DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 1-2, 30, 31, 60, 63, 69, 80, 81, 89, 90 and 94-104 are pending upon entry of amendment filed on 11/19/25.
Applicant’s election of group I, claims 1-2, 30, 31, 60 and 97-104 without traverse in the reply filed on 11/19/25 has been acknowledged.
Accordingly, claims 61-63, 69, 80, 81, 89, 90, 94-96 are withdrawn from further consideration by the examiner, 37 CFR 1.142 (b) as being drawn to a nonelected invention.
Claims 1-2, 30, 31, 60 and 97-104 are under consideration in the instant application. Current amendment includes 2 independent claims and claims are drawn to a pharmaceutical composition comprising about 150mg/ml anti-Factor IX antibody set forth in SEQ ID NO:29 and 39, 20mM of histidine buffer, 220mM sucrose and about 0.04% polysorbate 20 at pH 5.5.
3. Applicant’s IDS filed on 1/18/23 (2 entries), 7/18/24 (2 entries) and 5/30/25 have been acknowledged. The applications listed in the IDS filed on 7/18/24 have been considered and treated as PTO-1449.
4. The oath filed on 1/11/23 has been acknowledged.
5. 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.
6. Claims 97-99 and 101-103 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 98 and 102 which depend on claims 1 and 30 recite SEQ ID NO:29 and 39, respectively. Given that the SEQ ID NO:29 and 39 are variable heavy and light chains, respectively, the variable heavy and light chains inherently comprise CDRs as well as the framework. As such, in lack of specifying CDR’s in sequence identifies, the variable heavy and light chains set forth in SEQ ID NO:29 and 39 inherently encompasses unspecified CDRs recited in claims 1 and 30. Especially in claims 97, 99, 101 and 103 reciting “90% identity” to SEQ ID NO:29 and 39 broaden the scope of the independent claims. 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.
7. 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.
8. Claims 97, 99, 101 and 103 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. Specifically, there is insufficient written description to demonstrate that Applicant was in possession of the claimed genus of compositions comprising “90% sequence identity” to SEQ ID NO:29, 31, 39 or 41.
The guidelines of the Examination of Patent Applications Under the 35 U.S.C. 112, §1 “Written Description” Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of 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 genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, see specially page 1106 column 3, MPEP2163).
In The Reagents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F.3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted: A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. See Fiers, 984F. 2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statue requires a description of an invention, not an indication of a result that might achieve if one made that invention. See In re Wilder 736 F.2d 1516,1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”). Accordingly, naming the type of material generally known to exist, in the absence of knowledge as to what that material consist of, is not a description of that material”.
The court has further stated that “Adequate written description requires a precise definition such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention”. Id. At 1566, 43 USPQ2d at 1404 (quoting at 1171, 25 USPQ2d at 1606). Also see (CAFC2002). Enzo-Biochem v. Gen-Probe Fiers, 984 F.2d 01-1230.
The instant claims are drawn to compositions comprising a huge genus of structurally distinct anti-Factor IX antibody comprising 90% sequence identity to SEQ ID No:29, 31, 39 or 41. This would encompass any 10-20 amino acid modifications of the antibodies and no guidance was provided in the specification. The SEQ ID NO:39 or 41 is variation of the SEQ ID NO:29 and 31, respectively. Thus, claims would encompass structurally unrelated antibodies comprising unguided modifications upto 20 amino acids. There is no art recognized correlation between structure and function of such classes of the antibodies exhibiting the claimed specific functions of treatment of patient with atrial fibrillation with antibody. For example, the specification discloses anti-Factor XI antibody in treatment of atrial fibrillation (note p. 90-100 of the specification). The instant specification does not disclose a correlation between structure defined by “90% sequence identity” to the antibody set forth in SEQ ID NO:29, 31, 39 or 41. Further, the disclosed species are not sufficiently representative of the huge genus encompassed by the present claims. Thus, one of skilled in the art would conclude that the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus of the claimed pharmaceutical compositions. See Eli Lilly, 119 F, 3d 1559, 43, USPQ2d, 1398.
9. Claims 97, 99, 101 and 103 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for pharmaceutical formulation comprising anti-Factor XI antibody set forth in SEQ ID NO:29, 31, 39, 41 in the presence of 20mM histidine buffer, 220mM sucrose, polysorbate at 0.04% at pH 5.5 does not reasonably provide enablement for more.
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 and/or use of the invention commensurate in scope with these claims. The claims are drawn to an anti-Factor XI antibody set forth in SEQ ID NO:29, 31, 39 or 41 or heavy or light chains comprising “90% identity thereto” of SEQ ID NO:29, 31, 39 or 41, respectively.
