RESPONSE TO APPLICANT’S AMENDMENT
1. Applicant's amendment, filed 01/06/2026 , is acknowledged.
2. Claims 22-29 are pending and under examination.
3. Applicant’s IDS, filed 01/13/2026, is acknowledged.
4. In view of the amendment filed on 01/06/2026, only the following rejections are remained.
5. 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.
6. Claims 22-29 stand rejected under 35 U.S.C. 103 as being unpatentable over US 20190106491 A1 or US 20210115140 A1, each in view of CN 110538321 or EP3479819B1 (IDS) for the same reasons set forth in the previous Office Action mailed 10/14/2025.
Applicant’s arguments, filed 01/06/2026, have been fully considered, but have not been found convincing.
Applicant submits that neither US 20190106491 A1 nor US 20210115140 A1 teach or suggest a pharmaceutically acceptable, stable liquid formulation comprising magrolimab and acetate buffer, sucrose, and polysorbate 20, or magrolimab, acetate buffer, trehalose, and polysorbate 20, as recited in the present claims at the recited concentrations and pH. Indeed, the Office Action acknowledged that "[t]he reference teachings differ from the claimed invention only in the recitation that the osmolality-adjusting excipients is 9% w/v sucrose or 9% w/v trehalose". Office Action page 3.
Applicant submits that the CN '321 publication does not teach or suggest formulations comprising magrolimab (Hu5F9-G4), much less in combination with the recited components at the recited concentrations and pH. Similar to the CN '321 publication, the EP '819 publication makes no mention of magrolimab at all, much less formulations comprising magrolimab, acetate buffer, sucrose, and polysorbate 20, or magrolimab, acetate buffer, trehalose, and polysorbate 20, at the particular concentrations as recited in the present claims. Applicant respectfully disagrees that the cited references would lead one of ordinary skill in the art to the present claims. The Office Action has not shown that the combination of references discloses all the elements of the present claims, nor that one of ordinary skill in the art would arrive at the present claims with a reasonable expectation of success. At least for these reasons, no prima facie case of obviousness has been established.
This is not found persuasive because the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference and not is it that the claimed invention must be expressly suggested in any one or all of the references; but rather the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). See MPEP 2145.
The examiner recognizes that obviousness can only be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine 5 USPQ2d 1596 (Fed. Cir 1988) and In re Jones 21 USPQ2d 1941 (Fed. Cir. 1992). In this case the teachings of `491 publication teaches the anti-CD47 antibody, Hu5F9-G4 (aka magrolimab) is supplied in single-use, 10 mL vials containing 200 mg (i.e., 20 mg/ml) of the antibody, in a formulation of 10 mM sodium Acetate (i.e., buffer), 5% (w/v) sorbitol (stabilizer), 0.01% (w/v) polysorbate 20 (surfactant), pH 5.0 [0135 ] and the teachings of the CN `321 and EP `819 publications indicating success in generating stable isotonic anti-CD47 antibody formulation with 8% sucrose or trehalose preparations (see CN `321) and that the 1-10% (w/v) concentration of sorbitol, mannitol, sucrose or trehalose may be freely controlled within a range that does not substantially adversely affect the stability and viscosity of the stable liquid formulation EP `819 would have led one of ordinary skill in the art before the effective filing date of the claimed invention to combine the references to substitute the sucrose or trehalose taught by the CN `321 and `EP `819 publications with sorbitol stabilizer in the aqueous formulation taught by the `491 and `140 publications, because like the sorbitol taught by the primary references, sucrose or trehalose at a concentration of 9% or the percentage that would result in 300mosm/kg which stabilizes the anti-CD47 antibodies preparations. "[W]hen a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result." KSR Int'l v. Teleflex Inc., 550 U.S. 398,416 (2007).
Given that the `491 , the `140 and the CN 321 and the EP `819 publications are concerned with pharmaceutical formulation and the `491 , the `140 and the CN 321 are concern with anti-CD47 antibodies , it would have been prima facie obvious to substitute one stabilizer with another stabilizer with reasonable expectation of success. Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious.” Id. at 301, 213 USPQ at 536. In this case, there is explicit suggestion in the secondary references that the tonicity agents/stabilizers are equivalent (see CN 321 and the EP `819).
Applicant demonstrated that the claimed formulations, which have a benefit of being safer for administration to pediatric patients, did not show loss of stability, relative to formulations comprising sorbitol. At the time of filing of the present patent application, a person of skill in the art would be aware that intravenous administration of sorbitol presented potential safety issues for pediatric patients. Because sorbitol is metabolized to fructose, it is contraindicated in pediatric patients with hereditary fructose intolerance and hypoglycemia. In severe cases it may cause damage of the liver accompanied with coma resulting in death in those patients. Especially intravenous administration of sorbitol should be avoided. See, page 23/45 of the EMEA/CHMP/PEG/194810/2005, "REFLECTION PAPER: FORMULATIONS OF CHOICE FOR THE PAEDIATRIC POPULATION" published by the COMMITTEE FOR MEDICINAL PRODUCTS FOR HUMAN USE (CHMP).
This is not found persuasive because Applicant is arguing limitations that are not claimed. The claims are not limited to subpopulation of pediatric patients having hereditary fructose intolerance and hypoglycemia. In the contrary, the claims are silent with respect to the targeted subpopulation and claim 25 explicitly recites any “individual”.
In Figure 7 of the application as filed, reproduced below, magrolimab formulations containing sucrose were associated with a higher melting temperature than formulations containing sorbitol. Thus, formulations comprising sucrose, while being safer for pediatric patients, were also shown to be more effective at stabilizing magrolimab formulations than sorbitol.
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This is not found persuasive because Applicant argues limitations that are not claimed with respect to the targeted subpopulation of pediatric patients. Also, is know in the art that sucrose often provides better stability at high temperatures due to stronger, direct protein binding.
7. No claim is allowed.
8. 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 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 mailing date of this final action.
. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 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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February 4, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644