DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Amendments to the Claims and Arguments/Remarks filed 15 September 2026, in response to the Office Correspondence dated 16 June 2026, are acknowledged.
The listing of Claims filed 15 September 2026, are examined. Claims 1-11 and 13-21 are pending. Claims 1, 5 and 6 are amended, claim 12 is canceled, and new claims 16-21 have been added.
Response to Amendment
The applicant amended claim 5 to recite that “the complex coacervate has a zeta potential in the range of -15 to +15 mV,” thereby replacing the previously objected-to formulation “-15 and +15 mV.” The amendment cures the informality identified in the prior Office Action. Accordingly, the objection to claim 5 is withdrawn.
Claim 12 has been canceled. Any outstanding rejection of claim 12 is therefore moot.
The applicant argues that the enablement rejection under 35 U.S.C.§112(a) should be withdrawn because amended claim 1 no longer expressly uses the word “preventing.” The enablement rejection of claim 1 and dependent claims 2-11 and 13-19 under 35 U.S.C.§112(a) is withdrawn.
Regarding the rejection of the claims under 35 U.S.C. § 103, The applicant correctly identifies an imprecision in the prior characterization of Liu that should be corrected for purposes of a prosecution record. Liu expressly demonstrates an LF-OPN complex formed because LF and OPN possess opposite charges and have high affinity for one another, and reports that the LF-OPN complex has greater stability toward in-vitro digestion and more effective intestinal-cell binding and uptake than the proteins individually. Liu should not, however, be characterized as explicitly stating that its material is the phase-separated complex coacervate now claimed. Accordingly, clarification of the factual basis of the rejection have been made as detailed below. However, the applicant’s arguments do not overcome the prima facie case of obviousness for claims 1-11 and 13-19. The applicant's Figure 4 evidence has been fully considered as objective evidence relevant to obviousness, nevertheless does not, on the present record, overcome the prima facie case for the breadth of amended claim 1.
The applicant's assertion that new claims 16-21 are patentable “for substantially the same reasons” has been considered but does not establish patentability merely because those limitations are expressly supported in the specification. Written-description support, however, is distinct from patentability over the prior art. The newly added claims are addressed by claim-specific prior art findings in the rejection outlined below.
Regarding the provisional nonstatutory double patenting rejection, the applicant requests that the provisional nonstatutory double-patenting rejection be withdrawn or held in abeyance until the claims are otherwise allowable because both sets of claims may change. MPEP § 804 expressly provides that a provisional double-patenting rejection should be made and maintained until it has been obviated or is no longer applicable, further states that a complete response requires either a showing that the claims are patentably distinct or a compliant terminal disclaimer, and that the issue should not simply be held in abeyance.
The possibility that one or both applications may later be amended does not obviate the present rejection. The rejection will be reconsidered if the reference claims actually change in a manner material to patentable distinctness. Accordingly, applicant's request to hold the provisional rejection in abeyance is denied, but the maintained rejection has been reframed claim-to-claim against the relevant claims of Application No. 18/720,338, with the reference specification used within the limits recognized by General Foods Corp. v. Studiengesellschaft Kohle mbH, 972 F.2d 1272, 1281 (Fed. Cir. 1992) and MPEP §804. The applicant may overcome the rejection by filing a terminal disclaimer under 37 CFR 1.321 or by establishing that the claims are patentably distinct.
Maintained Rejections
The following rejections are maintained from the previous Office Correspondence dated 16 June 2026, since the art which was previously cited continues to read on the amended/newly cited limitations.
Claim Rejections - 35 USC § 103
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-AlA 35 U.S.C. § 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AlA) 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.
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 and 11 are rejected under 35 U.S.C. § 103 as being unpatentable over Liu et al. (Assessment of bioactivities of the human milk lactoferrin-osteopontin complex in vitro. J Nutr Biochem. 2019 Jul;69:10-18; hereinafter “Liu”), in view of Cornish et al. (US-20030191193-A1, published 09 Oct 2003; hereinafter “Cornish”), and Poundarik et al. (US-20180280570-A1, published 04 Oct 2018; hereinafter “Poundarik”).
Liu teaches the claimed combination of lactoferrin (“LF”) and osteopontin (“OPN”). Liu explains that LF and OPN are multifunctional whey proteins naturally present at substantial concentrations in human milk and possess a high affinity for one another because they bear opposite charges, wherein LF is a basic glycoprotein whereas OPN is an acidic phosphorylated glycoprotein (p. 10, Abstract; p. 10, col. 2, LF is a basic glycoprotein while OPN is an acidic phosphorylated glycoprotein).
Liu prepares and experimentally characterizes an LF-OPN complex (p. 11, § 2.1, “Preparation and identification of the LF-OPN complex”; p. 12, Fig. 1A). Liu further reports that the LF-OPN complex possesses greater stability toward simulated gastrointestinal digestion and exhibits more effective binding and uptake by human intestinal cells than LF or OPN individually (p. 10, Abstract; pp. 13-16, Results and Discussion). Liu concludes that formation of the LF-OPN complex allows the proteins to protect one another against proteolysis and enhance their respective bioactivities (p. 10, Abstract; p. 16, Discussion).
Of particular relevance to the presently claimed physical form, Liu expressly characterizes the LF/OPN association in terms of coacervation, stating in its discussion that LF and OPN “coacervated the most” in forming the LF-OPN complex (p. 16, col. 1, ll. 3-4). This teaching is consistent with Liu’s underlying physicochemical explanation that the strongly interacting proteins bear complementary charges, LF being basic/cationic and OPN being acidic/anionic. Fig. 1A, showing higher molecular weight bands (p. 12) indicating complex formation. Thus, Liu teaches or at minimum particularly suggests an electrostatically formed LF-OPN coacervated complex comprising the two proteins recited in claim 1.
As evidence of the level of ordinary skill and the technical understanding of the term “complex coacervate” at the relevant time, Bovetto et al. (WO2012045801A1, published 12 April 2012; hereinafter “Bovetto”) is cited evidentially. Bovetto teaches that complex coacervates were a known class of food-grade protein assemblies produced by electrostatic interaction between lactoferrin and an oppositely charged protein and expressly teaches that proteins having an isoelectric point below pH 7 can serve as lactoferrin coacervation partners (p. 3, ll. 23-31; p. 4, ll. 18-30; p. 5, ll. 1-7). Bovetto further teaches that such lactoferrin complex coacervates are liquid protein-rich phases resulting from interaction of the oppositely charged proteins and may be prepared under known ranges of pH, ionic strength, protein concentration, mixing ratio, and temperature (pp. 4-6; claim 5). Thus, Bovetto demonstrates complex coacervation between lactoferrin and an oppositely charged acidic protein was an established phenomenon, such coacervation is driven by electrostatic protein-protein interaction, and acidic proteins having an isoelectric point below pH 7 were recognized as suitable LF complex-coacervation partners (pp. 3-6; claim 1). These propositions corroborate the technical significance that a skilled artisan would have attributed to Liu’s teaching that basic LF and acidic OPN possess a high-affinity electrostatic interaction and that LF and OPN “coacervated” in forming the investigated LF-OPN complex.
Bovetto is cited to corroborate the scientific understanding available to one of ordinary skill, namely, that electrostatic association of basic lactoferrin with a suitably acidic, oppositely charged protein was an established mechanism for producing lactoferrin-containing complex coacervates (see MPEP § 2144, § 2144.02, and § 2144.03 and In re Grose, 592 F.2d 1161, 1167-68 (CCPA 1979). Liu itself identifies OPN and its complementary charge relationship with LF. Bovetto is therefore evidentiary support for the technical significance of Liu’s expressly disclosed LF-OPN electrostatic/coacervating interaction, rather than a reference relied upon to substitute a different protein pair for Liu’s LF-OPN pair.
Liu does not expressly teach administering its LF-OPN complex for reducing or treating a metabolic bone disorder. Cornish supplies the reason to employ lactoferrin-containing compositions for that therapeutic purpose. Cornish teaches that lactoferrin is capable of stimulating skeletal growth and inhibiting bone resorption (¶[0004]). Cornish provides a method of preventing and treating bone-related disorders by administering an effective amount of lactoferrin to a subject in need thereof and specifically explains that the treatment operates, inter alia, through stimulation of skeletal growth and inhibition of bone resorption (¶[0009]).
