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 Status of the Claims 1. Claims 1-59 are the original claims filed 11/21/2022. In the Preliminary Amendment of 6/16/2023, Claims 6, 8-9, 11, 13-14, 16-17, 19, 21-25, 27, 29-32, 34-36, 40, 42-45, 47-48, 54, and 56-58 are amended and claims 1-4, 46, and 49-52 are canceled. Claims 5-45, 47-48 and 53-59 are the clams. Priority 2. USAN 17 / 999 , 477 , filed 11/21/2022 , is a National Stage entry of PCT/CA2021 /050691, International Filing Date: 05/20/2021 , PCT/CA2021/050691 Claims Priority from Provisional Application 63 / 027 , 569, filed 05/20/2020 , PCT/CA2021/050691 Claims Priority from Provisional Application 63 / 163 , 686, filed 03/19/2021. Information Disclosure Statement 3. As of 11/18/2025 , a total of five ( 5 ) IDS are filed: 11/21/2022; 7/11/2024; 7/26/2024 ; 9/5/2025; and 10/24/2025 . The corresponding initialed and dated 1449 form is considered and of record. Objections Specification 4. The disclosure is objected to because of the following informalities: a) The use of the term Uniprot, Sepharose, Tween, Tris , BiaCore, GraphPad , MassHunter , Supelco , Chemstation , which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term . Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required. b) The figure legend to Figure 3 is objected to for failing to include the sequence identifier for the peptides > 4 amino acids in length. Pursuant to 37 CFR 1.821-1.825 the SEQ ID NO is required. c) [00138] is objected to for failing to include the sequence identifier for the peptides > 4 amino acids in length for 6xHis. Pursuant to 37 CFR 1.821-1.825 the SEQ ID NO is required. Claim Objections 5. Claim s 5-45, 47-48 and 53-59 are objected to because of the following informalities: a ) Claims 5-45, 47-48 and 53-59 are indefinite, confusing and ambiguous. The preamble of claim 5 recites “ from one to three stability-enhancing amino acid mutations ” whilst the body of the claim 5 recites: “ (a) one or more mutation selected from: ” “ (b) two or more mutations selected from: ” “ (c) three or more mutations comprising: ” and “ wherein the Fc variant has an increased CH2 domain melting temperature (Tm) as compared to a parental Fc that does not include the one or more stability-enhancing amino acid mutations .” The range of mutations for elements (a)-(c) and the “wherein” clause exceed the scope of the range (from one to three) defined in the preamble. The POSA cannot reasonably ascertain the metes and bounds of the claimed invention. It is not apparent how the limitation in the preamble can be a non-limiting descriptive phrase. MPEP 2111. b) Claims 23-24 are objected to for the use of symbols, e.g., 242C_336C and 287F/428F . Clarification is requested. Appropriate correction is required. Claim Rejections - 35 USC § 112 The following is a quotation of 35 U.S.C. 112(b): (b ) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the appl icant regards as his invention. 6. Claims 5-45, 47-48 and 53-59 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. a) Claims 5-45, 47-48 and 53-59 are indefinite in Claim 5 for reciting a m u tation at position 287, where t he mutation is a substitution a t the amin o acid at position 287 with His. Figure 3A shows that A287 aligns wit h H in the correspo nding position of the CH 3 domain of IgE . Si milarly, the reference to a m uta t ion at po sition 308, where the mu tation is a substitution of the amino acid at position 308 with Ile is unclear . Figure 3A shows that V 3 08 aligns with I in the corresponding position of the CH3 domain of IgM . The claims encompass IgE and IgM (cl aims 25-26 ), and it is unclear what subs tit ution is contemplated at posit ion 287 in IgE and position 308 in IgM. Paragraph [ 0050] indicates that while the amino acid numbering used herein relates to an IgG Fc , the POSA could read ily determine the equivalent positions for the mutations in other Ig Fc sequences by s equence alignment using are of a number of sequence alignment to ols in art. The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Written Description 7 . Claim s 32-33 and 54-55 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims 32-33 and 54-55 are drawn to infinite Tm ranges reciting “at least __ ºC.” The specification provides no practical or actual support for the ranges. (MPEP 706.03(m) states in part "New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 to § 608.04(c). See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976) and MPEP § 2163.05 for guidance in determining whether the addition of specific percentages or compounds after a broader original disclosure constitutes new matter.”) 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. 