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 .
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.
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.
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, 3-5, 7-8, 10, 17-20, 23-25, 28-29, 31-44, and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Lindley (EP Publication No. 0028905 B1) in view of von Maltzahn (US 2017/0151269 A1, previously presented), as evidenced by Culturelle (“Culturelle Digestive Daily Probiotic Capsules”) in view of WO 2020252545.
Lindley’s general disclosure relates to compressed tablets containing isomaltulose and the use thereof (see Lindley at Title; at pg. 2).
Regarding claim 1, Lindley teaches a compressed tablet/lozenge or product comprising isomaltulose and teaches the use of isomaltulose as a desirable and suitable diluent in such products (see Lindley at pg. 3, lines 1-13). Particularly, Lindley teaches that isomaltulose is “especially suitable for use as a diluent material in tablets… [has] better solubility in water than lactose, does not demand careful, controlled granulation, and can be formed into tablets by direct compression with a lubricant…has a pleasant, not very sweet, reasonably bland taste and can allow other ingredients to exert a flavoring agent…can contribute bulk, body, mouthfeel and other desired characteristics to tablets for human and animal consumption” (see Lindley at pg. 3, lines 5-13).
Lindley specifically teaches “Exceptionally, isomaltulose can give coherent tablets by direct compression with a lubricant, thereby avoiding the need for a binder. Isomaltulose can be used as diluent for various physiologically active ingredients. [0019]. Lindley teaches moist granulation (also known as wet granulation) involving wetting of the ingredients to give a moist, coherent powder, then sieving, and controlled drying to give granules suitable for preparation of tabletting powders.[0004] The reference teaches that isomaltulose does not require this process and can be directly compressed. Lindley teaches the ingredients are mixed and compressed. However, Lindley teaches the formulations can be prepared using any technique in the art to ensure proper granulation and intimate and thorough mixing of the ingredients. [0023]. The examples use both wet granulation and direct compression.
Regarding claim 5, 23, 28 Lindley teaches peppermint flavor (reads on aromatizing agent), sweeteners, and magnesium stearate.
Regarding claims 7 and 31-32, Lindley teaches that the tablet or lozenge can comprise up to 97% isomaltulose, ranging typically from 10-95%, and can comprise from 3-90% of the active ingredient (see Lindley at page 4 at lines 4-10). Further, Lindley teaches that the tables typically weigh from 5 mg to 5 g (see Lindley at page 4, lines 12-13). It is noted that where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (See MPEP 2144.05 I). It is noted that “where 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” (See MPEP 2144.05 II).
Additionally, regarding claim 8 and 36-38, Lindley teaches the dissolution of the compressed tablets and notes that isomaltulose-based tablets were faster to dissolve than lactose-based tablets, particularly at lower temperatures (see Lindley at pg. 4, lines 60-65). To reiterate, it is within the skill of an artisan to manipulate the amount of disintegrants to yield the desired disintegration time.
The primary reference differs from the instant claims as follows: Although Lindley teaches isomaltulose-based tablets, Lindley does not teach tablets containing probiotics as required by instant claim 1. Further Lindley does not teach the amended limitation of compression force of 6 to10kN as required by instant claim 1.
von Maltzahn’s general disclosure relates to the preparation of glycan therapeutics, pharmaceutical compositions, and medical foods, comprising micronutrients, polyphenols, prebiotics, probiotics and other agents (see Abstract).
Regarding claim 1, von Maltzahn teaches a composition comprising a probiotic (see von Maltzahn at ¶[0268]; at ¶[0286]-[0288]). Additionally, von Maltzahn teaches the composition can be compressed (see von Maltzahn at ¶[0302]) and in the form of a lozenge (see von Maltzahn at ¶[0315]).
Regarding claim 3, von Maltzahn teaches the composition can comprise lactic acid bacteria (see von Maltzahn at ¶[0286]-[0288]).
Regarding claim 4, von Maltzahn teaches the composition can comprise one or more excipients or carriers (see von Maltzahn at ¶[0268]).