Cornish further identifies bone disorders contemplated for lactoferrin treatment including osteoporosis, osteomalacia, rickets, osteopenia, glucocorticoid-induced osteoporosis, Paget’s disease, and additional disorders of skeletal metabolism (Abstract, ¶[0004], ¶[0007], ¶[0009]). Cornish therefore directly establishes that administration of LF for treating metabolic/skeletal bone disease was known prior to the instant effective filing date. Cornish additionally provides experimental in vivo evidence supporting the bone-growth activity underlying that therapeutic teaching. Cornish reports that local administration of lactoferrin to adult mice resulted in increased calvarial bone growth, with significant increases in bone area after five injections (¶[0034]).
Poundarik provides additional reason why retention of OPN in Liu’s LF-OPN complex would have been compatible with, and biologically relevant to, the bone-treatment objective taught by Cornish. Poundarik teaches compositions and methods directed to promoting bone/tissue mineralization and expressly incorporates OPN into bone-mineralization-promoting compositions (Abstract, ¶[0003], ¶[0004]). Poundarik specifically teaches that the non-collagenous bone proteins osteopontin and osteocalcin perform functions in promoting bone formation and tissue mineralization and describes OPN as participating in mineral nucleation and recruitment of ionic species relevant to skeletal mineralization (¶[0081]; see also ¶[0028], ¶[0030]-[0031] and Figs. 1, 7, and 9A-B).
Poundarik further describes methods of mineralizing tissue using substances containing osteopontin (claim 1) and demonstrates the use of OPN-containing matrices in bone-related applications (Abstract, ¶[0028], ¶[0030]-[0031] and Figs. 7 and 9A-B). Poundarik provides evidence that OPN was a biologically appropriate bone-associated protein whose presence in Liu’s LF-OPN complex would not have been expected to defeat Cornish’s bone-directed use and instead would have been consistent with an objective of supporting bone formation and mineralization.
Thus, it would have been prima facie obvious to one of ordinary skill in the art, prior to the instant effective filing date, to administer the LF-OPN complex taught by Liu for the bone-treatment purpose taught by Cornish. Liu teaches a naturally relevant LF-OPN association formed because the two proteins possess strongly complementary electrostatic properties and further demonstrates that formation of the LF-OPN complex increases resistance to gastrointestinal proteolysis and improves binding and uptake by intestinal cells relative to the individual proteins. Liu therefore teaches advantages to administering LF in association with OPN rather than merely as unassociated LF. Cornish independently teaches that LF is a bone-active protein capable of stimulating skeletal growth and inhibiting bone resorption and expressly teaches administration of LF to subjects for prevention and treatment of bone-related disorders. A person of ordinary skill seeking to administer LF for Cornish’s known bone-health purpose therefore would have had reason to employ Liu’s LF-OPN associated form because Liu teaches that association with OPN improves the stability and intestinal interaction of LF. Poundarik provides an additional reason to retain OPN in the composition rather than separate LF from OPN before administration because OPN was independently known to participate in bone formation and tissue mineralization.
The prior art itself supplies the particular LF-OPN pair and its electrostatically driven/coacervating association and enhanced gastrointestinal stability and intestinal uptake, from Liu; the therapeutic reason to administer LF to stimulate skeletal growth, inhibit bone resorption, and treat bone disorders, from Cornish; and the recognized relationship of OPN to bone formation and mineralization, from Poundarik. The combination amounts to applying a known biologically advantageous form of LF (i.e., Liu’s LF-OPN complex) to a known therapeutic use of LF (i.e., Cornish’s bone-treatment method) with OPN itself having a known bone-mineralization relationship as evidenced by Poundarik.
This reasoning is consistent with KSR International Co. v. Teleflex Inc., 550 U.S. 398, 417-18 (2007), which explains that when a known technique or known element is used according to its established function to obtain a predictable result, the combination may be obvious, and that an obviousness analysis may account for the inferences and creative steps that a person of ordinary skill would employ (see also MPEP § 2141 and § 2143). The rejection does not rest on the proposition that the prior art must expressly instruct the artisan to combine the references in the exact language of the claim. A reason to combine may arise from the nature of the problem to be solved and knowledge generally available to a skilled artisan, provided the reason is articulated and supported by evidence.
A person having ordinary skill in the art would also have had a reasonable expectation of success in doing so because Liu experimentally establishes that LF and OPN associate strongly because of their complementary charges and demonstrates that the resulting LF-OPN complex survives simulated gastrointestinal digestion better than the individual proteins and exhibits increased intestinal-cell binding and uptake (Abstract; pp. 11-16). Cornish establishes that LF itself possesses the relevant biological activity. Cornish reports stimulation of osteoblast and chondrocyte proliferation, inhibition of osteoclast development, and increased bone growth in vivo and teaches the use of LF to treat bone-related disorders (¶[0004], ¶[0009], ¶[0033]-[0034]). Poundarik confirms that OPN was not an arbitrary or biologically incompatible partner in a bone-health application but instead was recognized as a component involved in bone formation and tissue mineralization. Finally, Bovetto provides evidentiary support that complex coacervation of lactoferrin with acidic, oppositely charged proteins was an established and technically predictable phenomenon before the instant effective filing date. Thus, the skilled artisan was not required to discover either the general LF coacervation mechanism or the LF-OPN affinity from first principles.
Here, the references provide substantially more than an invitation to experiment: Liu experimentally establishes the particular LF-OPN interaction and beneficial properties of the resulting complex, Cornish experimentally establishes LF’s bone anabolic/anti-resorptive effect, and Poundarik independently connects OPN to bone formation and mineralization. Accordingly, one of ordinary skill in the art would have had reason to administer Liu’s LF-OPN coacervated complex to a subject requiring treatment of a metabolic bone disorder according to the therapeutic teachings of Cornish, with a reasonable expectation that LF’s known bone-promoting activity would be retained while Liu’s complex provided advantageous stability and delivery characteristics. Instant claim 1 therefore would have been obvious.
Instant claim 11 depends from claim 1 and further requires that the complex coacervate “increases bone growth and/or bone strength.” The additional limitation does not patentably distinguish the claimed method. Cornish teaches that lactoferrin is capable of “stimulating skeletal growth and inhibiting bone resorption” (¶[0004]) and describes preventing and treating bone-related disorders through stimulation of skeletal growth and inhibition of bone resorption (¶[0009]). More particularly, Cornish experimentally reports an in vivo bone-growth response, wherein local administration of lactoferrin to adult mice resulted in increased calvarial bone growth, including significant increases in bone area after five administrations (¶[0034]).
Thus, the “increases bone growth” alternative recited by instant claim 11 is a demonstrated biological effect of LF in Cornish. One of ordinary skill in the art would reasonably have expected the bone-growth activity taught by Cornish to remain available when LF was administered in Liu’s LF-OPN complex because Liu demonstrates that complex formation does not destroy LF but instead provides increased digestive stability and intestinal-cell interaction, while Poundarik establishes that OPN itself is associated with bone formation and tissue mineralization. Accordingly, for the reasons stated for instant claim 1 and because Cornish teaches the additional increased-bone-growth limitation, instant claim 11 likewise would have been obvious over Liu in view of Cornish and further in view of Poundarik.
Claims 1-10 and 13-15 are rejected under 35 U.S.C. § 103 as being unpatentable over Liu et al. (Assessment of bioactivities of the human milk lactoferrin-osteopontin complex in vitro. J Nutr Biochem. 2019 Jul;69:10-18; hereinafter “Liu”), in view of Cornish et al. (US-20030191193-A1, published 09 Oct 2003; hereinafter “Cornish”), and Poundarik et al. (US-20180280570-A1, published 04 Oct 2018; hereinafter “Poundarik”), as applied to claim 1 above, and Bovetto et al. (WO-2012045801-A1, published 12 Apr 2012; hereinafter “Bovetto”).
As to instant claim 2, Bovetto describes a particular LF-containing complex coacervate consisting of lactoferrin, another protein having an isoelectric point below pH 7, and water, wherein the total protein concentration is approximately 5-25 wt% (p. 11, ll. 9-20). That disclosed range lies entirely within the claimed 5-50 wt% range. An expressly disclosed prior-art range falling within or overlapping a claimed range supports a prima facie case of obviousness (see In re Peterson, 315 F.3d 1325, 1329-30 (Fed. Cir. 2003); MPEP § 2144.05).
