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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 of RCE on February 9, 2026 and amendment after final filed on February 9, 2026 has been entered. Claims 2-3, 10 were canceled, claims 1, 6-8 were amended and claims 16-20 were newly added. Claims 1, 4-9, 11-20 are pending in the instant application.
The restriction requirement was deemed proper and made FINAL in a previous office action. Claims 5, 9, 11-15 and 20 are/remain withdrawn from consideration as being drawn to a non-elected invention/species.
Claims 1, 4, 6-8, 16-19 are examined on the merits of this office action.
Withdrawn Objections/Rejections
The objections to claims for 6-7 and 8 are withdrawn in view of amendment of the claims filed February 9th, 2026.
The rejection of claims 1, 4, 6-8 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of amendment of the claims filed February 9th, 2026.
The rejection of claim(s)1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gaucher (WO2018208973) is withdrawn in view of amendment of the claims filed February 9th, 2026.
The rejection of claim(s)1 and 4 under 35 U.S.C. 103 as being unpatentable over Gaucher (WO2018208973) in view of Xiao (US20160102133 A1, cited previously) is withdrawn in view of amendment of the claims filed February 9th, 2026.
The rejection of claims 1, 4 on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of US Patent No.11261234 (referred to as US ‘234, previously US AN16/164208) in view of Gaucher (WO2018208973) (previous rejection was for AN16/164208, but it is now patented) is withdrawn in view of amendment of the claims filed February 9th, 2026.
The rejection of claims 1 and 4 on the ground of nonstatutory double patenting as being unpatentable over claims 64-83 of Co-pending AN 17/582289 in view of in view of Gaucher (WO2018208973) is withdrawn in view of abandonment of the copending Application.
New Objection
The amendment of the specification filed February 9, 2026 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows
As used herein, the term "SQ domain" or "SQ sequence" refers to a synthetic and shortened linker region that can replace the entire native hFVIll B-domain while maintaining the functional activity of the resulting FVIII polypeptide. The SQ domain serves as a minimal, non-native sequence that facilitates proper folding, intracellular processing and secretion of the modified hFVlll polypeptide in the absence of the B-domain. In some embodiments, the "SQ domain" or "SQ sequence" comprises a synthetic, shortened sequence set forth in SEQ ID NO: 7”. Applicants do have support for “comprises a synthetic, shortened sequence set forth in SEQ ID NO: 7 (SFSQNPPVLKRHQR)”. However, the remaining definition of “domain serves as a minimal, non-native sequence that facilitates proper folding, intracellular processing and secretion of the modified hFVlll polypeptide in the absence of the B-domain” is not supported and thus is considered new matter.
Applicant is required to cancel the new matter in the reply to this Office Action.
New Rejection
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.
Claims 1, 4, 6-7, 16-19 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.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Scope of the claims
Claim 1 recites an engineered human factor VIII polypeptide comprising the A1, A2, A3, C1 and C2 domains of hFVIII, wherein the engineered molecule comprises deletion of the entire B domain and the position of the deleted B domain is replaced by and “SQ” domain. Claim 1 further requires the recited substitutions in the A1 domain.
The application is originally filed expressly discloses in SQ domain. Paragraph 0032 states that the 908 amino acid B domain of FVIII can be replaced with an SQ domain (14 amino acid) while retaining the coagulation effect of full length FVIII. Paragraph 0032 identifies the resulting construct as FVIII-SQ and identifies the domains thereof as A1, A2 SQ, A3, C1 and C2. Figure 1 depicts the SQ region between the A2 and A3 portions of the polypeptide. Therefore, the rejection is not based on the absence of the term SQ domain from the application is filed but rather the issue is whether the application reasonably conveys possession of the full scope encompassed by an SQ domain.
Claim 1 does not limit the SQ domain to the particular 14 amino acid SQ sequence contemplated by the applicant. Previous evidence of record, Zhang, indicates that SQ/SQ type linkers or domains have differing amino acid sequences and these were known in the art. Thus, the term SQ domain encompasses structurally varying SQ sequences and is broader than the particular SQ species described in the application.
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed
Actual Reduction to Practice
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The Application as originally filed does not demonstrate actual reduction to practice of a representative number of structurally varying SQ domain species commensurate with the scope of claim 1. To the extent applicant made and tested an engineered FVIII construct containing the particular disclosed 14 amino acid SQ domain, such disclosure may demonstrate possession of that particular species. However, the specification does not identify the preparation and testing of multiple structurally different SQ sequences reflecting the diversity evidenced in the prior art. In particular, the specification does not demonstrate that the different SQ sequences were incorporated into the claim engineered construct containing the recited A1 domain substitution and determined to have the required or desired function.
