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 1-15, 17, 20 and 21 are pending upon entry of amendment filed on 12/22/25.
Applicant’s election of group II, claims 1-15, 17 and 21 without traverse in the reply filed on 12/22/25 has been acknowledged. The previous product claims are amended to recite method claims and included in Group II
Accordingly, claim 20 are withdrawn from further consideration by the examiner, 37 CFR 1.142 (b) as being drawn to a nonelected invention.
Claim 1-15, 17 and 21 are under consideration in the instant application.
3. Applicant’s IDS filed on 1/11/23, 11/11/23 and 7/3/24 have been acknowledged.
Foreign patent literatures and non-patent literatures are found in U.S.S.N. 16/083,321. In addition, non-English patent literatures are considered to its English abstract. Applicant is invited to submit English translation if further consideration is required.
4. The oats filed on 4/6/23 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 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. Claims 4, 10 and 11 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 pre-AIA the applicant regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "such as" and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949). In the present instance, claim 4 recites the broad recitation of antibody concentration of 1-200mg/ml and the claim also recites 90-180mg/ml which is the narrower statement of the range/limitation.
The use of the term “preferably” in claim 4 renders the claim indefinite because it is unclear whether the limitations following such terms or phrases are part of the claimed invention. See MPEP 2173.05 (h)III.
In addition, claims 10-11 recite improper Markush groups. The Markush groups recites the members as being “selected from the group consisting of A, B, and C”. Note MPEP 2173.05(h)
8. 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 1-15, 17 and 21 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of stabilizing anti-sclerostin antibody comprising a composition comprising an anti-sclerostin antibody set forth in CDR’s in SEQ ID NO:1-6, heavy and light chains set forth in SEQ ID NO:7-12, wherein the composition comprising 1-200mg/ml antibody, 10-55mM sodium acetate buffer, about 6% sucrose, 55-80mM of hydroxypropryl-gamma-cyclodextrin, 55-160mM of methionine in the presence of about 0.006% polysorbate 20 and a method of treating of improving bone mass comprising the above mentioned composition; 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 a pharmaceutical composition comprising an antibody set forth in claims 1 and 17.
Although various therapeutic antibodies are available in market (Wang et al, J. of Pharmaceutical Sciences, vol. 96, p.1-26) and generally know how to make therapeutic antibodies or antigen binding fragments thereof, claim 1 of the instant application does not specify any antigen target of the antibody. IN lack of specifying antigen target of antibody, the mere recitation of antibody is mutually exclusive in that the antibody may reach opposing endpoints. As evidenced by U.S. 7,592,429 discloses anti-sclerostin antibody that may improve bone density (example 9, col. 235-240). The ‘429 patent discloses that the anti-sclerostin treatment does not have any effect on colitis, the anti-sclerostin showed some inhibition of inflammation induced bone loss (col. 236).
However, WO2024/092133 discloses ACVR1 antibody that induces bone loss (see entire document). As such, the claimed antibody in claim 1 of the instant application is inclusive of mutually exclusive antibodies.
Further, Examples 1-4 exhibited beneficial effects of methionine and hydroxypropyl-gamma-cyclodextrin (HPGCD) in stabilizing anti-sclerostin antibody, no examples of treatment of bone disorder associated with bone mass or bone quality encompassed by claim 17. NO studies are disclosed in developing regimen, patient group, dose and/or toxicity studies of how to use sclerostin antibody in treatment of bone mass associated bone diseases encompassed by claim 17.
As such, given that the stabilizing effect for the excipient combination of methionine and HPGCD of anti-sclerostin antibody cannot be extrapolated any treatment method that is encompassed by the claimed method. It is unpredictable to develop therapeutic regimen wherein the stabilizing effect of antibody formulation comprising the excipient combination of methionine and HPGCD of anti-sclerostin antibody disclosed in the examples cannot be extrapolated to various disease treatment models 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. 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.
11. Claims 1 and 17 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being improper depended from for failing to further limit the subject matter of the claim upon which it depends, or failing to include all the limitations of the claim upon which it depends.