Regarding claim 24, 28, 43, von Maltzahn teaches the composition can further comprise lubricants (see von Maltzahn at ¶[0268]), active ingredient (see von Maltzahn at ¶[0302]), and sweeteners (see von Maltzahn at ¶[0317]); silicon dioxide; HPMC [317]
Regarding claim 8 and 36-38, von Maltzahn teaches the product contains disintegrants to facilitate tablet disintegration after administration and provides examples thereof (see von Maltzahn at ¶[0372]). It is within the skill of artisan to manipulate the amount of disintegrants to yield the desired disintegration time. A skilled artisan could readily modify a known compound, a disintegrant, in a tablet or lozenge in a known and predictable manner to routine optimize the disintegration time, wherein disintegration time can be predictably increased or decreased by altering the amount of disintegrant present in the tablet or lozenge (see MPEP 2144.05 (II)). Further, the composition as claimed is similar to the prior art’s composition, probiotic and isomaltulose, thus the properties would be the same absent evidence otherwise.
Regarding claim 10, von Maltzahn teaches that the product may be contained in a package (see von Maltzahn at ¶[0372]).
Regarding claims 1, 17-18, 39, 42, and 44, instant claims product-by-process limitations. Per MPEP 2113(I), patentability is based on the product itself (structure) rather than the method of production. Here, the process limitations presently recited are not related to a structure and therefore are presumably met by the prior art, absent evidence to the contrary. Applicant has not provided any evidence that the process including the compression force provides a different structure and therefore, it is the position of the examiner the combination of references would produce the same product.
Regarding claim 19, von Maltzahn teaches suitable probiotic microorganisms includes those from the genus of Bifidobacterium, Lactobacillus, Enterococcus, and Streptococcus (see von Maltzahn at ¶[0286]).
Regarding claim 20, von Maltzahn teaches L. crispatus, L. casei, L. rhamnosus,
L. fermentum, L. plantarum, L. reuteri, S. salivarius and B. animalis (see von Maltzahn at ¶[0286] & [0288]).
Regarding claim 23 and 40, von Maltzahn teaches one or more excipients or carriers including diluents, binders, disintegrants, dispersants, lubricants, glidants, stabilizers, surfactants, flavoring agents, and colorants (see von Maltzahn at ¶[0268]).
Regarding claim 24, 28, 41, and 43, von Maltzahn teaches that lubricant comprises magnesium stearate, a glidant or anti-caking agent comprises silicon dioxide, and binders comprise hydroxylpropylcellulose and natural substitutes such as corn starch and pregelatinized starch, and teaches a flavoring agent, natural sweeteners, and one or more active ingredients (see von Maltzahn at ¶[0317]; at ¶[0302]).
Regarding claim 25 and 29, von Maltzahn teaches the flavoring agent may be mint, cherry, anise, peach, apricot, licorice, raspberry, vanilla, and the like (see von Maltzahn at ¶[0317]) and teaches a polyphenol extracted from the juice of a strawberry (see von Maltzahn at ¶[0352]). Additionally, von Maltzahn teaches the sweetener can comprise W (see von Maltzahn at ¶[0317]). It is within the skill level of one of ordinary skill in the art to choose a flavor, such as strawberry, given the teachings above.
von Maltzahn teaches that the composition can comprise vitamins and minerals as dietary ingredients or active ingredients (see von Maltzahn at ¶[0299]).
von Maltzahn teaches the composition can comprise vitamin D (see von Maltzahn at ¶[0274]). It is within the skill level of an ordinary artisan with the teachings of von Maltzahn to use vitamin D3 in the composition.
Regarding claims 33-35, von Maltzahn teaches that the composition contains probiotic bacterial strains in an amount compressed from 1x107-1x1013 CFU/dose (see von Maltzahn at ¶[0540]). As evidence by Culturelle, a dose of 10 billion CFUs or 1x1010 CFUs of Lactobacillus rhamnosus GG is equal to about 40 mg. von Maltzahn discloses a dosage amount from 5 mg/kg to 500 mg/kg, which would convert to a concentration from 8-100% (see von Maltzahn at ¶[0537]). It is within the skill of an ordinary artisan to use the teachings of von Maltzahn to arrive at a concentration or amount in mg as claimed. It is reiterated that where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (See MPEP 2144.05 I). It is reiterated that “where 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” (See MPEP 2144.05 II).
