DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment filed May 14, 2026, has been received and entered.
Claims 10-15 are cancelled.
Claims 1-9 and 16-19 are pending. Claims 16-19 are withdrawn.
Claims 1-9 are examined on the merits.
Notice Re: Prior Art Available Under Pre-AIA and AIA
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-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) 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.
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.
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 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Rescigno (WO 2018/024833. Listed on IDS filed 6/3/22) in view of Chapin (US 2010/0311688), Gelsomino (WO 2016/092513. Previously cited), and Gao (Eye & Contact Lens. May 2018. 44(3): 200-201), as evidenced by Hatti-Kaul (FEMS Microbiology Letters. 2018. 365: fny213. 20 pages. Published August 30, 2018. Previously cited) and Reid (US 2007/0036776).
Rescigno discloses a “fermented product of Lactobacillus species (postbiotic)” used for the generation of an eyedrop formulation to protect the eye mucosa from infections and allergic reactions and subsequent conjunctivitis (page 4, lines 18-20). In particular, the invention of Rescigno is a composition comprising a fermented product of Lactobacillus casei or paracasei species comprising DNA sequences essentially identical to SEQ ID No 1 to 5 sequences, proper diluents and/or excipients (page 5, lines 10-13). In a preferred embodiment, the Lactobacillus species is Lactobacillus paracasei, and more preferably the strain is deposited under CNCM I-5220 (page 5, lines 15-18). Therefore, Rescigno discloses a composition comprising a postbiotic, which is a fermented product of a Lactobacillus paracasei species or mixtures thereof (in particular, postbiotic from L. paracasei CNCM I-5220), meeting a limitation of instant claim 1.
As pointed out above, the composition of Rescigno is an eyedrop formulation. See also page 5, lines 25-26. Since the composition is an eyedrop formulation, then it is directed to an ‘eye topical composition,’ meeting a limitation of instant claim 1.
In sum, Rescigno meets limitations of the claimed invention by disclosing an eye topical composition comprising a postbiotic, which is a fermented product of a Lactobacillus paracasei species or mixtures thereof (in particular, a fermented product of L. paracasei CNCM I-5220). Since Rescigno teaches the preferred embodiment of Lactobacillus paracasei CNCM I-5220, then Rescigno meets the L. paracasei strain limitation of instant claims 2, 4, and 7.
Rescigno does not expressly disclose that the postbiotic comprises a mixture of biosurfactants, proteins, and organic acids. However, the postbiotic from L. paracasei CNCM I-5220 of Rescigno necessarily comprises a mixture of biosurfactants, proteins, and organic acids since Rescigno specifically discloses a “postbiotic” that is a fermented product of Lactobacillus paracasei CNCM I-5220 which is the narrower scope of the postbiotic of instant dependent claims 2, 4, and 7. According to MPEP 2112(I), “’[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.’” Although Rescigno does not explicitly disclose the components of the postbiotic from L. paracasei CNCM I-5220, it is a postbiotic from L. paracasei CNCM I-5220 as claimed, and thus must have the same components as claimed (a mixture of biosurfactants, proteins, and organic acids). Moreover, the prior art demonstrates that biosurfactants, proteins, and organic acids are inherently a fermented product of Lactobacillus species, including Lactobacillus paracasei. As evidenced by Hatti-Kaul, L-lactic acid is known in the art as a fermented product of L. paracasei (page 3, left column, last paragraph and right column, last paragraph). Also, as evidenced by Reid, Lactobacilli produce numerous substances such as organic acids, bacteriocins and biosurfactants that kill pathogens or inhibit their adherence to surfaces (paragraph [0007]); bacteriocins are directed to proteins. The evidence of Hatti-Kaul and Reid provide a basis for supporting the determination of the inherent characteristics of the postbiotic from L. paracasei CNCM I-5220 as taught by Rescigno.
