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 1-29, 36, 37, 40-53, 55, 57, 59, 60, 65, 66, 68-71, 73-94 and 101-105 are pending upon entry of amendment filed on 1/15/26.
Applicant’s election of group I, claims 1-29, 36, 37, 40-53, 55, 57, 59, 60, 65, 66, 68 and 105 without traverse in the reply filed on 1/15/26 has been acknowledged.
Accordingly, claims 69-71, 73-94 and 101-104 are withdrawn from further consideration by the examiner, 37 CFR 1.142 (b) as being drawn to a nonelected invention.
The instant application comprises 7 independent claims and the invention relates a composition comprising about 1-10mM of succinate buffer, about 0.01% of polysorbate with or without a therapeutic protein and a container comprising the composition.
3. Applicant’s IDS filed on 5/12/23 and 5/1/24 have been acknowledged.
4. The oath filed on 5/3/23 has been acknowledged.
5. The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
6. 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.
7. Claims 22 and 27 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 at least 95% identical to SEQ ID NO:18 or 27 as in claims 22 or 27 of the instant application, respectively.
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 first and/or second binding domain comprising at least 95% sequence identity to SEQ ID No:18 or 27. This would encompass any 10-15 amino acid modifications of the binding domains. Thus, claims would encompass structurally unrelated antibodies. There is no art recognized correlation between structure and function of such classes of the molecules and modulators exhibiting the claimed specific functions of CD123, CD3, CD86 or IL-10 binding activities. For example, the specification discloses binding activities of dual antibodies (note p. 105-110 of the specification). The instant specification does not disclose a correlation between structure defined by “95% sequence identity” to the antibody set forth in SEQ ID NO:18 or 27. 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.
8. Claims 22, 27, 36, 37, 51, 59 and 60 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a composition comprising succinate at about 5mM and polysorbate at about 0.01% at pH of 5-7 comprising first and second binding domain comprising the amino acid set forth in SEQ ID NO:18, 27 or 31 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 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 at least 95% of SEQ ID NO:18 or 27 as recited in claims 22 and 27 of the instant application. Further, the instant specification fails to disclose how to reduce adsorption of therapeutic protein at 0.01ug/ml to about 2.0ug/ml.
Examples 1-3 show how the diluent comprising about 5mM of succinate buffer and about 0.01% polysorbate 80 in reduction of adsorption after 40oC for 270 days however the instant application fails to show reduction of adsorption comprising the therapeutic protein or the protein at least 95% of SEQ ID NO:18 or 27. The instant specification fails to show the studies encompassing the protein comprising at least 95% of SEQ ID NO:18 or 27 as well as the therapeutic protein comprising 0.01ug/ml to about 3ug/ml of protein. WO2018/057802 (IDS reference) discloses the therapeutically effective concentration of protein comprising CD3 and CD123 include 0.05mg/kg to 0.25mg/kg (p. 128). Wang et al (International Journal of Pharmaceuticals, vol. 183, p. 129-188, 1999) discloses the concentration of commercially available therapeutically effective protein ranges 1-20mg/ml (Note table 1, p. 134-136). The art does not recognize claimed protein ranges of 0.01ug/ml to 2.0ug/ml that is much lower than the art recognizes therapeutically effective concentrations.
As such, given that the reduction of adsorption effect for the excipients comprising succinate and polysorbate does not seem to be protein or protein concentration dependent, one concentration tested at 5mM succinate with 0.01% polysorbate in the absence of protein cannot be extrapolated the protein of less than 100% sequence identity and low concentration of protein at 0.01ug/ml to 2ug/ml 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.
9. 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.
10. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
11. Claim(s) 1-5, 7-9, 65, 66, 68 and 105 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by U.S. Pub.2013/0034580.
The ‘580 publication teaches compositions comprising about 5mM of succinate buffer at about 5.8, about 0.01% of polysorbate and a CRM197 polypeptide (readable upon therapeutic protein) (note claims 24-55). Claim 5 is included in that “about 0.008% polysorbate” reads on “about 0.01%”. In addition, the ‘580 publication further teaches that the composition is being delivered in syringes (claim 55, [23], p. 7) and containers comprising the compositions. Given that the container is safe and sterile and made of glass, claim 66 that is being free of latex is included in this rejection.
Moreover, the ‘580 publication teaches that the composition is being delivered various routes including injections (p. 8). Therefore, the reference teachings anticipate the claimed invention.
12. Claim(s) 1-11, 40-51, 65, 66, 68 and 105 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by U.S. Pub.2008/0112953.
The ‘953 publication teaches compositions comprising about 1-200 mM of succinate buffer at about 5.8, about 0.001-0.01% of polysorbate inclusive of 0.004-008% (p.8-10, [0091-0093], claims 48-70). In addition, the ‘953 publication further teaches that the composition is being delivered in syringes and intravenously (p.14, [0084], [121] ) and containers comprising the compositions. Further, the ‘953 publication teaches that the composition comprises antibody, includes fragments, scFv, IgG2 (p. 10-14). Given that the container is safe and sterile and made of glass, claim 66 that is being free of latex is included in this rejection.
Moreover, the ‘953 publication teaches that the composition comprising succinate and polysorbate stabilizes antibody and reduces aggregates (p. 8) and the administration routes include intravenous (p.9). Therefore, the reference teachings anticipate the claimed invention.
13. 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.
14. Claims 1-29, 36, 37, 40-53, 55-57, 59, 60, 65, 66, 68 and 105 are rejected under 35 U.S.C. 103(a) as being unpatentable over U.S. Pub.2008/0112953 in view of WO2018/057802 (IDS reference) or U.S. Pub. 2013/0129723.
The teachings of the ‘953 publication have been discussed, supra.
The disclosure of the ‘953 publication differs from the instant claimed invention in that it does not teach the use of CD3xCD123 bispecific antibody as in claims 12-28, 53, 57, 59-60 and IL10xCD86 as in claims 29 and 55 of the instant application.
The ‘802 publication teaches TRI130 that is identical to the CD3XCD123 of antibody having the claimed SEQ ID NO:18,27 and 31 (note SEQ ID NO:132, 312, 323) having the CDR’s set forth in SEQ ID NO:10-15, 19-24 as in claims 19-28. The bispecific antibody is configured to have CH2-CH3 and domains of IgG1-4 (p. 11-15, 19-28). The ‘802 publication teaches addition of pharmaceutically acceptable carrier for intravenous administration (p. 107) and the dose ranges from 0.1ug-100mg/kg (p. 106). Further, the ‘802 publication teaches dose adjustment response in Tables 11-12 for 10-100 fold differences. As the dose may vary from 0.1ug-100mg and the dose response is from 10-100, claims 36, 37, 42-43 and 52 reciting low ranges of antibody concentration and formulating excipients in concentrated form as the concentration of succinate buffer vary from 1-200mM are included in this rejection.
Likewise, the ‘723 publication teaches bispecific antibody comprising IL-10 and CD86 ([0052]) that associates with B cell malignancy and therapeutically effective in treatment of cancer (p. 29-35).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize CD3xCD123 bispecific antibody or IL-10xCD86 bispecific antibodies as taught by ‘802 or ‘723 publications into the succinate and polysorbate formulation taught by the ‘953 publication.
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 succinate and stabilizes various antibodies by reducing aggregates.
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.
15. No claims are allowable.
16. 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
January 28, 2026
/YUNSOO KIM/Primary Examiner, Art Unit 1641