The specification does not enable one of skill in the art to practice the invention as claimed without undue experimentation. Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed.Cir.1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of the skilled in the art to practice the claimed invention.
There is insufficient guidance in the specification as filed as to how the skilled artisan would make and use anti-Factor XI antibody that is 90% identity to SEQ ID NO:29, 31, 39 or 41.
Examples in p. 100-139 showed treatment of diseases such as arthroplasty, atrial fibrillation comprising antibody I. No studies of how to make 90% sequence identity to SEQ ID NO:29, 31, 39 or 41 or treatment of how to use anti-Factor XI antibody that is 90% identity to SEQ ID NO:29, 31, 39 or 41.
As such, one antibody set forth in SEQ ID NO:29 or 39 in treatment of arthroplasty, atrial fibrillation cannot be extrapolated to any antibody comprising 90% identity to SEQ ID NO:29, 31, 39 or 41 encompassed by the claimed invention.
The specification fails to provide sufficient guidance to direct a person of skilled in the art to make and achieve the intended use of the claimed inventio without undue experimentation. It is unpredictable to develop antibody formulation and one exemplary structure disclosed in the example cannot be extrapolated to various antibody formulations encompassed by the claimed invention.
To summarize, reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view or the quantity of experimentation necessary, the limited working example, the unpredictability of the art, the lack of sufficient guidance in the specification, and the breath of the claims, it would take undue trials and errors to practice the claimed invention.
10. 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 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.
11. 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 of this title, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
12. Claims 1, 2, 30, 31, 60 and 97-104 are rejected under 35 U.S.C. 103(a) as being unpatentable over U.S. Pat. 10,465,011 (IDS reference) in view of U.S.Pub 2006/0088523.
The ‘011 patent teaches pharmaceutical compositions comprising anti-Factor XI antibody set forth in SEQ ID NO:29 and 39 (claims 1-16). The sequence search reveals claimed SEQ ID NO:29, 31, 39 or 41 are identical to the SEQ ID NO:29, 31, 39 or 41 of the ‘011 patent (see col 113-135). Given that the SEQ ID NO:29, 31, 39 or 41 are variable heavy or light chains, they are expected to comprise heavy or light variable CDR’s set forth in SEQ ID NO:3-5, 14, 15, 23-28, 33-38, 43-45 or 47 recited in claims 2 and 31 of the instant application.
In addition, the ‘011 patent teaches use of histidine buffer (L-histidine, co. 77), sucrose and polysorbate 20(col. 76) at pH 5-6 (specifying 5.5) and the concentration of antibody is from 75mg/ml to 200mg/ml (col. 76-77). Further, the ‘011 patent teaches intravenous administration of antibody inclusive of single bolus and dose of 1.5mg (col. 78). Claim 30 reciting 1.2mg/ml antibody in the presence of 0.2mM histidine buffer, 2.20mM sucrose and 0.0004% polysorbate and dextrose is included in this rejection as the systemic continuous infusion at 1-1000ug/ml of antibody in Remington’s ringer (essentially comprising dextrose at 5%).
The disclosure of the ‘011 patent differs from the instant claimed invention in that it does not teach the use of specific concentration of 20mM of histidine, 220mM of sucrose and 0.04% of polysorbate 20 as in claim 1 of the instant application.
The ‘523 publication teaches use of 20mM of histidine buffer, about 60-250mM of sucrose and about 0.0001-0.1% polysorbate. The antibody includes structurally unrelated antibodies of VEGF, HER2, DR5, CD20 and IgE (claims). The formulation comprising 20mM histidine, 60-250mM of sucrose and 0.0001-0.1% of polysorbate 20 reduces aggregates and improves stability.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize known buffer concentrations of histidine, sucrose and polysorbate as taught by the ‘523 publication into the antibody formulation taught by the ‘011 patent.
One of ordinary skill in the art at the time the invention was made would have been motivated to do so because the utilization of known concentrations improve stability and reduces aggregates of antibody composition and it is expected to work for various other antibodies of choice.
From the teachings of references, it would have been obvious to one of ordinary skill in art to combine the teachings of the references and there would have been a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of the ordinary in the art at the time of invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
13. No claims are allowable.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YUNSOO KIM whose telephone number is (571)272-3176. The examiner can normally be reached Mon-Fri 8:30-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Yunsoo Kim
Patent Examiner
Technology Center 1600
December 16, 2025
/YUNSOO KIM/Primary Examiner, Art Unit 1641