Rescigno (as evidenced by Hatti=Kaul and Reid) differs from the claimed invention in that Rescigno does not express disclose that their eyedrop formulation is ‘stable eye topical composition’ wherein ‘stable’ is defined in the instant specification as “the composition has a mean particle dispersion (size) ≤ 200 nm, in particular with reference to the postbiotic, at 40ºC and 25ºC at six months” (page 5, lines 15-17), and that, in addition to the postbiotic, the eyedrop formulation further comprises:
a water-based liquid carrier,
a buffer system comprising sodium hydrogen phosphate monohydrate and disodium phosphate dodecahydrate in amounts to yield a pH from 6.7 to 6.9, and
an isotonising agent comprising magnesium chloride hexahydrate and calcium chloride dihydrate.
Chapin discloses ophthalmic formulations useful for the treatment of ocular disorders, such as for example dry eye disease, and more particularly to ophthalmic formulations comprising a tear substitute, or one or more components thereof (paragraph [0002]). The invention provides ophthalmic formulations/compositions that are useful as a moisturizing and lubricating eye drop (i.e., an artificial tear solution) and/or a delivery vehicle for ophthalmic drugs (paragraph [0006]). In particular, Chapin discloses aqueous ophthalmic solutions containing (a) a viscosity enhancing agent or combinations of viscosity enhancing agents; (b) a tonicity agent or combination of tonicity agents; and (c) a buffer or combination of buffers, in addition to a drug for treating an eye disorder if used for that purpose (paragraph [0037]). Examples of the tonicity agents include calcium chloride and magnesium chloride (paragraphs [0043] and [0044]). In some embodiments, the tonicity component comprises four or more of sodium chloride, potassium chloride, zinc chloride, calcium chloride, and magnesium chloride; and in some embodiments, the tonicity component comprises all five of these tonicity agents (paragraph [0044]). Therefore, Chapin discloses an ophthalmic formulation (e.g., eye drops) comprising magnesium chloride and calcium chloride. Regarding the buffer or combination of buffers, preferred buffers include phosphate buffers (paragraph [0048]). A phosphate buffer system for inclusion in the invention preferably includes one or more monobasic phosphates, dibasic phosphates and the like (paragraph [0049]). Examples of suitable phosphate buffers include one or more of sodium dibasic phosphate (Na2HPO4), amongst others (paragraph [0049]). In the discussion regarding the buffers, Chapin further states that according to some embodiments, the pH of the aqueous ophthalmic solution is at or near physiological pH (paragraph [0054]). Preferably, the pH of the aqueous ophthalmic solution is between about 6.8 to about 7.7. That pH range overlaps with the pH range of ‘from 6.7 to 6.9’ of instant claim 1. Therefore, Chapin discloses a buffer system in their ophthalmic formulation (e.g., eye drops) comprising buffers including sodium dibasic phosphate to yield a pH that renders obvious the claimed pH. Additionally, Chapin states that any of a variety of carriers may be used in their formulations, including water (paragraph [0067]). Therefore, the ophthalmic formulation of Chapin comprises a water-based liquid carrier.
Gelsomino discloses an ophthalmic pharmaceutical composition for use in the treatment of the dry eye syndrome (abstract). Preferably, the compositions according to the Gelsomino invention are prepared in the form of eye drops (page 9, lines 11-12). The ophthalmic pharmaceutical composition has a pH comprised between 5.5 and 7.5 (page 8, lines 7-8), and can further contain at least one component selected from a group comprising buffering agents, osmolarity regulators, and mixtures thereof (page 8, lines 15-17). Examples of buffering agents include sodium phosphate and mixtures of the buffering agents (page 8, lines 22-26). In Example 1, an eye drop formulation is prepared by mixing hydrocortisone sodium phosphate and sodium hyaluronate with other conventional ingredients according to a method known to a person skilled in the art (page 9, line 25 through page 10, line 1). The conventional ingredients include magnesium chloride hexahydrate, Na2HPO4 dodecahydrate (i.e. disodium phosphate dodecahydrate), and Na2HPO4 monohydrate (i.e. sodium hydrogen phosphate monohydrate) (Table 1 on page 10). Purified water is also included to balance to 100 mL (Table 1 on page 10).
