DETAILED ACTION
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 .
Terminal Disclaimer
The terminal disclaimer filed on April 15, 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of any patent that issues from US Application No. 18/999039 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Election/Restrictions
To summarize the election, the applicant elected the species where the respirable, dry powder particle surfactant formulation is that of claimed formulation number 72 and a pediatric patient population with respiratory distress syndrome, without traverse. The specification indicates that formulation 72 contains SEQ ID No. 9 as the SP-B surfactant protein (see page 74). This will be construed as the elected surfactant protein in the elected formulation since the claims and specification have been clarified.
Claim Interpretation
In previous office actions, an issue concerning the clarity and scope was raised due to the specification employing “SP-B” when referencing the full protein and then varying between reciting this same acronym alone or employing SP-B derivative, SP-B analogue, SP-B fragment, and SP-B peptide when referencing a derivative, analogue, fragment, or peptide thereof. Since the specification has been amended and claim 1 now recites “a SP-B surfactant protein… selected from the group consisting of: SEQ ID NOS: 1-16 or an amino acid sequence homologous thereto with at least 90% identity at the amino acid level” , the “SP-B” of claim 24 is viewed as a referencing a surfactant protein within this scope.
Claim Objections
Claim 24 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
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.
Claims 1-2, 5-6, 15-16, and 18-21 are rejected under 35 U.S.C. 103 as being unpatentable over Häfner et al. (previously cited) in view of Eistetter (previously cited), Blizzard et al. (previously cited), Clarke (previously cited), Notter et al. (previously cited), Walther et al. (previously cited), and Egan et al. (previously cited) as evidenced by Cunningham et al. (previously cited).
Häfner et al. teach a dry particle for inhalation of pulmonary surfactant (abstract and paragraph 15). The particle is envisioned to include phospholipids in combination with excipients as well as pulmonary surfactant protein B (SP-B) or surfactant protein C (SP-C), or one of their derivatives (see claim 4). Preferable phospholipids are a combination of dipalmitoyl- phosphatidylcholine (DPPC) and palmitoyl- oleyl-phosphatidylglycerol sodium (POPG-Na) at a ratio that ranges from 7:3 to 3:7 (see paragraph 11; instant claim 20). The desired pulmonary surfactant protein is more specifically taught present at 0.5 to 3 wt% (see paragraph 12). An example is provided composed of 69.3 wt% DPPC, 24.8 wt% POPG-Na, 2 wt% calcium chloride, 2.5 wt% palmitic acid, and 1.4 wt% recombinant SP-C (see examples 1; instant claims 1-2 and 20). Sodium chloride is taught as an alternative to calcium chloride (see paragraph 23). Häfner et al. further the teach the preparation of their dry particles via a spray drying and lyophilization procedure as detailed in WO 97/26863 authored by Eistetter (see paragraph 13). The teachings of Eistetter detail that their process generates particles at 1 to 5 mm in size that permits inhalation administration (see page 2 lines 66-77). They do not exemplify the SEQ ID No. 9 as a derivative of SP-B, the presence of sodium chloride, or hydrogenated starch hydrolysate (HSH), SD-30. While treatment of various pulmonary conditions, including acute respiratory distress syndrome, is taught, a pediatric human patient population is not explicitly detailed (see paragraph 15).
Blizzard et al. teach the inclusion of HSH in dry particulate pharmaceutical formulations administrable by inhalation in order to improve their chemical and physical stability (see paragraphs 5 and 7-8). The proportion of this component is at least 5 wt% and polyalditol is named as an envisioned variety composed of a blend of sorbitol maltitol, and higher order polyols (see paragraphs 10-14). They further teach obtaining a fine particle fraction less than 3.3 mm of at least 30% from spray draying the HSH containing mixture (see paragraphs 40 and 61). Blizzard et al. further teach that an aerodynamic diameter of 1 to 5 mm permits the particles to escape inertia and gravitational deposition in the oropharyngeal region to instead land in airways, particularly the deep lung (see paragraph 51).
Clarke teaches the use of HSH in pharmaceutical preparations (see paragraph 83). SD-30 is one of two particular varieties that are named (see paragraph 85). Cunningham et al. detail that SD-30 is a polyglycitol (see paragraph 5). Clarke also teaches the usefulness of polyalditol and HSH in the same capacity (see paragraph 83).
