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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 14, 2026 has been entered.
Election/Restrictions
To summarize the current election, the applicant elected Group I, without traverse.
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.
Claims 1, 118-119, 125-128, and 133-135 are rejected under 35 U.S.C. 103 as being unpatentable over Islan et al. Islan et al. (previously cited) in view of Kunjukunju et al. (previously cited), Kwon et al. (US PGPub No.2002/0051821), Melvik et al. (US PGPub No. 2006/00159823), Dowling et al. (previously cited), and Smrdel et al. (previously cited).
Islan et al. teach microspheres composed of alginate encapsulating alginate lyase and an antibiotic drug to provide both compounds to a subject (see abstract; instant claim 133). The microspheres are generated via ionic crosslinking of droplets of an alginate solution in a solution of calcium chloride in a 50:50 mixture of water and propylene glycol, thereby incorporating propylene glycol into the microspheres entrapping the alginate lyase in the crosslinked alginate (see page 1240 first column first paragraph and page 1242 first column last partial paragraph-page 1243 first column and figure 1; instant claims 125-126 and 134-135). There is no clear distinction between divalent calcium ions acting as crosslinking metal divalent cations and divalent calcium ions that are alginate lyase inhibitors, thus the presence of divalent calcium ions in the particles acting as crosslinking metal ions meets both limitations (see instant claim 126 and 128). The presence of the propylene glycol improved the sphericity and eliminated cracking of the particles when freeze dried (see page 1242 first column last partial paragraph-page 1243 first column and figure 1; instant claim 1). The propylene glycol containing microspheres are shown to have a diameter of 580 mm (see figure 1c; instant claims 1 and 127). They detail that at least 90% of the feed alginate lyase was incorporated into the microspheres starting from a 2 wt% 120 kDa alginate solution with 40 U/ml alginate lyase feed stock (see page 120 first column first paragraph and page 1246 first column first column first partial paragraph; instant claim 1). The bulk mixture of alginate and alginate lyase yields alginate lyase that is temporarily “entrapped” by the crosslinked alginate molecules (see instant claim 135). Release of the contained drug is detailed to occur over a few hours at 7.4 pH in the presence of auto-degradation by the lyase (see page 1245 second column first partial paragraph and figures 3 and 5). The monomer ratio of the alginate is not detailed by Islan et al. and the alginate molecular weight is not within the instantly claimed range.
Kunjukunju et al. teach alginate particles crosslinked with calcium ions that include native alginate lyase or an aggregate of alginate lyase stabilized with ammonium sulfate to act as controlled release carriers for drugs (see page 178 first column first paragraph and second column second full paragraph and page 183 first column last full paragraph). The alginate has a molecular weight of 80,000 to 120,000 Da and a ratio of M units to G units of 61:39 which meets the limitations of about 60:40 (see page 177 first column first full paragraph; instant claim 1). The native alginate lyase encapsulating particles degrade (self-degrading) in about 5 days (6 days) (see page 182 second column last partial paragraph-page 183 first column first full paragraph; instant claim 1).
Kwon et al. teach alginate particles that encapsulate and deliver protein or small molecule drugs and may be freeze dried (see abstract, paragraph 48 example 1). They discuss useful varieties of alginate for this purpose. Specifically, they teach that low G varieties are appropriate and can have a G content of 25 to 35% which corresponds to a 65:35 to 75:25 M to G ratio range (see paragraph 47; instant claims 1 and 119).
Melvik et al. teach ionically crosslinked alginate gel materials envisioned to deliver drug and proteins (see abstract and paragraphs 44, 51, and 64). They detail that the alginate has a molecular weight that ranges from 1 to 1000 kDa, where a range of 100 to 1000 kDa is also envisioned (see paragraph 42; instant claims 1 and 118). The ratio of M to G units in the polymer controls its biodegradation, where a lower G proportion yields a more biodegradable gel (see paragraph 42). An example employs an alginate with an M to G ratio 56:44, which meets the limitations of about 55:45, and a 220 kDa molecular weight (see example 25; instant claim 1).