As to instant claim 3, the same Bovetto embodiment teaches approximately 5-25 wt% total protein with the remainder being water (p. 11, ll. 9-20), corresponding to approximately 75-95 wt% water. That range overlaps and falls within the claimed 50-95 wt% water range. Instant claim 3 therefore likewise recites an expressly suggested composition range. As to instant claim 4, Bovetto teaches LF complex coacervates having an average diameter of at least 500 nm in the shortest dimension, with preferred larger values also disclosed (p. 4, ll. 25-30; claim 3). The claimed ≥500 nm limitation is therefore taught rather than inferred from the mechanism of coacervation.
As to instant claim 5, Bovetto expressly teaches an LF complex coacervate having a surface ζ-potential in the range of approximately −15 mV to +15 mV and discloses still narrower preferred ranges (p. 4, ll. 1-17 and ll. 25-30; claim 4). The numerical limitation of instant claim 5 is thus directly disclosed by Bovetto. As to instant claim 6, Bovetto teaches compositions comprising its complex coacervates and expressly contemplates their incorporation into edible nutritional products for administration to human or animal subjects (pp. 9-10; claim 13). Administration of the LF-OPN coacervate of the base combination “in a composition” therefore would have been expressly suggested. As to instant claim 7, Bovetto identifies oral/enteral compositions selected from food compositions, pet food compositions, drinks, nutritional formulas, and nutraceuticals (p. 10, ll. 22-28; claim 13), substantially corresponding to the alternatives recited in instant claim 7.
As to instant claim 8, The base combination teaches the LF-OPN pair, conversion thereof to an LF complex coacervate, oral nutritional administration, and administration to infants for the reasons stated above. Evidentiary reference Jiang et al. (Evaluation of Bioactivities of the Bovine Milk Lactoferrin–Osteopontin Complex in Infant Formulas, J. Agric. Food Chem. 68:6104–6111 (2020); hereinafter “Jiang”), provides an especially direct teaching of the claimed product form. Jiang studies bovine LF and OPN together in infant-formula matrices, including LF:OPN ratios of 3:1, 5:1, and 8:1, and reports that formation of the LF-OPN complex increases stability toward gastrointestinal digestion and retains/enhances relevant bioactivities. Jiang concludes that adding bovine LF and OPN to infant formulas can increase stability and bioactivity of the proteins (Abstract).
Jiang does not itself establish that the LF-OPN material is a complex coacervate, and it is not relied upon for that limitation. Rather, Bovetto supplies the coacervate teaching, while Jiang supplies a direct reason to implement the Liu LF-OPN combination in the specific infant-formula product form recited as one alternative in instant claim 8. Thus, a person having ordinary skill in the art would have had reason to formulate the LF-OPN coacervate of the base combination into an infant formula because Liu and Jiang identify LF-OPN as a milk-protein combination having advantageous digestive stability and intestinal bioactivity, Jiang evaluates that combination in infant formula, and Bovetto teaches that LF complex coacervates are food-grade and suitable for administration to infants. The skilled artisan would have had a reasonable expectation that the proteins could be incorporated in such a nutritional matrix because Jiang demonstrates compatibility of the same LF/OPN pair with infant formula and Bovetto provides operative LF-coacervation conditions. Accordingly, instant claim 8 would have been obvious.
As to claim 9, Bovetto expressly states that the compositions may be administered orally or enterally to humans and animals (p. 10, ll. 22-28). Liu independently evaluates the LF-OPN complex under simulated gastrointestinal-digestion conditions and intestinal-cell uptake. Oral administration of the resulting food-grade LF-OPN coacervate therefore would have been directly suggested by the combined references.
As to instant claim 10, The base combination teaches the claimed LF-OPN complex-coacervate administration. Evidentiary reference Belldegrun et al. (US-20190167766-A1, published 06 June 2019; hereinafter “Belldegrun”) teaches enteral nutritional formulations containing both LF and OPN. Among the disclosed formulations are approximately 0.85 g/L LF plus 0.13 g/L OPN, for approximately 0.98 g/L combined LF+OPN, and formulations having higher combined concentrations, including approximately 1.67 g/L LF+OPN (Table 3 and associated formulation disclosure). In addition, evidentiary reference Brune and Donn (Enteral Feeding of the Preterm Infant, NeoReviews 19(11), 2018; hereinafter “Brune”) describes approximately 150-160 mL/kg/day as a conventional target enteral feeding volume for preterm infants. Using the conservative 150 mL/kg/day value with Belldegrun’s 0.98 g/L LF+OPN formulation yields approximately: 0.98 g/L × 0.150 L/kg/day = 0.147 g/kg/day = 147 mg LF+OPN protein/kg/day. Using Belldegrun’s approximately 1.67 g/L combined concentration yields approximately 250.5 mg LF+OPN protein/kg/day at the same feeding volume.
Because claim 10 recites the amount of the complex coacervate, rather than merely the mass of LF+OPN protein, the total coacervate dose is more appropriately derived using Bovetto’s expressly disclosed dense-phase composition. Bovetto teaches approximately 5-25 wt% total protein with the balance water (p. 11, ll. 9–20). A coacervate supplying 147 mg protein/kg/day therefore corresponds to approximately 588-2,940 mg coacervate/kg/day when the coacervate contains 25-5 wt% protein.
Likewise, 250.5 mg protein/kg/day corresponds to approximately 1,002-5,010 mg coacervate/kg/day over the same Bovetto protein-content range. Each calculated range falls well within claim 10’s 100-10,000 mg/kg/day range. The calculations do not constitute a representation that Belldegrun itself expressly reports a coacervate dose, rather, they demonstrate the amount resulting when Belldegrun’s conventional LF+OPN nutritional exposure is implemented using Bovetto’s expressly disclosed coacervate composition.
It would have been obvious to employ LF/OPN exposure levels already taught as suitable for enteral nutritional administration when formulating the same proteins into the food-grade coacervate form suggested by Liu and Bovetto. The skilled artisan had an express reason to select a physiologically administrable amount because Cornish teaches administration of an “effective amount” of LF for bone treatment and explains that dosage and route can be selected in view of the subject and therapeutic circumstances (¶[0019], ¶[0021]). Moreover, where the art supplies an operable administration range and biological response is dose-dependent, routine determination of an appropriate amount ordinarily constitutes optimization of a known result-effective variable rather than invention of a new therapeutic principle (see In re Aller, 220 F.2d 454, 456 (CCPA 1955); In re Boesch, 617 F.2d 272, 276 (CCPA 1980); MPEP § 2144.05). The cited nutritional concentrations, conventional feeding volumes, and Bovetto coacervate composition produce calculated total-coacervate doses falling squarely within instant claim 10. Belldegrun and Brune are relied upon only for the conventional LF/OPN nutritional exposure and administration volume. Liu, Bovetto, and Cornish supply, respectively, the LF-OPN association, LF complex-coacervate form, and bone-treatment motivation. Accordingly, instant claim 10 would have been obvious.
As to instant claim 13, Bovetto expressly states that the complex-coacervate compositions are suitable for all age groups, including children and infants younger than twelve months (p. 11, ll. 3-8). Because instant claim 13 is satisfied by any member of its recited group, Bovetto’s express disclosure of children and infants meets the additional limitation. As to instant claim 14, Bovetto’s express statement that the composition is suitable for “all age groups,” together with its general teaching of administration to human subjects, encompasses administration to adults (p. 11, ll. 3-8).
As to instant claim 15, Bovetto expressly teaches administration of its edible complex-coacervate compositions to animals, including pet animals (p. 10, ll. 22-28). Instant claim 15 therefore recites an expressly contemplated recipient population.
The motivation to combine and reasonable expectation of success for the instant claims are the same as set forth for instant claim 1. In particular, the additional claimed size, ζ-potential, protein/water composition, dosage-form, route, and subject limitations are not unrelated optimizations imported from a remote technology, they are operating characteristics and uses expressly disclosed by Bovetto for lactoferrin-containing complex coacervates.