Notter et al. teach derivatives of SP-B for treating pulmonary disfunction due to surfactant deficiency (see paragraphs 14 and 65). One variety they exemplify is called Super Mini-B and has a sequence that fully matches instant SEQ ID NO. 9 (see paragraph 75, SEQ ID NO. 13, and example 3).
Walther et al. teach that Super Mini-B proteins yield superior oxygenation over SP-B when administered to a mammalian animal (see abstract, page 6 first column, and figure 14).
Egan et al. teach the treatment of acute respiratory distress syndrome and respiratory distress syndrome by administering a phospholipid in combination with SP-B or a protein that functions like SP-B (see page 3 lines 1-21 and claim 1). This condition is characterized by a deficiency in the quantity of lung surfactant (see page 1 lines 20-23; instant claim 1). The patient population is individuals that are at least one week old and a group of interest is pediatric patients (see page 4 lines 13-16 and claims 6-7; instant claims 17-18). A set of tested patients of interest were divided into age groups of less than one year, 1-5 years, 6-13 years, and greater than 13 years (see page 7 lines 15-16; instant claim 19).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to make the dry particles as Häfner et al. teach via the process of Eistetter because they state to do so and the result would be particles sized as Eistetter teach. While Eistetter does not state which type of diameter they recite, the fact that they teach the 1 to 5 mm sizing to be particularly suited for inhalation delivery and Blizzard et al. teach this same numerical range for aerodynamic diameter that is well suited to inhalation delivery to the lung, the artisan of ordinary skill would have viewed the size of Eistetter to be an aerodynamic diameter and/or found it obvious to generate this size from spray dry production as well as the preferred fine particle fraction of at least 30% smaller than 3.3 mm Blizzard et al. teaches. Within this production scheme, it would have been obvious to employ the example of Häfner et al. as a starting point for specific formulations within their scope and adjust the relative proportions of the DPPC and POPG-Na in the exemplified composition within the range that is taught. This range overlaps with that instantly claimed, thereby rendering it obvious (see MPEP 2144.05; instant claim 20). It also would have been obvious to employ a derivative of SP-B, namely the Super Mini B derivative of SP-B, in place of SP-C in the composition because Häfner et al. teaches the inclusion of SP-B, SP-C, and/or their derivatives. This modification would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome (e.g. specific SP-B derivative vs. generic SP-B derivative) and as the application of the same technique to a similar product in order to yield the same improvement. Here Notter et al. detail the utility of the Super Mini B protein and Walther et al. highlight its superior performance over SP-B, thereby rendering obvious its selection amongst known derivatives of SP-B. Routine work by the artisan of ordinary skill within the teachings of Häfner et al. that embrace a proportion of lung surfactant protein greater than 3 wt% would have been obvious and produces a range of proportions that overlap the “about 5 wt%” instantly claimed (see MPEP 2144.05; instant claim 5). Further, the exchange of sodium chloride for the calcium chloride in the product also would have been obvious because Häfner et al. teach the two salts as alternatives. This modification would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome. The addition of HSH in the dry particle formulation would have been obvious as the application of the same technique to a similar product in order to yield the same improvement that is taught by Blizzard et al. Further, selecting polyglycitol (SD-30) as the HSH would have been obvious because it was a known variety taught along with polyalditol by Clarke that is employed in pharmaceutical formulations (see instant claims 6 and 21). This choice would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome. The particle size distribution as well as proportions for the DPPC, POPG-Na, SP-B derivative SEQ ID No: 9, sodium chloride, and SD-30 meet, are close to, or overlap/embrace the ranges that are instantly claimed. Due to this proximity and the lack of evidence of the criticality of the selection of any of the claimed values, they are obvious in light of the prior art teachings and as a matter of routine work/design choice by the artisan. Given the teaching by Häfner et al. to administer their composition to treat acute respiratory distress syndrome (ARDS), it would follow to employ this resulting composition in this manner. More specifically, treating ARDS in a pediatric patient population, as delineated by Egan et al., by administering the modified composition of Häfner et al. would have been obvious because they teach the treatment of this condition with a combination of SP-B derivative and phospholipid which are the components provided by the modified Häfner et al. composition. Therefore claims 1-2, 5-6, 15-16, and 18-21 are obvious over Häfner et al. in view of Eistetter, Blizzard et al., Clarke, Notter et al., Walther et al. and Egan et al. as evidenced by Cunningham et al.
