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 .
Response to Amendment
Applicant’s remarks and amendments to the claims received 11/10/2025 have been acknowledged. Claims 1 and 13 have been amended. Claims 2-4, 6-10, and 12 have been canceled. The amendments to the claims overcome the rejection made under 35 USC 112(a) written description previously set forth in the Non-Final Rejection of 07/08/2025.
Claim Rejections - 35 USC § 112
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.
Scope of Enablement
Claim 13 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an anti-D-dimer antibody defined by six non-degenerate CDRs does not reasonably provide enablement for an antibody comprising an extended HCDR2 sequence that incorporates additional residues from other heavy chain CDRs. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
While amended claim 1 defines an anti-D-dimer antibody by six CDRs with specific SEQ ID NOs, claim 13 (which now depends on claim 1) recites that the HCDR2 sequence (SEQ ID NO: 35) further comprises a sequence selected from two additional HCDRs (SEQ ID NOs: 36 and 37), thereby extending its length. In other words, the phrase “further comprises” requires the presence of the amino acid sequence of SEQ ID NO: 37 or SEQ ID NO: 38 in addition to the amino acid sequence of SEQ ID NO: 35 in the HCDR2 of the claimed anti-D-dimer antibody. However, the specification does not provide any structural or functional data showing that an antibody with such an extended HCDR2 (i.e. an HCDR2 comprising the amino acid sequence of SEQ ID NO: 37 or 38 in addition to the amino acid sequence of SEQ ID NO: 35) retains antigen-binding activity let alone the ability to bind to fibrin(ogen) fragments D-dimer, fragment DD, and fragment D but not to fragment E or fibrinogen. There is no evidence provided in the specification that antibodies incorporating the claimed extended HCDR2 sequences have the recited functional properties. In fact, the CDRs in antibodies often adopt restricted conformations based on the presence of specific amino acid residues at key positions in the CDRs and flanking framework regions (Sela-Culang, see “The Role of CDRs and their Definitions” section, in particular, “CDRs Identification” subsection). Thus, disrupting CDR structure (such as by extending HCDR2 length) can alter the structure of the antigen binding site and negatively impact antigen binding. Without evidence to the contrary, artisans would not reasonably expect anti-D-dimer antibodies comprising an extended HCDR2 region as recited in claim 13 to be capable of binding to antigen let alone binding to fibrin(ogen) fragments D-dimer, fragment DD, and fragment D but not to fragment E or fibrinogen.
Therefore, the specification is not enabled over the full scope of the claims.
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.
Claims 1,5,11,13-16 and 21-26 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.
The independent claim recites a recombinant anti-D-dimer antibody that binds to fibrin and fibrinogen degradation products (FDP) D-dimer, fragment DD, and fragment D but not to fragment E and fibrinogen. As presently written, it is unclear if the recombinant anti-D-dimer antibody of claim 1 binds to
fibrin(ogen) degradation products (i.e. fibrin degradation products and fibrinogen degradation products) including D-dimer, fragment DD, and fragment D.
fibrin (non-crosslinked or crosslinked) and fibrinogen degradation products, wherein the fibrinogen degradation products include D-dimer, fragment DD, and fragment D.
Per the specification, D-dimer is a fragment of cross-linked fibrin consisting of two crosslinked D domains and an E domain, which can be separated by urea extraction resulting in fragment DD and E (Background on Page 1). However, fragment D can be derived from either fibrinogen or fibrin as made readily apparent by Table 2 of the specification. Thus, it is also unclear if the recombinant antibody of claim 1 binds to fragment D derived from fibrinogen, fibrin, or both.
Lastly, fragment E can also be derived from either fibrinogen or fibrin as made readily apparent by Figure 1 and Table 2. However, it is not clear if the recombinant anti-D-dimer antibody of claim 1 does not bind to fragment E from fibrin, fibrinogen, or both.
Based on the epitope binning studies for antibody #12 (Table 2), it appears that the intended scope of claim 1 is limited to anti-D-dimer antibodies that bind to fibrin(ogen) degradation products including D-dimer, fragment DD, and fragment D (derived from both fibrinogen and fibrin) but do not bind to fibrinogen or fragment E (derived from either fibrin or fibrinogen). However, as presently written, the independent claim does not clearly set forth the metes and bounds of the patent protection desired. The dependent claims do not remedy the deficiencies of independent claim 1 and are thus also rejected.