Claim Rejections – Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
Claims 1-11 and 13-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 13 of co-pending U.S. Application No. 18/720,338 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the reasons outlined below. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Reference claim 1 claims the same LF/OPN complex coacervate used in instant claim 1, while reference claim 13 claims administration of an LF/OPN complex to a subject for treatment or prevention of metabolic disorders. The substantive difference is the express limitation in instant claim 1 to reducing the frequency, occurrence, duration and/or severity of, and/or treating, a metabolic bone disorder using the complex specifically in its coacervate form.
That difference does not establish patentable distinctness. The utility supporting reference claim 1 expressly includes administration of the claimed LF/OPN complex coacervate to promote bone development, growth and strength and to prevent and/or treat bone disease and identifies metabolic bone disease as one such bone disease. Reference claim 13 separately establishes that administration of an LF/OPN complex for treatment or prevention of a metabolic disorder is itself claimed subject matter. Thus, instant claim 1 does not introduce a new active composition or an unrelated therapeutic use; it selects the expressly identified LF/OPN coacervate of reference claim 1 and employs it for an expressly disclosed bone-related metabolic therapeutic utility.
A person of ordinary skill in the art considering the invention defined by reference claims 1 and 13 in light of the utility supporting those claims would therefore have regarded administration of the claimed LF/OPN complex coacervate to a subject having or at risk for a metabolic bone disorder as an obvious species of the claimed LF/OPN therapeutic invention. The recited reduction in frequency, occurrence, duration and/or severity is a therapeutic or preventive consequence encompassed by treating or preventing the disorder and does not impart a patentably distinct administration or composition (see Geneva Pharms., Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003); AbbVie Inc. v. Mathilda & Terence Kennedy Inst. of Rheumatology Tr., 764 F.3d 1366, 1374-80, 112 USPQ2d 1001, 1006-11 (Fed. Cir. 2014)). Instant claim 1 is therefore not patentably distinct from reference claims 1 and 13.
Instant claim 2 further requires that the administered coacervate comprise protein in an amount of 5-50% w/w. Reference claim 2 expressly claims the same 5-50% w/w protein limitation for the LF/OPN complex coacervate. Thus, the additional limitation of instant claim 2 is itself an expressly claimed property of the same coacervate underlying the rejection of instant claim 1. Employing that specifically claimed coacervate in the bone-treatment method determined above to be an obvious variant would not have required inventive modification and produces no patentable distinction. Instant claim 2 is therefore not patentably distinct from reference claims 1, 2, and 13.
Instant claim 3 further requires 50-95% w/w water. Reference claim 3 expressly claims the identical water-content range for the LF/OPN complex coacervate. For the same reasons stated for instant claims 1 and 2, administering the specifically claimed coacervate having the expressly claimed water content for its disclosed bone-related therapeutic utility represents no patentably distinct invention. Instant claim 3 is therefore not patentably distinct from reference claims 1, 3, and 13.
Instant claim 4 further requires that the complex coacervate have a diameter of at least 500 nm in its shortest dimension. Reference claim 4 expressly claims that same dimensional limitation. The dependent limitation therefore identifies an expressly claimed physical embodiment of the same LF/OPN coacervate rather than a different coacervate or different therapeutic principle. Instant claim 4 is therefore not patentably distinct from reference claims 1, 4, and 13.
Instant claim 5 further requires a zeta potential within −15 to +15 mV. Reference claim 5 expressly claims the same zeta-potential range for the LF/OPN complex coacervate. Selection of that expressly claimed embodiment for the bone-related therapeutic use discussed for instant claim 1 constitutes an obvious variation of the invention already claimed in the reference application. Instant claim 5 is therefore not patentably distinct from reference claims 1, 5, and 13.
Instant claim 6 specifies that the complex coacervate is administered in a composition. Reference claim 13 broadly requires administration of an LF/OPN complex and does not restrict the physical vehicle through which the complex is administered. The supporting disclosure expressly describes compositions comprising the claimed complex coacervate and administering the coacervate in nutritional compositions or supplements. Administration of the claimed therapeutic complex in a composition is therefore a directly contemplated embodiment of the “administering” step of reference claim 13 rather than a different therapeutic invention. A person of ordinary skill would have had reason to employ the claimed complex in one of the disclosed compositions to deliver the complex to the subject, with a reasonable expectation that the composition would perform its conventional delivery function. Instant claim 6 is therefore not patentably distinct from reference claims 1 and 13.
Instant claim 7 limits the composition to food compositions, pet-food compositions, drinks, nutritional formulas, or nutraceuticals. The disclosure supporting the claimed LF/OPN coacervate expressly contemplates food and beverage products, animal-food products, nutritional compositions, and nutritional supplements containing the complex. These vehicles are ordinary delivery embodiments of the same coacervate and do not alter its identity or asserted bone-related biological function. Selecting one of these expressly contemplated oral/nutritional vehicles for administration of the coacervate therefore would have been an obvious implementation of reference claims 1 and 13. Instant claim 7 is not patentably distinct.
Instant claim 8 limits the composition to an infant formula, starter infant formula, follow-on formula, baby food, infant cereal composition, growing-up milk, fortifier, or supplement. The supporting disclosure expressly identifies those product forms for compositions comprising the LF/OPN complex coacervate. The claimed alternatives consequently amount to selection from expressly contemplated embodiments of administration of the same claimed therapeutic coacervate, without a new active agent, mechanism, or unexpected property recited in instant claim 8. Instant claim 8 is therefore not patentably distinct from reference claims 1 and 13.
Instant claim 9 requires oral administration. Reference claim 13 broadly recites administration to a subject, and the supporting disclosure expressly identifies oral administration as a preferred route for the claimed complex coacervate. Selecting the expressly preferred oral route for the treatment method would have been an obvious implementation of the administration required by reference claim 13. Instant claim 9 is therefore not patentably distinct from reference claims 1 and 13.
Instant claim 10 requires administration at 100-10,000 mg/kg/day. The supporting disclosure expressly identifies 100-10,000 mg/kg/day as a dosage range for the claimed LF/OPN complex coacervate. Reference claim 13 broadly claims administration without specifying a narrower dose. Accordingly, instant claim 10 selects an expressly identified dosage embodiment falling within the claimed administration method. No criticality or unexpected property attributable to selecting that expressly disclosed range is recited in the claim. The claimed dosage thus constitutes an obvious species of the broader administration defined by reference claim 13, rather than a patentably distinct invention. Instant claim 10 is not patentably distinct from reference claims 1 and 13.
Instant claim 11 requires that administration increase bone growth and/or bone strength. Those effects correspond directly to the bone-related utility disclosed for the LF/OPN complex coacervate of reference claim 1, wherein the disclosure expressly states that the coacervate may increase bone growth and/or bone strength upon administration and describes increases in bone parameters including bone mineral density, cortical bone volume, force yield, and stiffness. The limitation therefore states the expressly disclosed biological result of administering the same claimed coacervate for its disclosed bone-related utility. Instant claim 11 is not patentably distinct from reference claims 1 and 13.
Instant claim 13 limits the subject to a juvenile, adolescent, child, or infant. The disclosure supporting the bone-related utility of reference claim 1 expressly identifies juveniles, adolescents, children, and infants as subjects for administration of the LF/OPN complex coacervate and particularly identifies infants and young children as appropriate populations. Thus, instant claim 13 merely selects expressly contemplated members of the broader subject population encompassed by reference claim 13. Selection of these disclosed pediatric populations for the disclosed bone-related use would have been an obvious species of the claimed therapeutic method. Instant claim 13 is therefore not patentably distinct.
Instant claim 14 limits the subject to an adult. The disclosure supporting the reference claims expressly states that the bone-related invention may be applied to adolescents or adults and expressly identifies adult and elderly subjects. Because reference claim 13 broadly encompasses administration to a “subject,” selection of an expressly contemplated adult subject does not establish a patentably distinct method. Instant claim 14 is therefore not patentably distinct from reference claims 1 and 13.
Instant claim 15 limits the subject to an animal. The disclosure supporting reference claim 1 expressly states that the subject may be a mammal, human, or animal and identifies pets and other animal species. Reference claim 13 likewise broadly claims administration to a “subject.” Selecting an expressly contemplated animal subject for administration of the same therapeutic LF/OPN complex therefore constitutes an obvious species of the broader claimed therapeutic invention. Instant claim 15 is not patentably distinct from reference claims 1 and 13.
