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
Continued Examination Under 37 CFR 1.114
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 7/23/2026 has been entered.
Status of the Claims
2. 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. In the Response of 4/23/2026, Claims 5, 11, 17, 19, 21, 23, 24, 28-31 and 53 are amended, claims 6-10, 13-16, 20, 22, 25-27, 32-33 and 54-55 are cancelled, and new claims 60-62 are added. In the Response of 7/23/2026, Claims 5, 11, 17, 19, 21, 30-31, 40-41, 53, 56-59 and 61 are amended.
Claims 5, 11-12, 17-19, 21, 23-24, 28-31, 34-45, 47-48, 53, and 56-62 are the claims.
Applicants’ amendment of the claims raises new grounds for rejection.
Priority
3. USAN 17/999,477, filed 11/21/2022, and having 1 RCE-type filing therein, 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
4. As of 9/1/2026, 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.
Withdrawal of Objections
Claim Objections
5. The objection to Claims 5, 11-12, 17-19, 21, 23-24, 28-31, 34-45, 47-48, 53, and 56-62 because of informalities is withdrawn.
a) Claims 5, 11-12, 17-19, 21, 23-24, 28-31, 34-45, 47-48 are amended to clarify the Fc variant is a variant of a parental IgG Fc wherein the parental IgG Fc is a variant of a wild-type IgG Fc.
Claims 53, and 56-62 are amended to clarify the Fc comprises a parental IgG Fc.
b) Claim 5 is amended to replace to “which” with “that.
c) Claim 5 is amended to recite “wherein the Fc variant has an increased CH2 domain melting temperature (Tm) as compared to the parental IgG Fc
d) Claim 21 is amended to replace “which” with “that
e) Claims 40-41 are to delete “an antigen-binding antibody fragment” and “antibody fragment” respectively.
f) Claim 53 is amended to replace “which” with “that.”
g) Claim 59 is amended to recite “wherein the stability-enhancing amino acid mutations comprised by the Fc variant comprise 250V and 287F.”
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
6. The rejection of Claims 5, 11-12, 17-19, 21, 23-24, 28-31, 34-45, 47-48, and 60-62 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
a) Claims 5, 11-12, 17-19, 21, 23-24, 28-31, 34-45, 47-48, and 60-62 are amended to replace “based on” with positive language “is a variant.”
b) Claims 30 and 31 are amended are amended to clarify the Fc variant is a variant of a parental IgG Fc and where the parental IgG Fc is a variant of a wild-type IgG Fc.
c) Claim 31 is amended to clarify the Fc variant is a variant of a parental IgG Fc and where the parental IgG Fc is a variant of a wild-type IgG Fc.
d) Claim 61 is amended to recite “the stability-enhancing mutations.”
New Grounds for Rejection
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 applicant regards as his invention.
7. Claim 47 is 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.
Amend claim 47 to delete “suitable” in the phrase “under conditions suitable for expression”. The term “suitable’ is conditional and by implication, the method is, too.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
8. Claims 34-35 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 34 and 35 recite “as compared to the parental Fc.” Claims 34-35 depend from amened claim 5 that recites “a parental IgG Fc”, thus claims 34-35 are broadening in scope.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
9. Claims 5, 11-12, 17-19, 21, 23-24, 28-31, 34-45, 47-48, 53, and 56-62 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.
Claim interpretation
Claims 5, 11-12, 17-19, 21, 23-24, 28-31, 34-45, 47-48 are amended to clarify the Fc variant is a variant of a parental IgG Fc wherein the parental IgG Fc is a variant of a wild-type IgG Fc.
Claims 53, and 56-62 are amended to clarify the Fc comprises a parental IgG Fc.
“parental Fc”: the specification is unequivocal that a parental Fc may be a variant of a wild type Fc at
[0035] Certain embodiments of the present disclosure relate to methods of stabilizing an Fc (the parental Fc) by introducing one or more stability-enhancing mutations described herein into the Fc. Some embodiments of the present disclosure relate to methods of increasing the CH2 domain melting temperature (Tm) of an Fc (the parental Fc) by introducing one or more stability-enhancing mutations described herein into the Fc. The parental Fc may be a wild-type Fc or it may itself be a variant Fc that already includes one or more amino acid mutations, for example, to improve a function of the Fc region.
[0054] The parental Fc may be a wild-type Fc or it may itself be a variant Fc that already includes one or more amino acid mutations, for example, to improve a function of the Fc region. In some embodiments, the parental Fc may be an Fc that includes one or more amino acid mutations that functionally enhance the Fc region. In some embodiments, the parental Fc may be an Fc that includes one or more amino acid mutations that functionally enhance the Fc region but result in a decrease in stability as compared to a wild-type Fc. In some embodiments, the parental Fc may comprise one or more amino acid mutations that functionally enhance the Fc region but decrease the thermostability of the CH2 domain as compared to a wild-type Fc.
None of the claims define a parental IgG Fc structure on which the mutated Fc variants are based. “A parental IgG Fc structure”, a variant of a wild-type IgG Fc, and on which the inventive Fc variants are based, is a critical essential feature of the claimed invention. See for example MPEP 2163 stating in part:
"The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art."
"The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence."
MPEP 2163.05 stating in part:
"A claim that omits an element which applicant describes as an essential or critical feature of the invention originally disclosed does not comply with the written description requirement."
The omission of the core sequence for a parental IgG Fc fails to satisfy the structure/function correlation for the inventive Fc variants that are predicated on mutations to the parental IgG Fc. Still further, the claims substantiate a distinction between “a paternal IgG Fc” from its corresponding wild-type IgG Fc and from the Fc variants of the invention (see amended clams 30-31).
Disclosure in the Specification
The specification does not provide a per se definition for the sequence of a parental IgG Fc.
Information that can be surmised is that SEQ ID NO: 1 of Fig. 1 and based on trastuzumab provides the core scaffold from which Fc variants are derived.
“[0248] Scaffold 1: Full-size antibody (FSA) based on trastuzumab with homodimeric IgG1 Fc, SEQ ID NO:1.”
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Perhaps the disclosure provides another example for a parental IgG Fc at
[0260] “Template 1” indicates a replacement of the amino acid residues at positions 325-331 with the following sequence: STWFDGGYAT [SEQ ID NO:2].
The Sequence Listing does not add insight as to what sequence comprises a parental IgG Fc much less an example of a sequence that corresponds to the wild-type IgG Fc for the parental IgG Fc.
Based on the limited disclosure for a parental IgG Fc sequence in the entirety of the application, the POSA could reasonably conclude that Applicants were not in possession of the full scope of the invention from a structure/function correlation required under the written description requirements. MPEP 2163(II)(3)(a):
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that inventor was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613 (quoting the Written Description Guidelines, 66 Fed. Reg. at 1106, n. 49, stating that “if the art has established a strong correlation between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function”.). “Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function.” Id.
Conclusion
9. No claims are allowed.
10. 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 LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Julie can be reached at 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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/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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