DETAILED ACTION
Note that the Examiner for this application has changed.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/12/2025 has been entered.
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 .
Status of the Claims
Claims 1-20 are pending (claim set as filed on 12/12/2025).
Applicant’s election with traverse of Group I is again acknowledged. Claims 9-15 and 18-19 stand withdrawn as being directed to the non-elected invention.
Therefore, only claims 1-8, 16-17, and 20 are under examination.
Priority
This application is a 371 of PCT/EP2020/079901 filed on 10/23/2020, which has a foreign application to EP 19306387.2 filed on 10/25/2019.
Withdrawal of Rejections
The response and amendments filed on 12/12/2025 are acknowledged. Any previously applied minor objections and/or minor rejections, not explicitly restated herein for brevity, have been withdrawn necessitated by Applicant’s formal corrections and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining if applicable, of the essential claim rejections are detailed below in the Examiner’s response to arguments section.
Briefly, the previously applied §112(a) new matter rejection has been withdrawn necessitated by Applicant’s showing of support in the instant specification at page 33 (or the pre-grant publication at ¶ [0139]).
Briefly, the previously applied §112(b) indefinite rejection has been withdrawn necessitated by Applicant’s amendments to clarify the claims.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Maintained Rejections
Claim Rejections - 35 USC §103, Obviousness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-8, 17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Glibitskiy (Textures on the surface of BSA films with different concentrations of sodium halides and water state in solution, 2015) in view of Wang (Silk nanospheres and microspheres from silk/pva blend films for drug delivery, 2010) and Uehlin (US 2015/0073551 A1) - all references previously cited.
Glibitskiy general disclosure relates to the formation of biofilms from bovine serum
albumin (BSA) with sodium halides and the texture thereof (see abstract). The reference teach the state of the art in which NaCl was studied and the texture of the film decreased with the concentration of NaCl. KaCl also produced similar structures with BSA and generally the formation of the structures are due to certain range of concentrations of biopolymer and salt. (see page 1, right col.). Specifically, Glibitskiy discusses the results in the texture of the films using different concentrations. Glibitskiy discloses a process of preparing a biomaterial comprising: preparing a solution comprising a protein, bovine albumin serum (BSA), and a salt, NaBr, and drying the solution at 40°C (see Glibitskiy at Abstract; at page 1 at 1st ¶; at page 2
at 5th-10th ¶; at page 4 at Figure 4 and 6). Glibitskiy ‘s process yields a film; i.e. a dry solid. Glibitskiy discloses the solution comprising 0.5 mg/mL (7.5x10-3mM) of BSA and 20 mM (2g/mL) of NaBr (see Glibitskiy at page 2 at 5th-6th ¶).
Examiner’s note: the molar ratio of salt/protein is about 2657 (as confirmed by Applicant’s remarks of 6/3/2025). Also noted the term “insoluble” is given it broadest reasonable interpretation absent any parameters limiting the term (i.e. degradation rates). The 132 Declaration, Figure 1 demonstrates a deposit remains after washing.
However, Glibitskiy does not teach: salt/serum protein molar ratio of 200 to 2000 (claim 1(a) limitation); the process is done under atmospheric pressure (claim 1(b) limitation); or a washing step (claims 1(c) limitation and 3); or polymers/additives used (claims 6-7 and 17).
Wang’s general disclosure relates to a silk fibroin protein-based micro/nano-spheres for
drug delivery and associated silk/polyvinyl alcohol biofilms (see Wang at Abstract). Wang teaches silk fibroin, BSA, PVA (polymer additive -reads on instant claim 7) and PBS buffer (PBS contains KH2PO4) to yield a biomaterial followed by rinsing in water. Wang teaches washing of silk/PVA blends with water produced the surface of the biofilms or biospheres to become porous which provided unique drug loading and release properties (see Wang at page 1029 at Section 3.1 at 2nd ¶; at Figure 1). Wang teaches the use of silk as a protein and LiBr as a salt (see Wang at page 1026 at Section 2.2), PVA is an additive in the biomaterial preparation process (see Wang at page 1026 at Section 2.3). Wang teaches polymers such as PVA are used to manipulate film degradation. See page 1026
Uehlin teaches a process of making a biomaterial film comprising PLA, salt and a polypeptide such as fibrin. The film is washed to remove the salt and any solvents, and air dried at room temperature (see ¶ [0090]). Uehlin teaches the use of various polymers in order to manipulate the biodegradation of material (see ¶ [0081]). Uehlin teaches degradation rate can vary by altering factors such as structural configuration, morphology, stresses, crystallinity, molecular weight, copolymer ratio, amount of residual monomer, porosity and site of implantation, and the like, by methods well known to those in the art. Uehlin teaches the use of salt to manipulate the porosity of the film (see ¶ [0090]).