Response to Arguments
Applicant's arguments filed 11/10/2025 with respect to rejections made under 35 USC 112(a) enablement and 35 USC 112(b) have been fully considered but they are not persuasive.
With respect to the rejection made under 35 USC 112(a) scope of enablement, Applicant argues that claim 13 has been amended to recite that the sequence of HCDR2 is selected from the group consisting of SEQ ID NO: 38 and SEQ ID NO: 37. Applicant states that both SEQ ID NOs: 37 and 38 are longer than SEQ ID NO: 35, comprise SEQ ID NO: 35, and are based on other definitions of antibody CDRs.
In response to Applicant’s arguments, the Examiner points out the claim 13 has only been amended to depend from claim 1 and still recites that “the amino acid sequence of HCDR2 further comprises a sequence selected from the group consisting of SEQ ID NO: 38 or SEQ ID NO: 37. The phrase “further comprises” requires the presence of the amino acid sequence of SEQ ID NO: 37 or SEQ ID NO: 38 in addition to the amino acid sequence of SEQ ID NO: 35 in the HCDR2 of the claimed anti-D-dimer antibody. For example, if the claimed anti-D-dimer antibody having an HCDR2 amino acid sequence of SEQ ID NO: 35 (DPDDSEA) (per claim 1) further comprises the amino acid sequence of SEQ ID NO: 37 (RIDPDDSETHYYNQKFKD), then the resulting HCDR2 amino acid sequence is the addition of both: DPDDSEA + RIDPDDSETHYYNQKFKD, or DPDDSEARIDPDDSETHYYNQKFKD. As discussed above, the specification does not provide any structural or functional data showing that an antibody with such an extended HCDR2 (i.e. an HCDR2 comprising the amino acid sequence of SEQ ID NO: 37 or 38 in addition to the amino acid sequence of SEQ ID NO: 35) retains antigen-binding activity let alone the ability to bind to fibrin(ogen) fragments D-dimer, fragment DD, and fragment D but not to fragment E or fibrinogen. The fact that the amino acid sequence of SEQ ID NO: 37 or 38 each fully comprise the amino acid sequence of SEQ ID NO: 35 does not negate the additive claim language of the phrase “further comprises”. Thus, the rejection of claim 13 under 35 USC 112(a) enablement is maintained.
Applicant may overcome this rejection by amending the independent claim to recite the following: “…a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 34 (HCDR1); an amino acid sequence selected from the group consisting of SEQ ID NO: 35, SEQ ID NO: 37, and SEQ ID NO: 38 (HCDR2); and the amino acid sequence of SEQ ID NO: 36 (HCDR3).”
With respect to the rejection made under 35 USC 112(b), Applicant argues that as amended claim 1, as well as claims dependent thereon, satisfy 35 USC 112(b) in that these claims particularly point out and distinctly claim the subject matter the inventors regard as the invention. Applicant further states that, as described in the specification, the claimed invention relates to recombinant antibodies that bind to D-dimer, fragment DD, and fragment D.
In response to Applicant’s arguments, the Examiner reiterates that as presently written, it is unclear if the recombinant anti-D-dimer antibody of claim 1 binds to 1) fibrin(ogen) degradation products (i.e. fibrin degradation products and fibrinogen degradation products) including D-dimer, fragment DD, and fragment D; or 2) fibrin (non-crosslinked or crosslinked) and fibrinogen degradation products, wherein the fibrinogen degradation products include D-dimer, fragment DD, and fragment D. Based on the epitope binning studies for antibody #12 (Table 2), it appears that the intended scope of claim 1 is limited to anti-D-dimer antibodies that bind to fibrin(ogen) degradation products including D-dimer, fragment DD, and fragment D (derived from both fibrinogen and fibrin) but do not bind to fibrinogen or fragment E (derived from either fibrin or fibrinogen). Applicant should amend the claim to clarify its scope. For example, claim 1 can be amended to recite the following: A recombinant antibody that specifically binds to fibrin degradation products and fibrinogen degradation products but does not bind to either fragment E or fibrinogen, wherein the fibrin and fibrinogen degradation products include D-dimer, fragment DD, and fragment D. The rejection made under 35 USC 112(b) is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
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/LIA E TAYLOR/Examiner, Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641