Allowable Subject Matter
The method of treating patients with a collection of composition embraced by claim 24 whose ratios are now clarified to be required and on a weight basis appear non-obvious in light of the prior art. Treating patients with the instantly claimed SP-B and elected SP-B was known and would have been obvious to provide via administering dried pulmonary particles comprising the claimed or elected surfactant in light of Häfner et al., Notter et al. and Walther et al. Pediatric populations were also recognized as benefiting from treatment with this surfactant. Häfner et al. provide the recited lipid combination as well as suggest both the presence of sodium chloride and SP-B or an SP-B derivative (including the elected derivative) and Blizzard et al. supports the inclusion of an HSH compound to confer stability. However, the combination of the required relative mass proportions and particle size distribution as well as the instant demonstration of correlation between the HSH proportion and particle size attained via spray drying points toward non-obviousness. Blizzard et al. provide teachings of HSH at 5 wt% or greater to achieve added stability in spray dried pulmonary particles that carry a protein active. Häfner et al. spray dry their composition and the technique they detail employing yield particles are all less than 5 mm and therefore have the claimed proportion with a fine particle fraction (FPF)<5.6 mm . However, the instant disclosure correlates the proportion of HSH in a spray dried DPPC and sodium chloride containing product impacting the final particle size, where the fraction with an FPF<3.4 mm decreases with decreasing proportion of HSH between 18 and 78 wt% (see instant specification table 15). This connection between the spray dried particle size of lipid containing particles and HSH proportion is not discussed by Blizzard et al. In addition, the claimed proportion of HSH is not near the lower end of the broad range of Blizzard et al. and is less than the lower end of the preferred range taught by Blizzard et al. Thus it is not clear that it would have been sufficiently predictable to achieve the claimed particle size distribution with the claimed proportion of components so as to perform the claimed method of treatment.
Response to Arguments
Applicant's arguments filed April 15, 2026 have been fully considered. In light of the amendment to the claims, the rejection under 35 USC 112(b) is hereby withdrawn. The rejection of claim 24 under 35 USC 103 is also withdrawn. The remarks directed toward the remaining rejections under 35 USC 103 are not persuasive.
The applicant argues that Häfner et al. require the divalent charge of calcium chloride for crosslinking to provide physical stability amongst the phosphates in the surfactant molecules of its composition. The basis of this argument is unclear, given that paragraph 12 of Häfner et al. states
“The pulmonary surfactant preparations can also contain electrolytes such as calcium, magnesium and/or sodium salts (for example calcium chloride, sodium chloride and/or sodium hydrogencarbonate) in order to establish an advantageous viscosity. Preferred preparations according to the invention contain 80 to 95% by weight of phospholipids, 0.5 to 3.0% by weight of pulmonary surfactant proteins, 3 to 15% by weight of fatty acid, preferably palmitic acid, and 0 to 3% by weight of calcium chloride.”
According to this text and the examples that do not include calcium chloride, this component is optional and is not required to be divalent in order to perform the intended function (see examples 1 and 5-6). Sodium chloride is explicitly named along with calcium chloride as options amongst three specifically named alternatives for an electrolyte that is desirable, yet optional, to include in the composition. Contrary to the applicant’s assertion, there is no mention of crosslinking nor ionic or electrostatic interaction between the electrolyte component and the lipid in the composition that Häfner et al. teaches that is required for stability. Thus the person of ordinary skill would have good reason to prepare the product of Häfner et al. employing sodium chloride as a component instead of calcium chloride and expect it to function as Häfner et al. states because they explicitly name them as alternatives in the same role. The fact that one compound contains a monovalent metal and the other a divalent metal does not negate the teaching by Häfner et al. that they are contemplated alternatives.