Gao reviewed the chemicals in branded and generic preservative-free artificial tears on the market (page 200, paragraph bridging left and right columns). The ingredients of these products are set forth in Table 1. The ingredient J is calcium chloride or calcium chloride dihydrate, and the ingredient K is magnesium chloride or magnesium chloride hexahydrate. Table 2 shows that of the 14 artificial tear products tested, 6 products had the combination of calcium chloride/calcium chloride dihydrate and magnesium chloride/magnesium chloride hexahydrate.
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to apply the teachings of Chapin, Gelsomino, and Gao regarding eyedrop (i.e. artificial tear solution) formulations to the eyedrop formulation of Rescigno (as evidenced by Hatti-Kaul and Reid), as it would have been within the scope of the skilled artisan of combining prior art elements according to known methods to yield the predictable result of obtaining eyedrop formulations suitable for application to eyes. In particular, it would have been obvious to the person of ordinary skill in the art to include a combination of tonicity agents which are calcium chloride dihydrate and magnesium chloride hexahydrate (calcium chloride and magnesium chloride taught in Chapin, calcium chloride dihydrate and magnesium chloride hexahydrate taught in Gao), a buffer system comprising sodium hydrogen phosphate monohydrate and disodium phosphate dodecahydrate (sodium dibasic phosphates taught in Gelsomino) in amounts to yield a pH between about 6.8 to about 7.7 (as taught in Chapin, rendering obvious the claimed pH) or between 5.5 and 7.5 (as taught in Gelsomino, rendering obvious the claimed pH), and water as the diluents and/or excipients sought by Rescigno for inclusion in their composition (page 5, lines 10-13). It would have been an obvious matter of substituting known ingredients (diluents and/or excipients) recognized for eyedrop formulations. Chapin serves as an overview of the contents for ophthalmic formulations, including eye drops (i.e., an artificial tear solution); Gelsomino provides specifics regarding a conventional combination of sodium dibasic phosphates, specifically the combination of sodium hydrogen phosphate monohydrate and disodium phosphate dodecahydrate, in ophthalmic pharmaceutical compositions that include eye drops; and Gao provides further specifics regarding the combination of calcium chloride and magnesium chloride which are tonicity agents taught in Chapin, disclosing calcium chloride dihydrate and magnesium chloride hexahydrate as forms that are common in artificial tear products. There would have been a reasonable expectation of success of obtaining the eyedrop formulation sought by Rescigno for protecting the eye mucosa from infections and allergic reactions and subsequent conjunctivitis because Chapin discloses that ophthalmic formulations comprising tonicity agents and buffer combinations can be used to treat eye disorders if it contains a drug for that disorder; the postbiotic of Rescigno is the active agent to obtaining their sought therapeutic effects.
Therefore, Resigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid) renders obvious an eye topical composition comprising the components of instant claim 1.
Regarding the claimed limitation of a “stable” eye topical composition, the term ‘stable’ is defined in the instant specification as “the composition has a mean particle dispersion (size) ≤ 200 nm, in particular with reference to the postbiotic, at 40ºC and 25ºC at six months” (page 5, lines 15-17). This is directed to a property of the claimed composition. According to MPEP 2112(I), “‘[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.’” Moreover, MPEP 2112(I) also states, “Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable.” Since Resigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid) renders obvious a composition comprising the same components, including the claimed ‘postbiotic,’ then the composition rendered obvious by the references is necessarily ‘stable’ as defined in the instant specification.
Therefore, Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid) renders obvious instant claims 1 and 2.
Regarding instant claim 3, as discussed above, Chapin discloses that in some embodiments, the tonicity component comprises four or more of sodium chloride, potassium chloride, zinc chloride, calcium chloride, and magnesium chloride; and in some embodiments, the tonicity component comprises all five of these tonicity agents (paragraph [0044]). In applying the teachings regarding eyedrop formulations of Chapin to the invention of Rescigno as set forth above, it further would have been obvious to incorporate the teaching of further including sodium chloride and potassium chloride with the calcium chloride hexahydrate and magnesium chloride hexahydrate of the composition rendered obvious by Rescigno, Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid). It would have been obvious to do so since they are known ingredients recognized for combination with calcium chloride and magnesium chloride as tonicity agents in eyedrop formulations. Thus, instant claim 3 is rendered obvious.