In the interest of compact prosecution WO ‘545 is cited their teaching of the state of the art and the use of the instantly claimed compression force and WO ‘168 is optionally cited for wet granulation.
WO ‘545 teaches a tablet containing the probiotics Lactobacillus acidophilus and Bifidobacterium lactis. All of these steps are carried out in a controlled environment, that is, with temperature and humidity strictly monitored. The temperature of the production rooms is a maximum of 25 ° C and the humidity is up to 50% U.R [0028]
WO teaches “A first goal to achieve is to have an adequate number of UFCs (colony-forming unit) per day…. The bacterial strains of the present invention are strains producing lactic acid and / or probiotics, and are of the species Lactobacillus acidophilus and Bifidobacterium lactis and are in the 10 .sup.9 UFC range.” [0027].
WO teaches, “Compression of probiotics is a process that requires special care. The force required to generate tablets must be finely controlled so that it does not cause significant impacts on the viability of the strains present in the formulation. The greater the force applied to obtain the tablets, the greater the loss of probiotics during the manufacturing process and over the product's shelf life.” WO teaches the use of 8kn and 10 compression force. WO ‘545 teaches the excipient and its ability to take the impact of the punches is important [0031] “Physical aspects such as humidity and water activity are decisive when choosing the matrix used….so that there is no activation of probiotic microorganisms in the tablet and, thus, accelerate the degradation of the product, decreasing the potency and activity of the microorganisms. The excipients compatible with the probiotics must have other characteristics besides low water activity and controlled humidity, they must also be compressible with a low compression force, since the impact of the compression directly interferes in the viability of the probiotic strains.” [0033]. [0034] teaches the preservation of the probiotics for 24 months (reads on instant claim 47). Silicon dioxide and talc taught. [0032]
Therefore, first, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reasons:
The ordinary artisan would be motivated to use isomaltose as an excipient in a compressed lozenge probiotic composition. An ordinary artisan would expect the combination of isomaltulose as an excipient or a desirable and suitable diluent and probiotic microorganisms as an active ingredient to provide predictable results and would readily improve a known probiotic compressed lozenge. A conclusion of obviousness can be made when: combining prior art elements according to known methods yields predictable results, use of known technique improves similar devices (methods, or products) in the same way, and some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings arrives at the claimed invention (see MPEP 2143 (I)(A),(C),(G)). Further, the selection of a known material based on its suitability for its intended use supports a prima facie obviousness determination (see MPEP 2144.07).
In this case, an ordinary artisan would recognize from the teachings of Lindley and von Maltzahn that isomaltulose as an excipient or diluent in composition can be predictably and desirably combined with a probiotic microorganisms to predictably form a compressed product or lozenge having the benefits described by both references; therefore, its intended use is well-known and recognized in the prior art. Further, an ordinary artisan could readily combine known probiotic microorganisms with isomaltulose for its known purpose to yield predictable results or improve a product (i.e., a probiotic lozenge product). An ordinary artisan would therefore arrive at the claimed invention by simple combination of prior art elements to arrive at a known probiotic lozenge product comprising a known excipient, isomaltulose. Moreover, regarding the product-by-process limitations, per MPEP 2113, burden shifts to applicant to show the unobvious difference with evidence once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art. The art teaches wet granulation and a compressed product.
However, in the interest of compact prosecution, the following obviousness rationale is made: It would have been obvious for one of ordinary skill in the art to combine the references and utilize the instant compression force and the process of wet granulation. Once would have been motivated to do so with reasonable expectation since WO ‘545 teaches the use of minimal force during compression such as 8k/N and 10k/N to preserve the viability of the probiotics during storage. Moreover, WO ‘545 teaches the excipient chosen to be compatible with the probiotics must have (1) low humidity and water activity so that there is no activation of probiotic microorganisms in the tablet and, thus, accelerate the degradation of the product, decreasing the potency and activity of the microorganisms and (2) must also be compressible with a low compression force, since the impact of the compression directly interferes in the viability of the probiotic strains.” As taught by Lindley, isomaltulose has the characteristics required.