In summary, the instant claims define no patentably distinct invention over claims 1-5 and 13 of the co-pending application. The instant claims merely recite administration and therapeutic use of the same lactoferrin/osteopontin complex coacervate already claimed in the co-pending application and expressly disclosed therein for bone development, bone growth, bone strength, bone healing, and treatment of bone disease. To overcome this rejection, the applicant my amend the claims to establish a patentable distinction or file a terminal disclaimer.
New Rejections
The following new rejections are made from the previous Office Correspondence dated 16 June 2026, as the applicant's amendment necessitated the new grounds of rejection presented below based on the amended/newly cited limitations.
Claim Rejections - 35 USC § 103
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-AlA 35 U.S.C. § 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AlA) 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.
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 and 16 are rejected under 35 U.S.C. § 103 as being unpatentable over Liu et al. (Assessment of bioactivities of the human milk lactoferrin-osteopontin complex in vitro. J Nutr Biochem. 2019 Jul;69:10-18; hereinafter “Liu”), in view of Cornish et al. (US-20030191193-A1, published 09 Oct 2003; hereinafter “Cornish”), and Poundarik et al. (US-20180280570-A1, published 04 Oct 2018; hereinafter “Poundarik”), as applied to claim 1 above, and in further view of Bovetto et al. (WO-2012045801-A1, published 12 Apr 2012; hereinafter “Bovetto”).
Instant claim 16 further limits the metabolic bone disorder of instant claim 1 to low bone density, osteopenia, rickets, osteomalacia, Paget’s disease of bone, hypophosphatasia, scurvy, or a combination thereof. Cornish discloses osteomalacia, rickets, osteopenia, and Paget’s disease among the bone-related disorders contemplated for treatment with LF (¶[0018]). Cornish also expressly teaches administration of LF to prevent or treat a bone-related disorder and attributes to LF the ability to stimulate skeletal growth and inhibit bone resorption (¶[0004], ¶[0009]). Cornish’s express disclosure of osteopenia, rickets, osteomalacia, and Paget’s disease supplies multiple claimed alternatives. For the reasons stated with respect to instant claim 1, it would have been obvious to administer the LF-OPN complex coacervate resulting from Liu and Bovetto for one of the expressly identified bone disorders taught by Cornish, with a reasonable expectation that the known LF bone activity would be retained when LF was delivered in the food-grade coacervate form. Instant claim 16 therefore would have been obvious.
Claims 1, 16 and 17 are rejected under 35 U.S.C. § 103 as being unpatentable over Liu et al. (Assessment of bioactivities of the human milk lactoferrin-osteopontin complex in vitro. J Nutr Biochem. 2019 Jul;69:10-18; hereinafter “Liu”), in view of Cornish et al. (US-20030191193-A1, published 09 Oct 2003; hereinafter “Cornish”), and in further view of, Poundarik et al. (US-20180280570-A1, published 04 Oct 2018; hereinafter “Poundarik”), and Bovetto et al. (WO-2012045801-A1, published 12 Apr 2012; hereinafter “Bovetto”), as for claims 1 and 16 above, in further view of Faienza et al. (Metabolic Bone Disease of Prematurity: Diagnosis and Management. Front Pediatr. 2019 Apr 12;7:143; hereinafter “Faienza”).
The limitations of instant claims 1 and 16 are taught by Liu in view of Cornish, Poundarik, and Bovetto as described above, however, do not explicitly teach the limitations of instant claim 17, depending from instant claims 1 and 16. The combination applied to instant claim 16 teaches administration of the LF-OPN complex coacervate for an expressly claimed metabolic bone disorder such as osteopenia or rickets.
Faienza teaches that metabolic bone disease of prematurity is particularly prevalent in preterm and very-low-birth-weight infants, with incidence increasing further in extremely-low-birth-weight infants (Abstract; Introduction). Faienza explains that premature interruption of placental calcium and phosphate transfer contributes to impaired bone mineralization and that clinical manifestations include rickets, fractures, and postnatal growth failure. Faienza additionally identifies intrauterine growth restriction as a recognized factor associated with increased risk for metabolic bone disease in preterm infants (section “Risk Factors”). Faienza thus supplies support for each of the principal patient-history categories recited by instant claim 17- preterm birth, low birth weight, and intrauterine growth restriction.
Thus, it would have been obvious to select such a subject for the bone-directed nutritional intervention of the base combination because Faienza identifies that population specifically as one suffering or at heightened risk from impaired skeletal mineralization, osteopenic/metabolic bone disease, rickets, and growth failure. The prior art itself identifies the claimed population by the bone deficit that Cornish’s LF treatment is intended to address.
A person having ordinary skill also would have had a reasonable expectation that an enterally administered bone-supportive nutritional composition could be used in this population. Faienza describes nutritional and enteral management as central to prevention and management of metabolic bone disease of prematurity, while Bovetto expressly teaches food-grade LF complex coacervates suitable for infants. Faienza is not relied upon as teaching LF, OPN, or LF-OPN coacervation, rather, it supplies the expressly recited patient population and the bone-related reason for selecting that population. Accordingly, instant claim 17 would have been obvious.
Claims 1, 16 and 18 are rejected under 35 U.S.C. § 103 as being unpatentable over Liu et al. (Assessment of bioactivities of the human milk lactoferrin-osteopontin complex in vitro. J Nutr Biochem. 2019 Jul;69:10-18; hereinafter “Liu”), in view of Cornish et al. (US-20030191193-A1, published 09 Oct 2003; hereinafter “Cornish”), and in further view of, Poundarik et al. (US-20180280570-A1, published 04 Oct 2018; hereinafter “Poundarik”), and Bovetto et al. (WO-2012045801-A1, published 12 Apr 2012; hereinafter “Bovetto”), as for claims 1 and 16 above, in further view of DeBoer and Denson (Delays in puberty, growth, and accrual of bone mineral density in pediatric Crohn's disease: despite temporal changes in disease severity, the need for monitoring remains. J Pediatr. 2013 Jul;163(1):17-22. Epub 2013 Mar 22; hereinafter “DeBoer”).
The limitations of instant claims 1 and 16 are taught by Liu in view of Cornish, Poundarik, and Bovetto as described above, however, do not explicitly teach the limitations of instant claim 18, depending from instant claims 1 and 16. The combination applied to instant claim 16 teaches administration of the LF-OPN complex coacervate for an expressly claimed metabolic bone disorder such as osteopenia or rickets.
Instant claim 18 requires, inter alia, an instant claim 16 subject who suffered growth stunting because of Crohn’s disease. DeBoer teaches that pediatric Crohn’s disease is associated with linear-growth failure, short stature, delayed growth/puberty, and deficient accrual of bone mineral density. In its discussion of bone mineral density, DeBoer reports that approximately 43-46% of children with Crohn’s disease had BMD z-scores below −1 standard deviation at diagnosis and discusses persistent deficiencies in bone accrual (Introduction; section “Bone Mineral Density”). Thus, the art connected the claimed growth-stunting etiology (i.e., pediatric Crohn’s disease) with a phenotype falling within instant claim 16, namely low bone density/osteopenic skeletal accrual. A person having ordinary skill, already motivated by Cornish to employ LF to stimulate skeletal growth and inhibit bone resorption, would have had reason to administer the orally deliverable LF-OPN coacervate of the base combination to a child with Crohn’s-associated growth failure and reduced bone accrual.
A reasonable expectation of success rests on the known bone-directed activity of LF and the known suitability of LF complex coacervates for nutritional administration, not on an assertion that DeBoer tested LF-OPN in Crohn’s disease. DeBoer is relied upon for the claimed patient subgroup and its known skeletal deficit. Crohn’s disease independently satisfies one expressly recited alternative. Accordingly, instant claim 18 would have been obvious.