The applicant additionally asserts that Häfner et al. is “almost entirely” silent in regard to non-lipid excipient concentrations. As shown in the preceding paragraph quoting paragraph 12 of Häfner et al., the proportions for multiple non-lipid excipients are detailed. Thus, the text of Häfner et al. does not support the applicant’s assertion. The applicant quotes Häfner et al. as teaching surfactants as a “further” excipient which itself implies that other excipients were already discussed/contemplated by Häfner et al. While it is true that Häfner et al. do not teach the presence of the claimed hydrogenated starch hydrolysate, Blizzard et al. teach the benefit of the inclusion of HSH compounds in therapeutic protein containing pulmonary particle compositions as a stabilizing component as well as a range of proportions for such components that embraces the claimed range. Thus the prior art provided good reason to include the claimed hydrogenated starch hydrolysate and overlapping teaching for the amount. There is no evidence of record demonstrating an unexpected outcome or the criticality of the claimed range of proportions for HSH. The rejection cites MPEP 2144.05 to support the conclusion of obviousness for the claimed range of HSH proportion and does not merely rely upon an argument of routine optimization as the applicant characterizes. The first paragraph of this section of the MPEP notes that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed.Cir. 1990)”. Per applicant’s exhibit A, the rejection aligns more with slide 42 and the discussion of the prior art’s reason for the inclusion of hydrogenated starch hydrolysate paired with its teaching of contemplated proportions, as opposed to slide 41, referenced by the applicant, and its selection of a counterion for a compound based upon a rationale of obviousness that does not align with its fact pattern (e.g. differences amongst concentrations and temperature generally not supporting patentability absent evidence of criticality). Thus the rejection provided a reasoned rationale for the inclusion of the HSH in the composition of Häfner et al.
The applicant suggests that Blizzard et al. do not teach that the proportions of HSH they envision would be compatible with the system of Häfner et al. There is no evidence of record pointing to incompatibility due to the application of a greater than 5 wt% proportion of hydrogenated starch hydrolysate taught by Blizzard et al. in the particles of Häfner et al. Further, Blizzard et al. contemplate other excipients such as phospholipids and NaCl in the particles with hydrogenated starch hydrolysate, which is suggestive of the suitability of the combination of components set forth in the rejection (see paragraph 73 and table 7).
The applicant further argues that it would not have been obvious to replace palmitic acid of Häfner et al. with a hydrogenated starch hydrolysate and adjust its proportion upward. The rejection does not discussion making such a modification; therefore this argument is not salient to the prima facie case of obviousness that was set forth. Instead, the rejection discusses the obviousness of adding hydrogenated starch hydrolysate to the composition of Häfner et al. based upon the teachings by Blizzard et al. that its presence stabilizes therapeutic compounds in respirable, dry particles. The rejection then relies upon the range Blizzard et al. teach to inform the proportion of hydrogenated starch hydrolysate to include. Blizzard et al. teach that their concept is widely applicable to an array of proteinaceous therapeutic compounds. The claimed SP-B is a proteinaceous therapeutic compounds which aligns with the applicable actives contemplated by Blizzard et al. and there is no evidence of record to suggest that the protective effect of hydrogenated starch hydrolysate would fail in of the presence of this protein.
The applicant argues that prosecution has not been sufficiently compact. Specifically, they appear to argue that past claims were not always rejected by all the rejections in which they could have been, such that amendments with combinations of limitations that had not been rejected over prior art were still found to be obvious over prior art of record. The clarity in the recitation of “SP-B” has evolved over the course of prosecution and this evolution is the reason for the presence or absence of claims 4 or 23, from some rejections. In other cases, claims such as 13, 14, and 17 in the office action dated May 15, 2025 noted by the applicant, were not included in all prior art rejections because they were method claims and required additional prior art to meet their limitations that product claims did not. Consequently, product claims in this prior office action appeared in rejections focused on the product and in those that addressed the claimed methods. It is noted that the elected combinations of components whether in method or products have been rejected consistently rejected over prior art over the course of prosecution.
Contrary to the applicant’s characterization of complication in the rejection , the rejection provides the following aspects in the prior art that fit together to render the claimed invention obvious
A primary prior art reference teaching pulmonary particles with the claimed lipids, sodium chloride, and an SP-B surfactant with proportions as well as the benefit of the particle form over liquid pulmonary compositions.
A secondary reference motivating the addition of hydrogenated starch hydrolysate to the particles of the primary reference with proportions.
Secondary references detailing the synonymous terminology of hydrogenated starch hydrolysate as equivalent to or a member of the grouping polyalditol, polyglycitol, and Stabilite® 30 (SD-30).
Secondary references teaching SEQ ID 9 as a superior form of SP-B and its name as Super Mini-B.
A secondary reference teaching the recognized need for pulmonary administration of SP-B to pediatric patients.
The applicant comments on the number of cited references; however, sets of the references serve an explanatory role to elucidate terminology, as in the case of the hydrogenated starch hydrolysate and the elected SP-B derivative. Further, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991).
Conclusion
No claim is allowed.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
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/CARALYNNE E HELM/Examiner, Art Unit 1615
/MELISSA S MERCIER/Primary Examiner, Art Unit 1615
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