Further, Lindley teaches both direct compression and wet granulation followed by compression to formulate the dosage form. Therefore, it would have been obvious to utilize wet granulation as suggested by Lindley if one wanted to ensure an intimate mixture. Thus, the state of the art establishes that it is within the skill of an artisan to formulate dosage forms using either direct compression or wet compression followed by compressions at the claimed compression force to preserve probiotic viability.
Claim 6 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Lindley (EP Publication No. 0028905 B1) in view of von Maltzahn (US 2017/0151269 A1, previously presented) as evidenced by Culturelle (“Culturelle Digestive Daily Probiotic Capsules”) in view of WO 2020252545 and further in view of Schultz (“Rice-based excipients can boost organic, non-GMO claims for supplements”, previously presented).
The teachings of von Maltzahn, Lindley, WO ‘545 have been set forth above.
However, the references do not teach the use of rice extract blend as an excipient.
Schultz’s general disclosure relates to the benefits of using rice-based excipients.
Schultz teaches that rice bran-based excipients can be used to substitute for non-organic lubrication, anti-caking, and flow agents in supplement formulations, including “a tablet or capsule”, which an artisan would readily appreciate include lozenges (see Schultz at p. 1 at para. 1-5).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reasons:
The ordinary artisan would be motivated to select rice bran-based excipients for lubrication or anti-caking (see Id.). An ordinary artisan would expect the selection or substitution for non-organic lubricant or anti-caking agents to provide predictable results and would readily improve the known probiotic product. A conclusion of obviousness can be made when: simple substitution of one known element for another obtains predictable results, use of known technique to improve similar products in the same way, and substituting equivalents known for the same purpose (see MPEP 2143 (I)(B),(C); MPEP 2144.06 (II)).
In this case, an ordinary artisan would recognize that the known rice bran-based excipients can be substituted for another lubricant or anti-caking agent (i.e., the same purpose – lubrication and anti-caking) and the use thereof is known to provide an organic alternative (i.e., an improvement to the product). The simple substitution for rice bran-based excipients would obtain predictable results and/or improve the product, since rice bran-based excipients have a well-known purpose recognized by the art.
Claims 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Lindley (EP Publication No. 0028905 B1) in view of von Maltzahn (US 2017/0151269 A1, previously presented) as evidenced by Culturelle (“Culturelle Digestive Daily Probiotic Capsules in view of WO 2020252545 and further in view of Klassen (EP Publication No. 2452575 A1).
The teachings of von Maltzahn, Lindley, WO ‘545, have been set forth above.
The references do not teach specific bacterial strains.
Klassen’s general disclosure relates to a nutritional composition having varying probiotic content (see Abstract). Klassen teaches the use of Streptococcus salivarius K12 as a probiotic microorganism in the nutritional composition (see Klassen at ¶[0028]). Klassen teaches the use of Lactobacillus rhamnosus LGG as a probiotic microorganism in the nutritional composition (see Klassen at ¶[0029]).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reasons:
The ordinary artisan would be motivated to select Streptococcus salivarius K12 and Lactobacillus rhamnosus LGG as a probiotic microorganism in the nutritional composition (see Klassen at ¶[0029]). An ordinary artisan would expect the selection to provide predictable results and would readily improve the known probiotic lozenge product. A conclusion of obviousness can be made when: combining prior art element according to known methods yield predictable results, the use of known technique improves similar devices (methods, or products) in the same way, and some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings arrives at the claimed invention (see MPEP 2143 (I)(A),(C),(G)). In this case, the known probiotic lactic acid bacteria, Streptococcus salivarius K12 and Lactobacillus rhamnosus LGG, can be used in the known the probiotic lozenge product comprising isomaltulose to yield predictable results and/or improve the product by providing beneficial health effects (see Klassen at ¶[0049]). An ordinary artisan could with the teachings provided by the prior art modify or combine prior art elements to arrive at the claimed invention.