Claims 1, 16 and 19 are rejected under 35 U.S.C. § 103 as being unpatentable over Liu et al. (Assessment of bioactivities of the human milk lactoferrin-osteopontin complex in vitro. J Nutr Biochem. 2019 Jul;69:10-18; hereinafter “Liu”), in view of Cornish et al. (US-20030191193-A1, published 09 Oct 2003; hereinafter “Cornish”), and in further view of, Poundarik et al. (US-20180280570-A1, published 04 Oct 2018; hereinafter “Poundarik”), and Bovetto et al. (WO-2012045801-A1, published 12 Apr 2012; hereinafter “Bovetto”), as for claims 1 and 16 above, in further view of Siegel et al. (Risk factors and surveillance for reduced bone mineral density in pediatric cancer survivors. Pediatr Blood Cancer. 2017 Sep;64(9). Epub 2017 Feb 24; hereinafter “Siegel”).
The limitations of instant claims 1 and 16 are taught by Liu in view of Cornish, Poundarik, and Bovetto as described above, however, do not explicitly teach the limitations of instant claim 19, depending from instant claims 1 and 16. The combination applied to instant claim 16 teaches administration of the LF-OPN complex coacervate for an expressly claimed metabolic bone disorder such as osteopenia or rickets.
Instant claim 19 further requires that the subject of instant claim 16 have been treated with chemotherapy drugs and/or corticosteroids. Siegel teaches that survivors of childhood cancer are at risk for reduced bone mineral density as a consequence of disease and treatment and discusses the Children’s Oncology Group surveillance recommendations for survivors exposed to bone-damaging therapies. The identified treatment-related risk exposures include corticosteroids and methotrexate, a chemotherapeutic agent, among populations screened for reduced BMD (Abstract and risk-factor/surveillance discussion).
Cornish independently identifies glucocorticoid-induced osteoporosis among LF-treatable bone disorders (¶[0018]), corroborating that the adverse skeletal consequences of corticosteroid treatment were known in the LF bone-treatment art. Instant claim 16 itself encompasses the broader phenotype “low bone density” and osteopenia. Accordingly, one of ordinary skill would have had reason to select a patient with low bone density or osteopenia following corticosteroid or chemotherapeutic exposure for administration of a composition already suggested by the base references for stimulating skeletal growth and inhibiting bone resorption. The claimed treatment history identifies a known high-risk bone-loss population rather than a mechanistically unrelated subgroup. Siegel supplies the known relationship between the claimed prior-treatment history and the claimed low-BMD skeletal phenotype, the base combination supplies the bone-directed LF-OPN coacervate treatment. Accordingly, instant claim 19 would have been obvious.
Claim 20 is rejected under 35 U.S.C. § 103 as being unpatentable over Liu et al. (Assessment of bioactivities of the human milk lactoferrin-osteopontin complex in vitro. J Nutr Biochem. 2019 Jul;69:10-18; hereinafter “Liu”), in view of Cornish et al. (US-20030191193-A1, published 09 Oct 2003; hereinafter “Cornish”), and in further view of, Poundarik et al. (US-20180280570-A1, published 04 Oct 2018; hereinafter “Poundarik”), and Bovetto et al. (WO-2012045801-A1, published 12 Apr 2012; hereinafter “Bovetto”).
Instant claim 20 recites a method of improving bone development and growth in a juvenile, adolescent, child, or infant by administering a complex coacervate comprising LF and OPN. Liu teaches the specific LF-OPN protein pair and the improved digestive stability and intestinal interaction resulting from formation of the LF-OPN complex (p. 10, Abstract; p. 11, § 2.1; pp. 13-16). Bovetto teaches converting LF and an acidic protein into a food-grade complex coacervate under defined conditions and expressly states that such compositions are suitable for children and infants, including infants younger than twelve months (p. 11, ll. 3-8). Cornish teaches that LF stimulates skeletal growth and inhibits bone resorption (¶[0004]). Poundarik corroborates OPN’s recognized involvement in bone formation and mineralization.
It would have been obvious to apply Bovetto’s known LF complex-coacervation technique to Liu’s specifically identified acidic LF-binding partner OPN and administer the resulting edible complex to the pediatric subjects expressly contemplated by Bovetto for the skeletal-growth purpose taught by Cornish. The combination amounts to application of a known protein-coacervation technique to a protein pair already known to interact by the relevant electrostatic mechanism, followed by use of the resulting nutritional composition for a biological effect expressly taught for LF.
The skilled artisan would have had a reasonable expectation of success in doing so because Liu demonstrates the LF-OPN association, Bovetto provides operative LF coacervation conditions and pediatric nutritional use, and Cornish supplies experimental and therapeutic evidence that LF promotes skeletal growth. The references therefore provide more than a generalized invitation to explore an unpredictable field. Accordingly, instant claim 20 would have been obvious.
Claims 20 and 21 are rejected under 35 U.S.C. § 103 as being unpatentable over Liu et al. (Assessment of bioactivities of the human milk lactoferrin-osteopontin complex in vitro. J Nutr Biochem. 2019 Jul;69:10-18; hereinafter “Liu”), in view of Cornish et al. (US-20030191193-A1, published 09 Oct 2003; hereinafter “Cornish”), and in further view of, Poundarik et al. (US-20180280570-A1, published 04 Oct 2018; hereinafter “Poundarik”), and Bovetto et al. (WO-2012045801-A1, published 12 Apr 2012; hereinafter “Bovetto”), as for claim 20 above, in further view of Faienza et al. (Metabolic Bone Disease of Prematurity: Diagnosis and Management. Front Pediatr. 2019 Apr 12;7:143; hereinafter “Faienza”).
The limitations of instant claim 20 is taught by Liu in view of Cornish, Poundarik, and Bovetto as described above, however, does not explicitly teach the limitations of instant claim 21, depending from instant claim 20.
As discussed for instant claim 17, Faienza expressly identifies prematurity, very low birth weight, and intrauterine growth restriction in connection with metabolic bone disease, impaired skeletal mineralization, rickets, fractures, and/or growth failure (Abstract; Introduction; “Risk Factors”). Once the combined teachings of Liu, Bovetto, and Cornish suggested administration of an LF-OPN coacervate to improve skeletal development and growth in an infant or child, Faienza would have provided a specific reason to select a preterm, low-birth-weight, or growth-restricted infant because those infants were already recognized as a population in whom deficient bone mineralization and postnatal skeletal growth were clinically important problems. Bovetto additionally establishes that food-grade LF complex coacervates are suitable for administration to infants.
A person having ordinary skill would have had a reasonable expectation that a nutritional intervention directed to skeletal growth could be administered to such infants because enteral nutritional management was already a principal component of management and prevention of metabolic bone disease of prematurity. Faienza’s relevance is the specifically claimed patient selection and the known skeletal reason for that selection. The Crohn’s-disease and corticosteroid/chemotherapy evidence applied above to instant claims 18 and 19 independently corroborates portions of alternatives (iii) and (iv), but those references need not be incorporated into this particular ground. Accordingly, instant claim 21 would have been obvious.
Claim Rejections – Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
Claims 16-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 13 of co-pending U.S. Application No. 18/720,338 (reference application). Although the respective claims are not identical, the newly presented claims define expressly disclosed disease species, patient populations, or therapeutic utilities of the LF/OPN complex coacervate already claimed in the reference application and therefore are not patentably distinct for the reasons below. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Instant claim 16 limits the metabolic bone disorder of instant claim 1 to low bone density, osteopenia, rickets, osteomalacia, Paget’s disease of bone, hypophosphatasia, scurvy, or a combination thereof. The disclosure supporting the bone-disease utility of reference claim 1 expressly characterizes metabolic bone disease as including low bone density, osteoporosis, osteopenia, rickets, osteomalacia, Paget’s disease of bone, hypophosphatasia, scurvy, and osteitis fibrosa cystica.
Instant claim 16 therefore does not identify an unmentioned disease class or a newly discovered use. It selects disease species expressly identified as metabolic bone disorders for which the claimed LF/OPN coacervate is disclosed as useful. At minimum, each individually recited alternative falling within claim 16 corresponds to an expressly identified metabolic-bone-disease embodiment. A person of ordinary skill would have regarded treatment of those expressly identified diseases with the claimed coacervate as an obvious implementation of its disclosed bone-disease utility. The additional alternative permitting a combination of such disorders does not render the claim patentably distinct because it does not require a different coacervate, dosage mechanism, or therapeutic principle. Instant claim 16 is therefore not patentably distinct from reference claims 1 and 13.
