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
1. The Amendment filed November 05, 2025 in response to the Office Action of June 09, 2025 is acknowledged and has been entered. Claims 2-20 and 25-27 have been cancelled. Claims 1, 22, 28, and 29 have been amended. New claims 30-32 have been added.
2. Claims 1, 21, 22, 24, and 28-32 are currently being examined.
New Grounds of Rejection
Claim Rejections - 35 USC § 112
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.
3. Claim 24 is 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.
Claim 24 recites the limitation " the anti-sclerostin antibody" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112
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.
4. Claim 24 is 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.
Claim 24 is drawn to the pharmaceutical composition of claim 1, comprising the anti-sclerostin antibody at a concentration of about 70 mg/mL to about 210 mg/mL. Claim 1 is drawn to a pharmaceutical composition comprising: (a) at least 70 mq/mL romosozumab. The a concentration of about 70 mg/mL is broader than at least 70 mq/mL. Thus, claim 24 fails to include all the limitations of the claim upon which it depends
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.
Claim Rejections - 35 USC § 103
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, 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
5. Claim(s) 1, 21, 22, 24, 29, 30 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Saag et al. (New Engl. J. Med. Oct. 12, 2017, 377(15): 1417-1427, IDS),”Saag” in view of US 2021/0347861 A1 (Lee et al. Nov. 11, 2021, filed Aug. 9, 2017), “Lee”.
Saag teaches that romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption. See abstract.
Saag teaches that in a blinded study that in postmenopausal women with osteoporosis who were at high risk for fracture, with 210 mg romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone. See abstract, Figures 1-3, and Table 2.
Saag teaches that rapid gains in bone mineral density from bone-forming therapy with romosozumab were associated with a lower risk of fracture than with alendronate within 1 year and over the course of romosozumab followed by alendronate. Hip fractures were less frequent with romosozumab followed by alendronate than with alendronate alone, suggesting an important benefit and challenging the common treatment practice of first-line use of alendronate in women who have had a previous fracture. See p. 1426.
Saag teaches as set forth above, but does not teach that romosozumab is in a pharmaceutical composition with histidine and sorbitol.
Lee teaches stable liquid pharmaceutical preparation of an anti-influenza virus antibody and, more specifically, a stable liquid pharmaceutical preparation that comprises: (A) an anti-influenza virus antibody or a mixture of two or more different types of anti-influenza virus antibodies; (B) a surfactant; (C) a sugar or a sugar derivative; and (D) an amino acid. See abstract.
Lee teaches testing pharmaceutical formulations for antibody stability. See Experimental Example 1:
Lee teaches testing pharmaceutical formulations with 10 mM Histidine, Sorbitol at 5% (w/v), polysorbate 80, at a pH of 6.0 and 25 or 50 mg/ml of antibody. See Table 1-Examples 1-9.
Lee teaches that the sorbitol/histidine antibody formulations were stable at 5, 25 or 40 °C after 6 weeks. See Experimental Example 2 and Table 2
Lee teaches that antibodies at 150 mg/ml were stable in the sorbitol/histidine antibody of Example 1. See ¶ 0223.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Saag and Lee use the sorbitol/histidine antibody formulations of Lee for pharmaceutical formulations of romosozumab because Lee teaches that the sorbitol/histidine antibody formulations provide extended stability of antibody for at least 6 weeks at room temperature at concentrations of 150 mg/ml. Thus, one would have been motivated to use romosozumab of Saag in the sorbitol/histidine antibody formulations of Lee at a concentration of at least 150 mg/ml to provide extended stability to the romosozumab pharmaceutical formulations.
Regarding claim 29, it is also noted that the limitation of “consisting essentially of “ will be assumed to be for examination purposes “comprising” because MPEP 2111.03 states:
For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, “consisting essentially of” will be construed as equivalent to “comprising.” See, e.g., PPG, 156 F.3d at 1355, 48USPQ2d at 1355.
6. Claim(s) 1, 21, 22, 24, and 28-32 are rejected under 35 U.S.C. 103 as being unpatentable over Saag et al. (New Engl. J. Med. Oct. 12, 2017, 377(15): 1417-1427, IDS),”Saag” in view of US 2015/0071936 A1 (Mendiratta et al. March 12, 2015), “Mendiratta”.
Saag teaches as set forth above, but does not teach that romosozumab is in a pharmaceutical composition with histidine or succinic acid and sorbitol.
Mendiratta teaches improved pharmaceutical protein formulations that stabilize antibody preparations. See abstract and ¶¶ 0007-0014, 0025, 0029 and 0031..
Mendiratta teaches that the antibodies can be at a concentration of from about 1 mg/mL to about 160 mg/mL See ¶¶ 0010 and 0024.
Mendiratta teaches that the formulations can comprise a histidine or succinate buffer in a range of about 5 mM to about 50 mM, preferably 10 mM. See ¶¶ 0025-0027, 0035, and 0081 and claims 10 and 37.
Mendiratta teaches that the pH of the buffer is in a range from 4 to 8, 5.0 to 5.5, or preferably 5.2. See ¶¶ 0011, 0028, 0062 and 0064 and claim 37.
Mendiratta teaches that the formulations can comprise sorbitol as stabilizer in amount about 1% to about 10%. See ¶¶ 0033 and 0034.
Mendiratta teaches that the formulations can comprise Polysorbate 80 or Polysorbate 20 as a surfactant. See ¶¶ 0029, 0030 and claim 25.
Mendiratta teaches that the formulations of the present invention are stable when kept at 2-8 °C and prevent aggregate formation. See ¶¶ 0006 and 0082.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Saag and Mendiratta use the sorbitol/succinic acid or histidine antibody formulations of Mendiratta for pharmaceutical formulations of romosozumab because Mendiratta teaches that the sorbitol/ succinic acid or histidine antibody formulations are stable and prevent aggregate formation. Thus, one would have been motivated to use romosozumab of Saag in the sorbitol/succinic acid or histidine antibody formulations of Mendiratta at a to provide stability to the romosozumab pharmaceutical formulations and prevent aggregation. Additionally, one of skill in the art would have been motivated to modify the sorbitol/succinic acid or histidine antibody formulations of Mendiratta to improve antibody stability as needed.
Regarding claim 28, it is also noted that the limitation of “consisting essentially of “ will be assumed to be for examination purposes “comprising” because MPEP 2111.03 states:
For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, “consisting essentially of” will be construed as equivalent to “comprising.” See, e.g., PPG, 156 F.3d at 1355, 48USPQ2d at 1355.
Conclusion
7. All other objections and rejections recited in the Office Action of June 09, 2025 are withdrawn in view of Applicant’s amendments and arguments.
8. No claims allowed.
9. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached on M-F 8:30-5:30 Eastern Time
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Janet L Epps-Smith can be reached on 571-272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Peter J Reddig/
Primary Examiner, Art Unit 1642