Regarding instant claim 4, Rescigno discloses that preferably, their composition comprises the fermented product at 2-40% volume (page 5, lines 27-28). This suggests a composition comprising 2-40% (w/v) postbiotic from L. paracasei CNCM no. I-5220, which overlaps with the claimed range of 0.1-5% (w/v), thereby rendering obvious the claimed limitation.
As discussed above, Chapin discloses aqueous ophthalmic solutions (e.g., eye drops as in paragraph [0006]) containing (a) a viscosity enhancing agent or combinations of viscosity enhancing agents; (b) a tonicity agent or combination of tonicity agents; and (c) a buffer or combination of buffers, in addition to a drug for treating an eye disorder if used for that purpose (paragraph [0037]). Table 5 in paragraph [0128] of Chapin summarizes possible excipients in an artificial tear solution. In that solution, the phosphate buffer is in a concentration of 0-0.5%. See also paragraph [0049] which discloses that the phosphate buffer components frequently are used in amounts from 0.01% to 0.5% (w/v). Based on these teachings, in the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it would have been obvious to the person of ordinary skill in the art to include the sodium hydrogen phosphate monohydrate and the disodium phosphate dodecahydrate in amounts that total to the concentrations taught by Chapin, as those concentrations are suitable for eyedrop formulations. Given the range of from 0.01% to 0.5% (w/v) phosphate buffer components disclosed in Chapin, then the concentrations of sodium hydrogen phosphate monohydrate and disodium phosphate dodecahydrate of instant claim 4 are rendered obvious.
Additionally, Chapin discloses in Table 5 in paragraph [0128] that the magnesium chloride is at 0-0.80%. Also, Chapin discloses that in some embodiments, magnesium chloride ranges from about 0.0005 to about 0.1% w/v, preferably about 0.005 to about 0.08% w/v (paragraph [0045]). In the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it would have been obvious to the person of ordinary skill in the art to include the magnesium chloride hexahydrate in the concentrations taught in Chapin for magnesium chloride, as those concentrations are suitable for eyedrop formulations. Since these ranges overlap with the claimed concentration range of magnesium chloride hexahydrate, then the concentration of magnesium chloride hexahydrate of instant claim 4 is rendered obvious.
Also, Chapin discloses in Table 5 in paragraph [0128] that the calcium chloride is in an amount of 0-0.80%. Chapin also discloses that in some embodiments, calcium chloride ranges from about 0.0005 to about 0.1% w/v, preferably about 0.0005 to about 0.08% w/v (paragraph [0045]). In the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it would have been obvious to the person of ordinary skill in the art to include the calcium chloride dihydrate in the concentrations taught in Chapin for calcium chloride, as those concentrations are suitable for eyedrop formulations. Since these ranges overlap with the claimed concentration range of calcium chloride dihydrate, then the concentration of calcium chloride dihydrate of instant claim 4 is rendered obvious.
Furthermore, in Table 5 in paragraph [0128], Chapin discloses inclusion of sterile water for injection as the solution base, with the concentration being q.s. without referring to the amount of water. However, Gelsomino discloses that for a preparation of an eye drop formulation, purified water is included to balance to 100 mL (page 10, lines 1-3 and Table 1). For the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it would have been obvious to the person of ordinary skill in the art to include purified water as the carrier to balance to 100 mL since it is recognized in the art (in particular, Gelsomino) for preparation of an eye drop formulation.
In sum, then instant claim 4 is rendered obvious.
Regarding instant claim 5, Chapin discloses that tonicity adjusting agents include ionic tonicity agents (e.g., calcium chloride) and/or non-ionic tonicity agents such as glycerol (paragraph [0043]). In applying the teachings regarding eyedrop formulations of Chapin to the invention of Rescigno as set forth above, it further would have been obvious to incorporate the teaching of including glycerol as a non-ionic tonicity agent in the composition rendered obvious by Rescigno, Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid). It would have been obvious to do so because glycerol is a known tonicity agent recognized for inclusion in eyedrop formulations. By including glycerol, then the composition rendered obvious by the references further includes a ‘glycerol based suspending-isotonising agent.’ Thus, instant claim 5 is rendered obvious.