8. Claim (s) 5- 20, 23- 45, 47-48 and 53-59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lowman (WO 2006031370; 3/23/2006; IDS 11/21/2022 ) in view of Ruker ( WO 2012032080 ; 3/15/2012 (IDS 11/21/2022 ), Hinton (US 8624007; 1/7/2014 ; IDS 11/21/2022 ), Liu (US 2014/0112926 ; IDS 11/21/2022 ) and Reyes ( US 2012/0100140; 4/26/2012; IDS 11/21/2022 ) . The species limitation for “a pair of mutations at position 242 and 336 which are both substitutions with Cys” is not covered by this rejection. AS regards the claims that encompass a Fc mutation selected from position 250, 287, 308, 309 and 428 : Lowman teaches Fc mutations at 250, 287, 308, 309 and 428 in Table 1: Lowman teaches A287H in Table 6, page 64 where the mutation is associated with increased FcRn binding. As regards the claims that encompass a Fc mutation selected from position 250 : Ruker teaches stability engineered human IgG Fc mutant by engineering at least one of the point mutations as listed in Table 1 as for example, 250 Ile (I) and 250 Val (V); Ruker teaches “ The preferred Fc mutant has a Tm value, which is higher than the wild type. For the purpose of the invention, the increase of any individual Tm value regarding the Fc molecule, including T m values of a CH2 and/or CH3 domain, such as T m 1 , T m 2 and/or T m 3, is considered a T m value, which is higher than the wild type ”; “ The introduction of the single point mutations e.g. improved the thermal stability of the Fc fragment by 4.5°C. The combination of stabilising mutations even showed a synergistic or at least an additive effect on thermal stability. A shift in the Tm values of the CH2 domain by approx. 9°C and for the CH3 domain by approx. 6°C could be gained by the combination of specific point mutations. ” Under MPEP 2144.05 In the case where the claimed ranges “overlap or lie insid e ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) . Similarly, a prima facie case of obviousness exists where the claimed ranges and prior ar t ranges do not overlap but are close enough that one skilled in the art would have expecte d them to have the same properties. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) . Generally, differences in concentration or temperature will n ot support the patentability of subject matter encompassed by the prior art unless th ere is evidence indicating such concentration or temperature is critical. “[W]here the ge neral 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) . To establish unexpected results over a claimed ran ge, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticali ty of the claimed range. In re Hill, 284 F.2 d 955, 128 USPQ 197 (CCPA 1960) (MPEP 716.02(d)). AS regards the claims that encompass a Fc mutation selected from position 250 and 428 : Hinton teaches stabilizing mutations at 25 0 and 428 subs t ituted with an o ther amine acid which are different from the unm odi fi ed F c -f u sion prot ein ( col. 10, l ines 8-10). The F c - fusion proteins of the present invention may comprise any of the recognized Ig subtypes ( col. 9, lines 15-16 ) at positions 2 5 0 and 428 (col. 10, lines 13-14) and shown i n Table 1 ( T250A/I/V and M428F) ). The M428F substitution may increase binding affinity for FcRn and/or an increase in serum half-life ( col. 11, lines 29-35 and 37-39). AS regards the claims that encompass a Fc mutation selected from position 2 87 and 309 : Liu teaches stabilized Fc variants at [0059] such as A287F , L309C, L309S, L309K, and L309E , that increase Fc R binding (Table 1) . Lui teaches I336 but does NOT teach it i s substitut ed with a Cys and being paired with 242Cys. AS regards the claims that encompass a Fc mutation selected from position 308 and 309: Reyes teaches stabilized Fc variants such as V308I, L309 M/K/P but especially the combination of V308I/L309K in Table 2.1 . Reyes teaches testing melting temperatures for the mutated Fc regions Tables 4 and 4.2. Reyes teaches 336 but does NOT teach it is substituted with a Cys and being paired with 242Cys. Reyes teaches L242P and L242I (Table 2.1). The references teach polypeptide comprising the mutated Fc regions. The references teach polynucleotides and vectors for expressing the mutated Fc regions. The references teach methods for making the Fc variants. An antibody half-life is correlated with its temperature stability, as both are influenced by the antibody's physical and chemical properties. Antibodies with higher thermostability, meaning they are less likely to denature or aggregate at higher temperatures, generally have longer half-lives. This is because increased thermal stability often indicates a more robust and conformationally sound structure that is less prone to degradation in the body and more resistant to the conditions that lead to a shorter half-life. Antibodies that are more thermally stable can maintain their structure and function for a longer period, both in storage and in the body, leading to a greater in vivo half-life. Biophysical properties like thermal stability can be used to predict an antibody's pharmacokinetics (PK), including its half-life and clearance. High temperature can cause irreversible denaturation and aggregation, which can shorten half-life. A more thermostable antibody is more resistant to this degradation. High thermostability is beneficial for therapeutic antibodies to ensure long serum half-life and for diagnostic antibodies to extend shelf life without needing cold-chain storage. Accordingly, where the references teach improving stability of Fc regions where serum-half life and temperature sensitivity are correlated, the POSA would have had sufficient reason to generate Fc variants at the residues at one or more of the positions to achieve improved functional properties. Conclusion 9. No claims are allowed. 10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT LYNN A. BRISTOL whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-6883 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Mon-Fri 9 AM-5 PM . 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, FILLIN "SPE Name?" \* MERGEFORMAT Wu Julie can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-5205 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. 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