Dowling et al. teach self degrading microcapsules where the capsules encapsulate an enzyme for the polysaccharide that composes its shell (see abstract). They detail that the size can be adjusted downward by making smaller droplets of capsule material during production (see page 7995 first column first partial paragraph). Degradation times that span from minutes to hours are detailed and Dowling et al. note that the time shortened with increasing enzyme concentration (see page 7994 first column first partial paragraph, page 7995 second column and figure 3). As an example, they show spherical microcapsules sized at about 2750 mm, based on the scale bar, with 1.5 U/ml enzyme in the lumen (see figure 2). This corresponds to approximately 5.2 mU enzyme per particle (as calculated by the examiner).
Smrdel et al. discuss the desire for uniformity in shape amongst calcium crosslinked alginate particles employed for drug delivery (see abstract and page 84 first full paragraph). They go on to detail parameters involved in dropwise particle production techniques that directly influence sphericity such as the temperature of the calcium ion bath and hardening time (see figure 1). Here sphericity values of about 0.9 are achieved at higher hardening times (e.g., 30 minutes) and higher bath temperatures (e.g., 40⁰C).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ an alginate in the microspheres of Islan et al. that has a monomer ratio already envisioned to be useful for drug delivery and facilitates biodegradability, given the intended auto-degradation outcome due to its loaded lyase. Kunjukunju et al., Kwon et al., and Melvik et al. detail such a ratio where Kunjukunju et al. also teach the utility of low G rations for alginate used in particles for drug delivery controlled via alginate lyase. Thus, it would have been obvious to employ a 75:25 to 56: 44 M:G ratio range for alginate, as taught by the trio of teachings, for the microspheres of Islan et al. This modification would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome. It additionally would have been obvious to select an alginate molecular weight known to be suitable for drug delivery in light of Melvik et al. and apply their range of 100 to 1000 kDa or their exemplary polymer with a 220 kDa size. This modification would have been obvious because their molecular weight range embraces that of Islan et al. and also as the simple substitution of one known element for another in order to yield a predictable outcome. The resulting products provide an overlapping range of molecular weights and M to G ratios with those instantly claimed, thereby rendering the claimed ranges obvious. “In 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)” (see MPEP 2144.05). The result is the claimed components in the claimed configuration; thus their associated functionality of degradation duration should follow. According to MPEP 2145II, mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). In addition, the fact that an inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Further, optimization of the degradation rate of the microspheres via enzyme concentration/amount per particle would have been obvious as matter of routine experimentation in light of Dowling et al. (see instant claim 1). Additionally, it also would have been obvious to prepare the microspheres employing production parameters that yield particles with a higher sphericity, so as to have uniformity for use in drug delivery. This modification would have been obvious in light of Smrdel et al. as the application of the same technique to a similar product in order to yield the same improvement. The parameters and sphericity outcome are result effective variables and therefore are obvious to optimize as a matter of routine experimentation. Therefore claims 1, 118-119, 125-128, and 133-135 are obvious over Islan et al. in view of Kunjukunju et al., Kwon et al., Melvik et al, Dowling et al., and Smrdel et al.
Claims 1, 118-119, 125-128, and 132-135 are rejected under 35 U.S.C. 103 as being unpatentable over Islan et al. in view of Kunjukunju et al., Kwon et al., Melvik et al, Dowling et al., and Smrdel et al. as applied to claims 1, 118-119, 125-128, and 133-135 above, and further in view of Boyan et al. (previously cited).
Islan et al. in view of Kunjukunju et al., Kwon et al., Melvik et al, Dowling et al., and Smrdel et al. render obvious the limitations of instant claims 1, 118-119, 125-128, and 133-135. The presence of oxidized alginate in the microspheres is not detailed.
