein, for example mAb1, mAb2 or mAb3, can be used in accordance with the methods of the invention to treat autoimmune and/or inflammatory disorders including, but not limited to, … Type I and Type II diabetes, …”, see paragraph 0143, and the instantly claimed antibody is a 100% match for the one used by Heusser. As such, Heusser provides a targeted approach to treating a specific disease, Type I diabetes, with a broad range of dosages disclosed so that treatment can be tailored to an approximate goal. One of ordinary skill in the art would be able to optimize the dosage as necessary to achieve the desired result, with the intravenous loading dose of 30 mg/kg at day 1 and once weekly subcutaneous maintained dose between 100 mg and 350 mg starting at day 8 falling well within the range that was experimentally determined by Heusser to be safe and effective to try on patient populations. Paragraphs 0174-0179 of Heusser further discuss the dosing regimen regarding the first administration and subsequent administrations tailored to a patient’s specific needs over the course of a treatment period, beginning with an initial intravenous loading dose from about 20 mg/kg to about 50 mg/kg followed by a weekly dosing schedule administered subcutaneously under the purview of maintenance of a particular disease state. Additionally, Heusser teaches that the dosing regimen can be scaled by one skilled in the art to achieve a particular disease state, such as one claimed in instant claim 27, given the information in the disclosure.
Applicant argues that the instantly claimed antibody used at the claimed dosages resulted in unexpected results. This is not found persuasive.
As discussed above, the antibody of the instant claims and dosages are anticipated by Heusser. As such, one of ordinary skill in the art would find it routine and obvious to obtain the results as depicted in Exhibit A and Figures 1B-D of the Remarks given that they are the same conditions and limitations as taught in the prior art.
Therefore, the rejections are maintained as being anticipated by Heusser.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SELAM BERHANE whose telephone number is (571)272-6138. The examiner can normally be reached Monday - Friday, 9-5.
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/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675