Claim 17 which depends on claim 1, recites the formulation while claim 1 recites the formulation that is being used in the method of claim 17. Claims 1 or 17 should be treated as the independent claim. However, in either case, the claim refers back to the other. Claim 1 reads on the method of claim 17 and purports to further limit the method to the use of a particular formulation.
However, claim 17 in turn purports to read on a method comprising administering the composition of claim 1. In either case, the claims fail to further limit the claims from which they depend since the limitations of those claims are mutually incorporated into each other. 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 requirement.
12. 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.
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 1-15, 17 and 21 are rejected under 35 U.S.C. 103(a) as being unpatentable over U.S. Pat 7,592,429 (IDS reference) in view of WO2013/164837.
The ‘429 patent teaches treatment of colitis induced bone density inhibition and inflammation induced bone mineral density comprising administering anti-sclerostin antibody composition (Examples 8-10, 12, col. 220, 235-240). The composition comprises various excipients (col. 217-219) including buffer, amino acids, sucrose that are suitable for injection. Claim 21 reciting reducing inflammation is included in that the prior art colitis is a species of inflammation. In addition, the ‘429 patent allows combination/or co-formulation of therapeutic antibodies in treatment of disease (p. 217-219).
Further, the ‘429 patent discloses the anti-sclerostin antibody set forth in the SEQ ID NO:7-12 (note SEQ ID NO:141 and 147) designating Ab-5 antibody (note col. 75-82). As the Ab-5 antibody set forth in the prior art SEQ ID NO:141 and 147 are humanized antibody, claims 5-7 are included in this rejection.
In addition, the claimed SEQ ID NO:11-12 is romosuzumab as in p. 24 of the instant application, claims 8 and 13 are included in this rejection. Moreover, claims 4, 12 and 13 reciting 1-200mg/ml are included in this rejection as the ‘429 patent suggests 30mg/kg-100mg/kg dose (col. 219) in 1 ml of volume for injection. Further, claims 14 and 15 reciting “the formulation is not a hydrogel” and “comprising at least 2% water”, respectively are included in this rejection as the ‘429 patent teaches the composition is in a liquid state; the liquid is not a hydrogel and is expected to comprise more than at least 2% of water.
The disclosure of the ‘429 patent differs from the instant claimed invention in that it does not teach the use of cyclodextrin, methionine and/or sucrose as in claims 1-4, acetate buffer as in claims 11-12 of the instant application.
The ‘837 publication teaches TNFalpha antibody formulation comprising a buffer including acetate, an amino acid including methionine, cyclodextrin including HPGCD and a sugar including sucrose (note claims 9-18, p. 6-10). The preferred concentration buffer is 5-50mM, amino acid concentration upto 0.5% (p.9) and cyclodextrin derivatives to 0.2-10% (p.9). The ‘837 publication teaches combinations of excipients stabilizes by reducing aggregates (p. 10-25).
Further, TNFalpha antibody including HUMIRA or adalimumab is being used in treatment of inflammation or colitis (p. 3).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to utilize specific excipient combinations as taught by the ‘837 publication into the sclerostin antibody formulation taught by the ‘429 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 acetate buffer, methionine, HPGCD and/or sugar is known to stabilize TNF-alpha antibody that is known to treat inflammation to sclerostin antibody formulation to improve stability by reducing aggregates. Given that both antibodies lead to treatment of inflammation, it is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for the same purpose in order to form third composition that is to be used for very same purpose; idea of combining them flows logically from their having been individually taught in prior art. In re Kerhkoven, 205 USPQ 1069, CCPA 1980, see MPEP2144.06. As taught by the ‘429 patent, col. 217, addition of buffer, amino acid and surfactant as excipients is not detrimental in formulating a pharmaceutical composition and allow other agents, the specific concentration that is suitable for TNF alpha antibody would be expected to stabilize anti-sclerostin antibody.
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 8, 2026
/YUNSOO KIM/Primary Examiner, Art Unit 1641