Boyan et al. teach alginate microspheres for cell encapsulation that generate desirable bioactive proteins for therapeutic use (see paragraphs 10-12). The microspheres are generated via ionic crosslinking of size controlled droplets of an alginate solution in a solution of calcium chloride (see paragraph 69 and examples 1-2). Additionally, the alginate may have a molecular weight of 50,000 to 400,000 Da (see paragraphs 158 and 190). They teach to include alginate lyase so as to induce controlled degradation for biological applications and note that the rate of degradation increases with increasing concentration (see paragraphs 23-26, 66, 69, 172, and 176, examples 26-27, and figure 15). Thus the concentration of alginate lyase, on a mass or per particle basis, is a result effective variable. Boyan et al. further teach that including oxidized alginate permits added control over the rate of degradation, where the process can be expedited due to its presence and the additional hydrolysis susceptible sites oxidation introduced (see paragraphs 26, 169, and 234; instant claim 132).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add oxidized alginate as taught by Boyan et al. into the particles of Islan et al. in view of Kunjukunju et al., Kwon et al., Melvik et al, Dowling et al., and Smrdel et al. so as to modulate their rate of degradation. This modification would have been obvious as the application of the same technique to a similar product to yield the same improvement. Therefore claims 1, 118-119, 125-128, and 132-135 are obvious over Islan et al. in view of Kunjukunju et al., Kwon et al., Melvik et al, Dowling et al., Smrdel et al., and Boyan et al.
Claims 1, 118-119, 125-128, 130, and 133-135 are rejected under 35 U.S.C. 103 as being unpatentable over Islan et al. in view of Kunjukunju et al., Kwon et al., Melvik et al, Dowling et al., and Smrdel et al. as applied to claims 1, 118-119, 125-128, and 133-135 above, and further in view of Santagapita et al. (Biomacromolecules 2011 12(9):3147-3155) and Isobe et al. (US PGPub No. 2009/0123449).
Islan et al. in view of Kunjukunju et al., Kwon et al., Melvik et al, Dowling et al., and Smrdel et al. render obvious the limitations of instant claims 1, 118-119, 125-128, and 133-135, where propylene glycol is included in the alginate microspheres. The presence of sorbitol, ethylene glycol, or glycerol (glycerin) is not detailed.
Santagapita et al. teach including an enzyme stabilizer, such as trehalose, along with an enzyme encapsulated in an alginate particle to stabilize the enzyme during drying (see abstract and page 3148 first column first full paragraph-second column first partial paragraph and supporting information table S4).
Isobe et al. teach of the inclusion of enzyme stabilizers in a composition that provides enzymes, such as alginate lyase (see abstract paragraphs 34 and 48). The stabilizers are envisioned to include sorbitol and polyols such as propylene glycol, ethylene glycol, glycerol (see paragraph 48).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add sorbitol, ethylene glycol, or glycerin into the alginate microspheres of Islan et al. in view of Kunjukunju et al., Kwon et al., Melvik et al, Dowling et al., and Smrdel et al. so as to protect the contained alginate lyase. This modification would have been obvious as the application of the same technique to a similar product to yield the same improvement. Since an enzyme stabilizer is already present in the particles, the addition is also obvious as the combination of two components known for the same purpose. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) see (MPEP 2144.06). Therefore claims 1, 118-119, 125-128, 130, and 133-135 are obvious over Islan et al. in view of Kunjukunju et al., Kwon et al., Melvik et al, Dowling et al., Smrdel et al., Santagapita et al., and Isobe et al.
Response to Arguments
Applicant's arguments filed May 14, 2026 have been fully considered. In light of the amendment to the claims, the previous grounds of rejection are withdrawn. New grounds of rejection are detailed to address the new claim limitations and new combinations of previous claim limitations.
Conclusion
No claim is allowed.
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/CARALYNNE E HELM/Examiner, Art Unit 1615
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