Instant claim 17 further requires that the subject was born preterm, born with low birth weight, or experienced intra-uterine growth retardation. The reference disclosure specifically identifies metabolic bone disease as frequent in preterm and/or low-birth-weight infants and infants suffering suboptimal intra-uterine nutrition, and expressly identifies infants and children born preterm, born with low birth weight, or having experienced intra-uterine growth retardation as particularly suitable recipients of the LF/OPN coacervate bone-related therapy. Instant claim 17 therefore selects the precise risk populations identified for the disclosed utility of the claimed coacervate. Such selection would have been an obvious species of the claimed therapeutic invention and does not establish patentable distinctness.
Instant claim 18 further limits the subject to one suffering growth stunting because of malnutrition, anorexia, Crohn’s disease and/or celiac disease. The supporting disclosure expressly identifies infants and children suffering growth retardation due to malnutrition and/or disease and specifically identifies growth stunting caused by malnutrition or associated with anorexia, Crohn’s disease, and/or celiac disease. These are therefore not newly identified patient categories; they are expressly contemplated populations for the bone-related use of the claimed LF/OPN coacervate. Selecting those populations for treatment would have been an obvious variant of the invention defined by reference claims 1 and 13. Instant claim 18 is not patentably distinct.
Instant claim 19 requires that the subject has been treated with chemotherapy drugs and/or corticosteroids. The supporting disclosure expressly identifies subjects treated with drugs leading to malabsorption, anorexia, and/or metabolic bone disease, specifically including chemotherapy drugs and corticosteroids, as populations for application of the claimed LF/OPN coacervate. Thus, the claimed patient-selection criterion is expressly associated with the disclosed bone-related therapeutic utility of the composition already claimed in reference claim 1. Selecting such subjects therefore does not define a patentably distinct invention. Instant claim 19 is not patentably distinct from reference claims 1 and 13.
Instant claim 20 recites a method of improving bone development and growth by administering an LF/OPN complex coacervate to a juvenile, adolescent, child, or infant. Reference claim 1 claims the identical LF/OPN complex coacervate. The utility supporting that claim expressly identifies promotion of bone development and growth as uses of the claimed coacervate and expressly identifies juveniles, adolescents, children, and infants as suitable subjects. Consequently, instant claim 20 is directed to the use of the already-claimed composition for an expressly disclosed utility in an expressly disclosed population, which does not provide a patentable distinction. A person of ordinary skill would have had reason to administer the reference-claimed coacervate to the expressly identified pediatric populations to obtain the expressly identified improvement in bone development and growth, with a reasonable expectation of obtaining the disclosed bone-development effect. Instant claim 20 is therefore not patentably distinct from reference claim 1 and is further consistent with the administration method broadly claimed in reference claim 13.
Instant claim 21 further limits the juvenile, adolescent, child, or infant of instant claim 20 to: (i) subjects born preterm, with low birth weight, or having experienced intra-uterine growth retardation; (ii) subjects suffering growth stunting because of malnutrition; (iii) subjects suffering growth stunting because of anorexia, Crohn’s disease, and/or celiac disease; and/or (iv) subjects suffering growth stunting because of chemotherapy drugs and/or corticosteroids.
Each of these population categories is expressly identified in the disclosure supporting the bone-related utility of the LF/OPN coacervate claimed in reference claim 1. The reference identifies infants and children born preterm, with low birth weight, or after intra-uterine growth retardation; subjects having growth stunting from malnutrition; subjects with anorexia, Crohn’s disease, or celiac disease; and subjects treated with chemotherapy drugs or corticosteroids leading to growth or metabolic-bone consequences. Instant claim 21 therefore merely combines expressly identified patient-selection criteria with the same expressly disclosed bone-development use of the same claimed LF/OPN coacervate.
Nothing in instant claim 21 requires a structurally different coacervate, a different mechanism of administration, or an unexpected therapeutic response peculiar to these patient groups. Thus, instant claim 21 is not patentably distinct from reference claims 1 and 13.
In summary, the pending claims of Application No. 18/720,338 define the LF/OPN complex coacervate itself, its relevant structural/compositional species, and administration of an LF/OPN complex for treatment or prevention of metabolic disorders. The portions of the reference disclosure discussed above are considered only insofar as they support, identify the utility of, and permit proper construction of those claimed inventions. Because the cited reference application remains co-pending, these are provisional nonstatutory double patenting rejections. A timely terminal disclaimer satisfying 37 C.F.R. § 1.321 may obviate a proper nonstatutory double patenting rejection where the applicable common-ownership requirements are satisfied, or, alternatively, the applicant may establish that the rejected claims are patentably distinct from the reference claims.
Response to Arguments
Applicant Arguments/Remarks of the reply, filed 15 September 2026, have been fully considered.
Bovetto supplies the complex-coacervation teaching of lactoferrin with an oppositely charged protein having an isoelectric point below pH 7 and states, broadly, that any other protein with an isoelectric point lower than pH 7.0 will produce suitable coacervates. Bovetto further teaches coacervates having diameters greater than 500 nm and ζ-potentials between +15 and -15 mV and supplies operative pH, ionic strength, protein concentration, temperature, and mixing-ratio windows.
The suitability of OPN for the Bovetto teaching is not speculative. Before the effective filing date, Yamniuk et al. had characterized OPN as an anionic protein (pI about 3.6), LF as a cationic protein (pI about 9), and demonstrated biologically relevant high-affinity interaction in which multiple LF molecules bind a single OPN molecule. Cornish supplies the established bone-related activity of lactoferrin. Cornish teaches that lactoferrin stimulates skeletal growth and inhibits bone resorption and expressly proposes its use for preventing and treating bone disorders. Poundarik provides additional evidence of the established role of OPN in bone biology, teaching that OPN participates in bone formation and tissue mineralization.
Thus, a person of ordinary skill in the art would have been motivated to combine these teachings to deliver both bone-active proteins in a protected, bioavailable form. The motivation is to improve stability, bioavailability, and delivery of LF and OPN for bone health by forming the LF-OPN complex coacervate taught by Liu. The skilled artisan would have had a reasonable expectation of success because Liu demonstrates that the LF-OPN complex forms spontaneously and is stable, and Cornish and Poundarik establish the bone-related activities of the individual proteins. Hence, the rejection does not depend on finding the entire claimed invention in any single reference. The relevant inquiry is what the combined teachings would have suggested to one of ordinary skill (see In re Keller, 642 F.2d 413, 208 USPQ 871 (Cust. Ct. 1981)). Obviousness does not require bodily incorporation of one reference's particular embodiment into another.
The applicant argues that Cornish teaches “pure” lactoferrin, defined as lactoferrin free from other biological macromolecules, and therefore would have discouraged the skilled artisan from combining lactoferrin with osteopontin. The argument is not persuasive. Cornish's definition of “pure” describes the purity of the lactoferrin polypeptide preparation, not a requirement that lactoferrin be administered as the sole macromolecule in the ultimate pharmaceutical or nutritional composition. Cornish defines its purified starting polypeptide in that manner. But Cornish explicitly teaches nutraceutical and pharmaceutical compositions containing that lactoferrin and further permits other bone-enhancing agents and also states that the method may concurrently administer another bone-enhancing agent. Cornish additionally contemplates nutritional compositions containing other nutrients, including other proteins.
More fundamentally, Cornish is not relied upon to teach the physical form of the claimed LF-OPN complex. Liu identifies the LF-OPN pair, and Bovetto teaches formation of lactoferrin complex coacervates with acidic proteins. Cornish is relied upon for the known bone anabolic/anti-resorptive utility of lactoferrin. The applicant's argument therefore rests on bodily incorporating Cornish's particular purified-LF embodiment into Liu, which is not the governing obviousness inquiry. Cornish provides a reason to use LF for bone, and Liu provides the reason to complex LF with OPN for stability and delivery. Cornish does not criticize, discredit, or discourage use of lactoferrin in combination with other components. Accordingly, the “pure” terminology does not amount to a teaching away (see In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004)).