Claims 1, 3-5, 7-8, 10, 17-19, 23-25, 28-29, 31-42, 44, and 47 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020252545, in view of Lindley (EP Publication No. 0028905 B1) optionally in view of WO 2008039531.
WO ‘545 teaches a tablet containing the probiotics Lactobacillus acidophilus and Bifidobacterium lactis and the method of preparing using compression. [0024]. The composition comprises the probiotics and an excipients. A lozenge is defined as a medicinal tablet with the intended use of dissolving in the mouth and therefore WO teaches a lozenge since WO teaches a small tablet that can dissolve in the mouth.
WO teaches “A first goal to achieve is to have an adequate number of UFCs (colony-forming unit) per day…. The bacterial strains of the present invention are strains producing lactic acid and / or probiotics, and are of the species Lactobacillus acidophilus and Bifidobacterium lactis and are in the 10 .sup.9 UFC range.” [0027] WO teaches the concentration of the probiotic in the formulation can be 5-25% of Lactobacillus acidophilus and 2.5-25% Bifidobacterium lactis [0039]. Excipients include lubricants (magnesium stearate), anti-humectants (silicon dioxide). Lactose, corn starch (reads on natural substitute binder), microcrystalline cellulose. [0032]
WO teaches, “Compression of probiotics is a process that requires special care. The force required to generate tablets must be finely controlled so that it does not cause significant impacts on the viability of the strains present in the formulation. The greater the force applied to obtain the tablets, the greater the loss of probiotics during the manufacturing process and over the product's shelf life.” WO teaches the use of 8k/N and 10k/N compression force. WO ‘545 teaches the excipient and its ability to take the impact of the punches is important [0031] “Physical aspects such as humidity and water activity are decisive when choosing the matrix used….so that there is no activation of probiotic microorganisms in the tablet and, thus, accelerate the degradation of the product, decreasing the potency and activity of the microorganisms. The excipients compatible with the probiotics must have other characteristics besides low water activity and controlled humidity, they must also be compressible with a low compression force, since the impact of the compression directly interferes in the viability of the probiotic strains.” [0033]. [0034] teaches the preservation of the probiotics for 24 months. All of these steps are carried out in a controlled environment, that is, with temperature and humidity strictly monitored. The temperature of the production rooms is a maximum of 25 ° C and the humidity is up to 50% U.R [0028]
WO teaches does not teach the instantly claimed excipient, isomaltulose or wet granulation.
Lindley teaches a compressed tablet/lozenge or product comprising isomaltulose and teaches the use of isomaltulose as a desirable and suitable diluent in such products (see Lindley at pg. 3, lines 1-13). Particularly, Lindley teaches that isomaltulose is “especially suitable for use as a diluent material in tablets… [has] better solubility in water than lactose, does not demand careful, controlled granulation, and can be formed into tablets by direct compression with a lubricant…has a pleasant, not very sweet, reasonably bland taste and can allow other ingredients to exert a flavoring agent…can contribute bulk, body, mouthfeel and other desired characteristics to tablets for human and animal consumption” (see Lindley at pg. 3, lines 5-13). Lindley specifically teaches “Exceptionally, isomaltulose can give coherent tablets by direct compression with a lubricant, thereby avoiding the need for a binder. Isomaltulose can be used as diluent for various physiologically active ingredients. [0019]
Lindley teaches that the tablet or lozenge can comprise up to 97% isomaltulose, ranging typically from 10-95%, and can comprise from 3-90% of the active ingredient (see Lindley at page 4 at lines 4-10). Further, Lindley teaches that the tablets typically weigh from 5 mg to 5 g (see Lindley at page 4, lines 12-13). It is noted that where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (See MPEP 2144.05 I). It is noted that “where 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” (See MPEP 2144.05 II).