Regarding instant claim 6, Chapin discloses that preferred buffers in their ophthalmic formulations/compositions include phosphate buffers, citrate buffers, and combinations and mixtures thereof (paragraph [0048]). The citrate buffer system may be comprised of sodium citrate (paragraph [0048]). In applying the teachings regarding eyedrop formulations of Chapin to the invention of Rescigno as set forth above, it further would have been obvious to incorporate the teaching of including sodium citrate as buffer for combination with the phosphate buffers in the composition rendered obvious by Rescigno, Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid). It would have been obvious to do so because sodium citrate is a known buffer recognized for combination with phosphate buffers and inclusion in eyedrop formulations. Thus, instant claim 6 is rendered obvious.
Regarding instant claim 7, Rescigno discloses that preferably, their composition comprises the fermented product as 2-40% volume (page 5, lines 27-28). This suggests a composition comprising 2-40% (w/v) postbiotic from L. paracasei CNCM no. I-5220, which is above the claimed concentration of 0.28% (w/v). However, it would have been an obvious matter of routine optimization to vary the concentration of the postbiotic of the composition rendered obvious by Rescigno, Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid) since the skilled artisan would have recognized that the concentration of the postbiotic would have affected its efficacy in protecting the eye mucosa from infections and allergic reactions and subsequent conjunctivitis. The postbiotic is the therapeutic agent of the composition rendered obvious by the references. As pointed out by Chapin, the amount of an ophthalmic drug included in their ophthalmic compositions (e.g., eye drops) will be whatever amount is therapeutically effective and will depend upon a number of factors, including the identity and potency of the chosen drug (paragraph [0061]). Also, Chapin teaches that the dosage of any ophthalmic drug may also vary depending on the symptoms, age and other physical characteristics of the patient, the nature and severity of the disorder to be treated or prevented, etc. (paragraph [0062]). These teachings of Chapin support routine optimization of the concentration of the postbiotic of the composition rendered obvious by Rescigno, Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), including to a concentration of 0.28% (w/v). It is noted that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, the references render obvious the claimed postbiotic concentration.
As discussed above, Chapin discloses aqueous ophthalmic solutions (e.g., eye drops as in paragraph [0006]) containing (a) a viscosity enhancing agent or combinations of viscosity enhancing agents; (b) a tonicity agent or combination of tonicity agents; and (c) a buffer or combination of buffers, in addition to a drug for treating an eye disorder if used for that purpose (paragraph [0037]). Table 5 in paragraph [0128] of Chapin summarizes possible excipients in an artificial tear solution. In that solution, the phosphate buffer is in a concentration of 0-0.5%. See also paragraph [0049] which discloses that the phosphate buffer components frequently are used in amounts from 0.01% to 0.5% (w/v). Based on these teachings, in the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it would have been obvious to the person of ordinary skill in the art to include the sodium hydrogen phosphate monohydrate and the disodium phosphate dodecahydrate in amounts that total to the concentrations taught by Chapin, as those concentrations are suitable for eyedrop formulations. Moreover, it would have been an obvious matter of routine optimization to vary the concentrations of the sodium hydrogen phosphate monohydrate and the disodium phosphate dodecahydrate of the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid) to 0.1600% (w/v) and 0.4100% (w/v), respectively, since the skilled artisan would have recognized that the concentrations of these two buffers can be varied to yield desired levels of buffering. It is noted that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Therefore, the references render obvious the claimed sodium hydrogen phosphate monohydrate and disodium phosphate dodecahydrate concentrations.