The articulated reason for the proposed combination is not merely that the references could theoretically be combined. Liu had already identified the particular LF-OPN pair and demonstrated enhanced digestive stability and intestinal-cell uptake of the complex. Bovetto taught a known technique for converting lactoferrin plus oppositely charged acidic proteins into food-grade complex coacervates and further taught that coacervation can affect digestion kinetics and biological response. A skilled artisan therefore would have had reason to apply Bovetto's established lactoferrin-coacervation technique to the specifically identified, electrostatically complementary LF-OPN pair of Liu in order to obtain a stable, orally administrable protein-rich coacervate having controlled digestion/bioavailability characteristics. The known skeletal-growth and anti-resorptive activity of LF taught by Cornish, together with the established bone-mineralization role of OPN taught by Poundarik, supplied a reason to investigate and employ that LF-OPN coacervate for bone-related administration.
That rationale is consistent with KSR International Co. v. Teleflex Inc., 550 U.S. 398, 417-18 (2007), wherein a known technique applied to a known composition ready for improvement can support obviousness where the record explains why the variation would have been predictable. The reasonable-expectation inquiry likewise does not demand certainty or conclusive clinical proof. It requires a reasonable likelihood that the proposed modification will work for its intended purpose (see MPEP §2143.02; In re O'Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988)). Here, Bovetto does substantially more than document complex coacervation as a promising field. Bovetto identifies the relevant charge relationship and provides concrete pH, protein-concentration, ionic-strength, temperature, and mixing-ratio parameters. OPN satisfies Bovetto's acidic-protein criterion, while Liu/Yamniuk already demonstrate direct high-affinity LF-OPN electrostatic association. The proposed modification therefore is not an unfocused search among innumerable possibilities.
The applicant's Figure 4 evidence has been fully considered as objective evidence relevant to obviousness. The evidence is probative. It compares the LF-OPN coacervate with an LF-OPN soluble complex and an LF-OPN blend and therefore supports the applicant's proposition that physical form can affect bone-related outcomes. The evidence nevertheless does not, on the present record, overcome the prima facie case for the breadth of amended claim 1.
First, the tested animals were healthy wild-type mice rather than animals having, or experimentally placed at risk for, a metabolic bone disorder. The study therefore shows an effect on normal bone development/growth, not a reduction in occurrence, duration, frequency, or severity of any claimed metabolic bone disorder. This substantially limits the nexus of Figure 4 to the disease-treatment/prophylaxis scope of claim 1. Second, the experiment employed a particular bovine LF-OPN preparation at 1250 mg/kg/day and 20% w/v, whereas claim 1 imposes no protein ratio, dose, concentration, coacervation pH, ionic strength, particle-size, or ζ-potential limitation. Objective evidence must be reasonably commensurate in scope with the claims (see In re Clemens, 622 F.2d 1029, 1036 (CCPA 1980); In re Peterson, 315 F.3d 1325, 1329-31 (Fed. Cir. 2003); MPEP §716.02(d).
Third, proof that one embodiment performs better than another does not by itself establish unexpectedness. The question is whether the magnitude or character of the difference would have been unexpected to the skilled artisan in view of the prior art. MPEP §716.02 explains that the asserted results must be shown to be unexpected and of statistical and practical significance, and the evidence is then weighed with the evidence supporting obviousness. Bovetto had already taught that changing complex-coacervate composition and size affects digestion kinetics and biological response. Thus, some biological difference attributable to physical form was not itself contrary to the prior-art teaching.
Figure 4 panels A and C bear an asterisk associated with p<0.05, whereas panel B for trabecular BMD appears to be labeled p<0.08. Accordingly, panel B itself does not demonstrate significance at the conventional p<0.05 threshold. Thus, Figure 4 is accorded probative weight, but its limited disease nexus, limited experimental scope, and absence of evidence establishing that the observed magnitude of superiority was unexpected are insufficient, on the present record, to outweigh the evidence supporting obviousness of broad claim 1. The data do not show that the claimed coacervate produces unexpected results across the full scope of metabolic bone disorders, subject populations, or dosages.
The applicant argues that Poundarik neither treats a metabolic bone disorder nor teaches the claimed LF-OPN coacervate. That observation is correct but does not identify the role for which Poundarik is relied upon. Poundarik teaches osteopontin's established participation in bone formation and tissue mineralization and describes OPN-containing materials for mineralization within a subject. Poundarik is not relied upon to supply the LF-OPN complex, the coacervate form, or the metabolic-bone-disorder treatment limitation. Those aspects arise from the combined teachings of Liu, Bovetto, and Cornish. The fact that Poundarik alone does not disclose the claimed method therefore does not defeat the rejection. A reference need not explicitly address every condition recited in the claim to be relevant to bone health.
The applicant similarly argues that Bovetto does not itself disclose administering an LF-OPN coacervate to treat a metabolic bone disorder. Again, Bovetto is not relied upon for that proposition. Bovetto teaches the physical coacervate technology missing from Liu- lactoferrin coacervation with an acidic protein, the relevant physicochemical conditions, particle size, near-neutral ζ-potential, modulation of digestion, oral/enteral food use, and administration to children and infants. Liu supplies OPN as the particular acidic LF-binding partner, Cornish supplies lactoferrin's bone therapeutic use, and Poundarik corroborates OPN's bone-related functionality. The applicant's argument therefore does not address the collective technical proposition underlying the rejection. Combining Bovetto’s formulation parameters with Liu’s LF-OPN complex is routine optimization of result-effective variables.
The applicant's assertion that new claims 16-21 are patentable “for substantially the same reasons” has been considered but does not establish patentability merely because those limitations are expressly supported in the specification. The specification does in fact contain express textual support for the preterm/low-birth-weight/IUGR, malnutrition, Crohn's/celiac disease, chemotherapy/corticosteroid, and pediatric subject limitations. Written-description support, however, is distinct from patentability over the prior art.
For claim 16, the applicant cannot persuasively characterize Cornish as merely “osteoporosis-focused.” Cornish expressly identifies osteomalacia, rickets, osteopenia, Paget's disease, and glucocorticoid-induced osteoporosis, among numerous bone disorders. Thus, several express alternatives of claim 16 were already specifically identified by Cornish. Claim 19's corticosteroid alternative is likewise not divorced from Cornish's teaching, because Cornish specifically identifies glucocorticoid-induced osteoporosis as a bone disorder susceptible to lactoferrin treatment.
As to claim 20, the contention that the claimed juvenile/adolescent/child/infant population is categorically distinct from the applied art is also unpersuasive. Cornish expressly teaches stimulation of skeletal growth, while Bovetto teaches administration of lactoferrin complex coacervates to children, including infants. Liu itself concerns LF and OPN as human-milk proteins and their potential nutritional relevance. Figure 4 has a stronger nexus to claim 20 than to amended claim 1 and therefore should be given correspondingly greater weight, but the claim remains substantially broader than the single bovine-protein/mouse/dose embodiment tested.
For claims 17, 18, and 21, the prior Liu/Cornish/Poundarik/Bovetto combination, as previously articulated, does not itself clearly establish each of the specific historical/risk-population limitations (e.g., preterm birth, low birth weight, IUGR, or growth stunting specifically resulting from malnutrition, anorexia, Crohn's disease, or celiac disease). Therefore additional prior art addressing these additional limitations are provided in the present rejections, as outlined above.
The applicant requests that the provisional nonstatutory double-patenting rejection be withdrawn or held in abeyance until the claims are otherwise allowable because both sets of claims may change. The co-pending application presently contains claim 1 to the LF-OPN complex coacervate, claims 2-5 to the same protein-content, water-content, size, and ζ-potential limitations, and claim 13 to administering an LF-OPN complex for treating or preventing metabolic disorders. Accordingly, the applicant's request to hold the provisional rejection in abeyance is denied.
In summary, the applicant's §103 arguments and Figure 4 evidence have been considered. The evidence is probative but does not, for the reasons set forth above, overcome the prima facie showing as to the breadth of claim 1. The obviousness analysis is clarified to rely on Liu for the specific LF-OPN complex, Bovetto for LF-acidic-protein complex coacervation, Cornish for lactoferrin's bone-related therapeutic activity, and Poundarik for OPN's established bone-mineralization function. The provisional nonstatutory double-patenting rejection is maintained and will not be held in abeyance.
Conclusion
No claims are allowed.
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 nonprovisional extension fee (87 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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/RL Scotland/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