Lindley teaches a composition that comprise a binder, peppermint (reads on aromatizing agent), magnesium stearate (reads on lubricant), starch (reads on natural substitute of HPMC), and sucrose (sweetener).
Lindley teaches moist granulation (also known as wet granulation) involving wetting of the ingredients to give a moist, coherent powder, then sieving, and controlled drying to give granules suitable for preparation of tabletting powders.[0004] The reference teaches that isomaltulose does not require this process and can be directly compressed. Lindley teaches the ingredients are mixed and compressed. Lindley also teaches the formulations can be prepared using any technique in the art to ensure proper granulation and intimate and thorough mixing of the ingredients. [0023] . The examples use both wet granulation and direct compression.
WO ‘531 teaches probiotic oral dosage forms. WO ‘531 teaches procedures for preparing tablets, caplets, and capsules are known to those of ordinary skill in the art and include without limitation wet granulation, dry granulation, and direct compression [0052]. WO’ 531 teaches the process of both and teaches with wet granulation, the powder is moistened thus creating large "chunks" of material that are subsequently dried and milled to convert the chunks to particles of a desired size for the manufacturing process. [0054] Wet granulation agents include calcium carbonate, lactose, maltodextrin, mannitol, microcrystalline cellulose, povidone, and starch. [0063].
Therefore, first, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reasons:
The ordinary artisan would be motivated to use isomaltose as an excipient in a compressed lozenge probiotic composition. An ordinary artisan would expect the combination of isomaltulose as an excipient or a desirable and suitable diluent and probiotic microorganisms as an active ingredient to provide predictable results and would readily improve a known probiotic compressed lozenge. Further, the selection of a known material based on its suitability for its intended use supports a prima facie obviousness determination (see MPEP 2144.07).
In this case, an ordinary artisan would recognize from the teachings of WO ‘545 and Lindley that isomaltulose as an excipient or diluent in composition can be predictably and desirably combined with a probiotic microorganisms to predictably form a compressed product or lozenge having the benefits described by both references; therefore, its intended use is well-known and recognized in the prior art. WO ‘545 teaches the excipient chosen to be compatible with the probiotics must have (1) low humidity and water activity so that there is no activation of probiotic microorganisms in the tablet and, thus, accelerate the degradation of the product, decreasing the potency and activity of the microorganisms” and isomaltulose has the characteristics required since Lindley teaches isomaltulose has better solubility in water than lactose and can be directly compressed or wet granulated for uniform mixture prior to compression.
Further, it would have been obvious to look to the teachings of Lindley and utilize wet granulation prior to compression. One would have been motivated to do since Lindley teaches it is within the skill of an artisan to use wet granulation to ensure adequate mixing of the excipients. One would have expected success since Lindley teaches isomaltulose may be wet granulated prior to compression or directly compressed. Thus, to utilize wet granulation rather than direct compression is known in the art. Moreover, WO ‘531 establishes it is known in the in the art to utilize wet granulation, dry granulation followed by compression, or direct compression. It is within the skill of an artisan to utilize the appropriate process to formulate a dosage form.
Regarding claim 8 and 36-38, Lindley teaches the dissolution of the compressed tablets and notes that isomaltulose-based tablets were faster to dissolve than lactose-based tablets, particularly at lower temperatures (see Lindley at pg. 4, lines 60-65). To reiterate, it is within the skill of an artisan to manipulate the amount of disintegrants to yield the desired disintegration time. Furthermore since the structure claimed is similar to the combination of WO and Lindley, probiotics and isomaltutlose, the properties should be similar absent evidence otherwise.
Regarding claims 5, 23-25, 28-29, note the 112b rejections and claim interpretation discussed above. WO teaches magnesium stearate (lubricant).
Regarding claim 10, it is within the skill of an artisan to package the tablets/lozenge for commercial sale.