As discussed above with respect to instant claim 6, it would have been obvious to further include sodium citrate in the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), based on the teachings of Chapin. Chapin discloses in Table 5 in paragraph [0128] that the citrate buffer is in an amount of 0-0.5%. It would have been obvious to include the sodium citrate in an amount falling within the range of 0-0.5% (w/v) in the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), since Chapin discloses that concentration as suitable for an artificial tear formulation (i.e., eye drops). Since that concentration range includes the claimed sodium citrate concentration of 0.0590% (w/v), then the claimed sodium citrate concentration is rendered obvious.
As discussed above with respect to instant claim 3, it would have been obvious to further include sodium chloride and potassium chloride in the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), based on the teachings of Chapin. Chapin discloses that in some embodiments, sodium chloride ranges from about 0.1 to about 1% w/v, preferably from about 0.2 to about 0.8% w/v, and more preferably about 0.39% w/v (paragraph [0045]). Each of the two ranges include the claimed sodium chloride concentration, and the concentration of about 0.39% w/v is close to the claimed sodium chloride concentration. It would have been obvious to include the sodium chloride in an amount falling within the ranges of from about 0.1 to about 1% w/v, and from about 0.2 to about 0.8% w/v, in the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), since Chapin discloses those concentrations as suitable for an eye drop formulation. Since those concentration ranges include the claimed sodium chloride concentration of 0.3500% (w/v), then the claimed sodium chloride concentration is rendered obvious. Further still, Chapin discloses that in some embodiments, potassium chloride ranges from about 0.02 to about 0.5% w/v, preferably about 0.05 to about 0.3% w/v, and more preferably about 0.14% w/v (paragraph [0045]). Each of the two ranges include the claimed potassium chloride concentration, and the concentration of about 0.14% w/v is close to the claimed potassium chloride concentration of 0.1500% (w/v). It would have been obvious to include the potassium chloride in an amount falling within the ranges of from about 0.02 to about 0.5% w/v or from about 0.05 to about 0.3% w/v, or in an amount of about 0.14% w/v, in the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), since Chapin discloses those concentrations as suitable for an eye drop formulation. Since those concentration ranges include the claimed potassium chloride concentration and the concentration of about 0.14% w/v is merely close to the claimed potassium chloride concentration (see MPEP 2114.05(I)), then the claimed potassium chloride concentration is rendered obvious.
Additionally, Chapin discloses in Table 5 in paragraph [0128] that the magnesium chloride is at 0-0.80%. Also, Chapin discloses that in some embodiments, magnesium chloride ranges from about 0.0005 to about 0.1% w/v, preferably about 0.005 to about 0.08% w/v (paragraph [0045]). In the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it would have been obvious to the person of ordinary skill in the art to include the magnesium chloride hexahydrate in the concentrations taught in Chapin for magnesium chloride. Since these ranges include the claimed concentration of magnesium chloride hexahydrate, then the concentration of magnesium chloride hexahydrate of instant claim 7 is rendered obvious.
Also, Chapin discloses in Table 5 in paragraph [0128] that the calcium chloride is in an amount of 0-0.80%. Chapin also discloses that in some embodiments, calcium chloride ranges from about 0.0005 to about 0.1% w/v, preferably about 0.0005 to about 0.08% w/v (paragraph [0045]). In the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it would have been obvious to the person of ordinary skill in the art to include the calcium chloride dihydrate in the concentrations taught in Chapin for calcium chloride. Since these ranges include the claimed concentration of calcium chloride dihydrate, then the concentration of calcium chloride dihydrate of instant claim 7 is rendered obvious.
As discussed above with respect to instant claim 5, it would have been obvious to further include glycerol in the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), based on the teachings of Chapin. Glycerol is disclosed as a viscosity enhancing agent in Chapin for inclusion in aqueous ophthalmic solutions (e.g., eye drops) (paragraph [0039]). Chapin discloses that in some embodiments, the concentration of the viscosity enhancing agent ranges from about 0.2% to about 10% w/v (paragraph [0039]). In the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it would have been obvious to the person of ordinary skill in the art to include the glycerol in the concentrations taught in Chapin for viscosity enhancing agents such as glycerol, as those concentrations are suitable for eyedrop formulations. Since the viscosity enhancing agent (e.g., glycerol) range includes the claimed concentration of glycerol, then the concentration of glycerol of instant claim 7 is rendered obvious.