Sufficient relevant identifying characteristic
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination thereof.
The application as filed also fails to disclose sufficient relevant identifying characteristics demonstrating possession of the full scope of the claimed SQ domain genus. The original specification identifies certain characteristics of a particular disclosed SQ peptide sequence which replaces the much larger native B domain and is positioned between A2 and A3 of FVIII and retains the desired function.
However, the specification does not identify the structural characteristics common to the broader group of SQ sequences encompassed by claim 1. For example, the specification does not identify a consensus amino acid sequence, conserved or required residues, allowable substitutions, degree of sequence identity or other structural characteristics. This is significant because there are differing SQ sequences within the prior art. The knowledge in the art that such different sequences existed does not necessarily establish that the applicant possessed such sequences in their particular engineered constructs.
Physical and/or chemical properties:
The data do not suggest the physical basis for the claimed activity and therefore do not describe which structure is required for the claimed functional properties. Understanding the physical basis for the claimed activity is critical to determining which of the sequences that meet the structural requirements of the genus also meet the functional requirements of the genus.
The application is originally filed also does not characterize the broader SQ domain through physical or chemical properties sufficient to demonstrate possession. Apart from identifying the particular SQ domain as being 14 amino acids in length, the specification does not identify common physical or chemical characteristics of the structurally varying SQ sequences encompassed by the claim. Accordingly the original specification does not provide physical or chemical identifying characteristics commensurate with the structural breadth of the claimed SQ domain
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification does not describe a general correlation between structure and function for the claimed genus. Paragraph 32 states that replacement of the B domain with the disclosed SQ domain retains the coagulation effect of the full length FVIII. Thus, the original disclosure provides a functional characteristics for applicants particular SQ containing construct. However, the original disclosure does not establish a sufficient correlation between structure of the different SQ sequences encompassed by claim one in their ability to provide the required or desired function when incorporated into applicants claimed engineered construct. The specification does not identify which residues of the disclosed SQ sequence are necessary for function, which residues may be substituted, what degree of sequence variation can be tolerated, or what structural features permit a different SQ sequence to replace the B domain while maintaining the desired functional properties. Thus, the mere existence of different SQ sequences in the prior does not establish that each such sequence would predictably possess the required properties when incorporated into the particular engineered polypeptide presently claimed including in combination with the recited substitutions. Thus, the present specification does not establish a known or disclosed structure function correlation from which a person of ordinary skill in the art could predict, based on the structure, that such sequence would successfully function as the B domain replacement in Applicants claimed construct. The proposed amendment does not establish written description support for the claim genus. Written descriptions support must be determined from the application as originally filed (see new matter objection to the specification above). The proposed functional characterization does not remedy this deficiency. The original application does not appear to disclose that an SQ domain, as a class, facilitates proper folding intracellular processing and secretion, nor does it identify what structural features of an SQ sequence produce those functions.
Method of Making
The specification provides support for preparation of a particular SQ construct using the specifically shown 14 amino acid SQ domain. However, the ability to make the particular species does not establish possession of the broader genus. The original disclosure does not provide structural criteria by which alternative SQ sequences can be selected as species expected to provide the required properties in applicants engineered construct. Absence of an established structure function correlation, alternative sequence would need to be selected and evaluated to determine whether the desired properties are obtained.
Conclusion
The application is originally filed demonstrates possession of a particular SQ domain comprising the 14 amino acid SQ domains sequence disclosed in paragraph 32 and in Figure 1. Claim 1 is not limited to that particular sequence and instead recites “SQ domain". Evidence of the record, including Zhang (previously provided), demonstrates that SQ/SQ type sequences having differing amino acid sequences were known in the art. Thus, the claim encompasses structural variation beyond the particular SQ embodiment described in applicants original disclosure. Therefore, the application is originally filed does not reasonably convey to a person of ordinary skill in the art the applicant had possession at the time of filing of the full scope of the SQ domain genus encompassed by claim 1 and subsequent dependent claims that do not define the specific SQ domain sequence.
Allowable Subject Matter
Claim 8 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERINNE R DABKOWSKI/Primary Examiner, Art Unit 1654