Regarding 33-35, since WO ‘545 teaches be 5-25% of Lactobacillus acidophilus and 2.5-25% Bifidobacterium lactis and Lindley teaches that the tablets typically weigh from 5 mg to 5 g (see Lindley at page 4, lines 12-13) and the claimed concentrations of isomaltulose, it is noted “where 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” (See MPEP 2144.05 II). It is within the skill of an artisan to manipulate the amount of the active based on the intended treatment of the tablet.
Regarding the product-by process claims, note the 112b rejection. Per MPEP 2113 the claims are directed to product-by-process limitations and it is applicant’s burden to provide evidence of a structural distinction imparted by the process limitations since WO ‘545 and Lindley render the claimed product obvious.
Claim 6 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over over WO 2020252545, in view of Lindley (EP Publication No. 0028905 B1) optionally in view of WO 2008039531 in further in view of Schultz (“Rice-based excipients can boost organic, non-GMO claims for supplements”, previously presented).
The teachings of WO ‘545, WO ‘531 and Lindley have been set forth above.
However, the references do not teach the use of rice extract blend as an excipient.
Schultz’s general disclosure relates to the benefits of using rice-based excipients.
Schultz teaches that rice bran-based excipients can be used to substitute for non-organic lubrication, anti-caking, and flow agents in supplement formulations, including “a tablet or capsule”, which an artisan would readily appreciate include lozenges (see Schultz at p. 1 at para. 1-5).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reasons:
The ordinary artisan would be motivated to select rice bran-based excipients for lubrication or anti-caking (see Id.). An ordinary artisan would expect the selection or substitution for non-organic lubricant or anti-caking agents to provide predictable results and would readily improve the known probiotic product. A conclusion of obviousness can be made when: simple substitution of one known element for another obtains predictable results, use of known technique to improve similar products in the same way, and substituting equivalents known for the same purpose (see MPEP 2143 (I)(B),(C); MPEP 2144.06 (II)).
In this case, an ordinary artisan would recognize that the known rice bran-based excipients can be substituted for another lubricant or anti-caking agent (i.e., the same purpose – lubrication and anti-caking) and the use thereof is known to provide an organic alternative (i.e., an improvement to the product). The simple substitution for rice bran-based excipients would obtain predictable results and/or improve the product, since rice bran-based excipients have a well-known purpose recognized by the art.
Furthermore, it is well-within the ordinary skill in the art to arrive at selecting a known lubricant or anti-caking agent (i.e., rice bran-based excipients) and substitute it for another lubricant or anti-caking agent in a similar known probiotic product. It is further within the skill of an artisan to utilize any excipient including sweeteners and flavors depending on the desired taste.
Claims 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020252545, in view of Lindley (EP Publication No. 0028905 B1) optionally in view of WO 2008039531 further in view of Klassen (EP Publication No. 2452575 A1).
The teachings of WO ‘545, WO ‘531 and Lindley have been set forth above.
WO’545 teaches a nutraceutical probiotic tablet comprising Bifidobacterium and Lactobacillus for dysbiosis (imbalance of the bacteria in the gut) and food supplement. See abstract.
The references do not teach specific bacterial strains.
Klassen’s general disclosure relates to a nutritional composition having varying probiotic content (see Abstract). Klassen teaches the use of Streptococcus salivarius K12 as a probiotic microorganism in the nutritional composition (see Klassen at ¶[0028]). Klassen teaches the use of Lactobacillus rhamnosus LGG as a probiotic microorganism in the nutritional composition (see Klassen at ¶[0029]). The composition is used to treat gut discomfort.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reasons:
The ordinary artisan would be motivated to select Lactobacillus rhamnosus LGG as a probiotic microorganism in the nutritional composition (see Klassen at ¶[0029]). An ordinary artisan would expect the selection to provide predictable results and would readily improve the known probiotic lozenge product. A conclusion of obviousness can be made when: combining prior art element according to known methods yield predictable results, the use of known technique improves similar devices (methods, or products) in the same way, and some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings arrives at the claimed invention (see MPEP 2143 (I)(A),(C),(G)). In this case, the known probiotic lactic acid bacteria, Lactobacillus rhamnosus LGG, can be used in a nutraceutical to treat gut issues. Moreover, it is within the skill of an artisan to add other probiotics such as Streptococcus salivarius K12 for an additive effect of treating bacterial gut imbalance.