Furthermore, in Table 5 in paragraph [0128], Chapin discloses inclusion of sterile water for injection as the solution base, with the concentration being q.s. without referring to the amount of water. However, Gelsomino discloses that for a preparation of an eye drop formulation, purified water is included to balance to 100 mL (page 10, lines 1-3 and Table 1). For the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it would have been obvious to the person of ordinary skill in the art to include purified water as the carrier to balance to 100 mL since it is recognized in the art (in particular, Gelsomino) for preparation of an eye drop formulation.
In sum, then instant claim 7 is rendered obvious.
Regarding instant claim 8, Chapin discloses aqueous ophthalmic solutions (e.g., eye drops as in paragraph [0006]) containing (a) a viscosity enhancing agent or combinations of viscosity enhancing agents; (b) a tonicity agent or combination of tonicity agents; and (c) a buffer or combination of buffers, in addition to a drug for treating an eye disorder if used for that purpose (paragraph [0037]). Table 5 in paragraph [0128] of Chapin summarizes possible excipients in an artificial tear solution. Chapin discloses in Table 5 in paragraph [0128] that the magnesium chloride is at 0-0.80%. Also, Chapin discloses that in some embodiments, magnesium chloride ranges from about 0.0005 to about 0.1% w/v, preferably about 0.005 to about 0.08% w/v (paragraph [0045]). In the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it would have been obvious to the person of ordinary skill in the art to include the magnesium chloride hexahydrate in the concentrations taught in Chapin for magnesium chloride.
Also, Chapin discloses in Table 5 in paragraph [0128] that the calcium chloride is in an amount of 0-0.80%. Chapin also discloses that in some embodiments, calcium chloride ranges from about 0.0005 to about 0.1% w/v, preferably about 0.0005 to about 0.08% w/v (paragraph [0045]). In the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it would have been obvious to the person of ordinary skill in the art to include the calcium chloride dihydrate in the concentrations taught in Chapin for calcium chloride.
Based on the concentration ranges of the magnesium chloride hexahydrate and the calcium chloride dihydrate of the composition rendered obvious by Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid), it follows that the magnesium chloride hexahydrate to calcium chloride dihydrate weight ratio of instant claim 8 is rendered obvious. For instance, the calcium chloride dihydrate range includes 0.0005% w/v, and the magnesium chloride hexahydrate range includes 0.00071% w/v. In that case, the weight ratio of the magnesium chloride hexahydrate to the calcium chloride dihydrate is 1.42 (i.e. 10/7) [Calculation: 0.00071% w/v/0.0005% w/v = 1.42].
Regarding instant claim 9, Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid) differs from the claimed invention in that they do not expressly disclose a composition having a particle average dispersion size ≤ 200 nm at 40ºC after six months (Note: the claimed limitation ‘after six months’ is different from the disclosure of “at six months” for the definition of the limitation ‘stable’ in the instant specification on page 5, lines 15-17). According to MPEP 2112(I), “’[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.’” Moreover, MPEP 2112(I) also states, “Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable.” Since Rescigno in view of Chapin, Gelsomino, and Gao (as evidenced by Hatti-Kaul and Reid) renders obvious an eye topical composition comprising the same components, including the claimed ‘postbiotic,’ then it necessarily possesses the claimed characteristic of having a particle average dispersion size ≤ 200 nm at 40ºC after six months. Therefore, instant claim 9 is rendered obvious.
Response to Arguments
Applicant’s arguments, filed May 14, 2026, with respect to the rejection under 35 U.S.C. 103 of claims 1, 3, 5, 6, 8, and 9 as being unpatentable over Hecht in view of Gelsomino, and in light of Hatti-Kaul; the rejection under 35 U.S.C. 103 of claim 2 as being unpatentable over Hecht, Gelsomino, and Hatti-Kaul in further view of Rescigno; and the rejection under 35 U.S.C. 103 of claims 2, 4, and 7 as being unpatentable over Hecht, Gelsomino, and Hatti-Kaul in further view of Rescigno and Naserke, have been fully considered and are persuasive. In particular, the rejections have been overcome by the amendment to claim 1 since Hecht does not disclose a postbiotic comprising a mixture of biosurfactants, proteins, and organic acids. Therefore, these rejections have been withdrawn.
However, upon further consideration, a new ground(s) of rejection is made in view of Rescigno (previously cited as a secondary reference) as a primary reference, in combination with Chapin (newly cited), Gelsomino (previously cited), and Gao (newly cited), as evidenced by Hatti-Kaul (previously cited) and Reid (newly cited), as necessitated by the amendments to the claims.
To the extent Applicant’s arguments and evidence (Exhibits A and B) are directed to the new grounds of rejection, they are unpersuasive. Applicant cites Example 2, in particular paragraphs [0069]-[0074] of the published application and Figure 5B, for demonstrating that formulations lacking the claimed buffer system, even those containing the same postbiotic and isotonising agents, fails to maintain stability, forming visible precipitates within one week at 40ºC. The formulation tested in Example 2 for obtaining Figure 5B comprises the postbiotic, sodium chloride, and purified water (paragraph [0073] of published application), with Figure 5B showing photographic reproduction of the formulation containing postbiotic obtained from the fermentation of Lactobacillus paracasei CNCM I-5220 in water and NaCl, kept for one week at 40º. However, the specification does not include for comparison photographic reproduction of the formulation containing the postbiotic, the buffer system of at least claim 1, and the isotonising agent of at least claim 1, nor has Applicant provided such evidence. Since there is no such photographic reproduction for comparison with Figure 5B, then it cannot be ascertained that the formulation according to the instant claims is “stable” and does not form visible precipitates within one week at 40ºC. Paragraph [0074] of the published application states that other tests were performed on buffers with a pH value equal to 5.6-5.8 (formulations 3 and 4), but without satisfactory results at lower concentrations of postbiotic (0.1%), the average particle dispersion (size) values obtained are in both cases greater than 200 nm. However, the formulation used in Example 2 is a postbiotic from L. paracasei CNCM I-5220 which is not commensurate in scope with claims 1, 3, 5, 6, 8, and 9 which have a broader scope of a postbiotic from a Lactobacillus paracasei species; and claims 1-6, 8, and 9. Even with respect to claims 4 and 7, it is unclear from the evidence of Example 2 that the specific claimed combinations of components and their concentrations are critical for the formulation stability and particle, given that paragraph [0074] of the published application, which tested formulation 3 and 4, refers to the lower concentration of postbiotic of 0.1% in the tested formulations which falls in the scope of claim 4, and different combinations of components are present in formulations 3 and 4 that make it unclear that the formulations of claims 4 and 7 would arrive at an unexpected particle size, as opposed to the presence/absence/concentration of individual components. Compared to claim 4, formulation 3 does not comprise magnesium chloride hexahydrate and calcium chloride dihydrate, but comprises sodium chloride, so it is unclear whether their test results are due to the absence of the two buffers and/or the presence of sodium chloride. When compared to claim 7, formulation 3 does not comprise the claimed two buffers, but also does not comprise sodium citrate, potassium chloride, and glycerol, so it is unclear whether their test results are due to the absence of the two buffers and/or the absence of any one or any combination of sodium citrate, potassium chloride, and glycerol. Compared to claim 4, formulation 4 does not comprise sodium hydrogen phosphate monohydrate, magnesium chloride hexahydrate, and calcium chloride dihydrate, but comprises citric acid, so it is unclear whether their test results are due to the absence of sodium hydrogen phosphate monohydrate, magnesium chloride hexahydrate, and/or calcium chloride dihydrate, and/or the presence of citric acid. Compared to claim 7, formulation 4 does not comprise sodium hydrogen phosphate monohydrate, sodium chloride, potassium chloride, magnesium chloride hexahydrate, calcium chloride dihydrate, and glycerol, so it is unclear whether their test results are due to the absence of any one or any combination of those components.
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 (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SUSAN E. FERNANDEZ/ Examiner, Art Unit 1651
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