Response to Arguments
Applicant’s arguments have been considered but are moot because of the new grounds of rejection necessitated by the amendment filed 6/10/2025. However, pertinent arguments will be addressed below.
Applicant argues the prior art does not teach the amended limitation of wet granulation. Applicant argues that Lindley and WO ‘545 teach direct compression.
This argument is not found persuasive. WO ‘545 exemplifies direct compression but also teaches generally compression force to use on probiotic formulations. WO’s discussion of compression force is not limited to directed compression rather to the force generally used in the compression process so as to maintain probiotic viability. Lindley teaches directed compression but also teaches on [0023]: Preparation of the tablets of the invention can be performed using known techniques. In general, a comminuted mix of the isomaltulose and other ingredients is prepared, followed by moulding or compression. Various procedures are available to ensure proper granulation and intimate and thorough mixing of the ingredients and these procedures can be adopted as appropriate.” Thus Lindley does not teach away from wet granulation and only teaches isomaltulose does not require strict granulation techniques. WO ‘531 teaches it is within the skill of an artisan to use any technique in formulating dosage forms including prior to compression, a probiotic can be dry granulated or wet granulated or direct compression may be used. Thus, wet granulation prior to compression along with the compression force is known specifically in the field of probiotic dosage forms.
Per MPEP 2113, the applicant has the burden to provide evidence that the instant claims are structurally different than the prior art. Applicant’s Declaration is noted. Applicant attempts to demonstrate direct compression versus wet granulation followed by compression, had different effects in that the probiotic count was low and had unacceptable hardness.
The Declaration is not found persuasive. First, it is noted that WO teaches, “Compression of probiotics is a process that requires special care. The force required to generate tablets must be finely controlled so that it does not cause significant impacts on the viability of the strains present in the formulation. The greater the force applied to obtain the tablets, the greater the loss of probiotics during the manufacturing process and over the product's shelf life.” WO teaches the use of 8kn and 10 compression force. Thus, WO ‘545 teaches applicant’s unexpected result of maintaining probiotic viability. Moreover, Lindley and WO ‘531 teach the state of the art where it is known to use wet granulation prior to compression.
It is noted that the Declaration relies upon specific formulations and a narrow compression force of 7.7-7.8 kN (the claims are broadly to a probiotic microorganism and isomaltulose, compressed with a force of 6-10kN). Assuming arguendo applicant’s arguments had some merit, the claims are not commensurate in scope. See MPEP 716.03. This is of particular importance since WO ‘545 clearly teaches the excipients impact probiotic survival rate. [0031] “Physical aspects such as humidity and water activity are decisive when choosing the matrix used….so that there is no activation of probiotic microorganisms in the tablet and, thus, accelerate the degradation of the product, decreasing the potency and activity of the microorganisms. The excipients compatible with the probiotics must have other characteristics besides low water activity and controlled humidity, they must also be compressible with a low compression force, since the impact of the compression directly interferes in the viability of the probiotic strains.” [0033]. Lindley also teaches on [0003]: In order to produce tablets, it is necessary to have a free- flowing material which has good self-binding properties and which will not stick to the moulding or compression equipment. Such properties are obtained by using diluents and one or more additives, for example binders and/or lubricants, and by controlled granulation of the ingredients.” Thus clearly the art teaches the tablet properties depend on the excipients used. Applicant’s independent claim does not claim any concentration of the probiotic or isomlatulose or any of the specific excipients used in formulations provided in the Declaration. Moreover, applicant claims that the instant process of making the dosage form provides probiotic viability and acceptable physical properties. The prior art teaches preserving probiotic viability using the proper compression force; isomaltulose for its properties including binding ability and disintegrating properties, the art teaches the need to use excipients with reduced water activity in probiotic compositions; thus applicant has not provided any unexpected properties other than what is taught in the art.
Conclusion
No claims are allowed.
Correspondence Information
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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/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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