First although Glibitskiy does not specify the process is done under atmospheric pressure, it would reasonable to presume that the method of Glibitskiy to work at atmospheric pressure in addition to multiple different pressures. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the instantly claimed invention in view of the prior art for at least the following reasons:
An ordinary artisan would have reasonably assumed that the evaporation step of
Glibitskiy was necessarily performed at atmospheric pressure, absent of any mention of the
usage of a specialized pressure or mention of any specialized equipment or steps required to
obtain a different pressure in order to replicate the published results. A conclusion of
obviousness can be made when the claimed invention is the results of combining prior art elements according to known methods to yield predictable results (see MPEP § 2143 (I)(A)
and/or when routine optimization can arrive at the prior art conditions (see MPEP § 2144.05
(II)). In this case, preparing a solution and evaporating the solution as taught by Glibitskiy are
known methods that would yield the predictable results of obtaining a biomaterial. Additionally, by routine optimization, an ordinary artisan would arrive at the prior art conditions, notably the pressure of the evaporation step. Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§2123(I)-(II)). An artisan would have reasonable expectation of success because it is well-within the ordinary skill in the art to use known methods of preparing a solution comprising a protein and evaporating the solution to achieve only the predicted, expected, and art-recognized results, which includes obtaining a biomaterial.
Second, although Glibitskiy does not teach the amended range of salt to serum protein, Glibitskiy teaches the salt to protein ratio changes the texture of the film and thus, manipulation of the ratio to yield the desired film is prima facie obvious to one of ordinary skill. Uehlin teaches salt is used to manipulate the porosity. It is clear the prior art teaches the manipulation of the concentration of the components provides the desired properties including biodegradation, porosity, surface texture, etc. The manipulation of the concentration of salt and protein is a result effect variable and it is within the skill of an artisan to discover the optimum or workable ranges by routine experimentation, absent evidence otherwise.
Third it would have been obvious to one of ordinary skill in the art to combine the above teachings of Glibitskiy, Wang, and wash the biomaterial. An ordinary artisan would have motivated to wash away salts to increase porosity which provides unique drug loading and release properties as taught by Wang (see Wang at page 1029 at Section 3.1 at 2nd ¶; at Figure 1). Further, it is noted that Uehlin demonstrates it is known in the art to utilize a wash step to remove any residual components that are not needed (see Uehlin at ¶ [0090]). A conclusion of obviousness can be made when the claimed invention is the results of using a known technique to improve a similar device, method, or product in the same way and/or applying a known technique to a known device, method, or product ready for improvement to yield predictable results (see MPEP § 2143 (I)(C),(D)). In this case, washing a biomaterial is a known technique that can be used to improve the known method and/or known biomaterial as taught by Glibitskiy to yield a predictable improvement to the porosity of the biomaterial for adhesion and release of drugs and removal of residual components including salts, solvents, etc. An artisan would have reasonable expectation of success because it is well within the ordinary skill in the art to use the known technique of washing in the preparation of a biomaterial to achieve the predicted, expected, and art-recognized results, which includes increased porosity and better adhesion and release of drugs. Further, one of ordinary skill in the art would recognize washing away salts from the biomaterial as advantageous to remove unnecessary components. In view of the guidance of Wang, an artisan would readily appreciate that washing steps could be continued or repeated until the %wt of a particular component had been reduced to a desirable level (e.g., claim 3). The degree of washing is within the skill of an ordinary artisan to achieve and optimize. 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” (MPEP 2144.05 II).
Regarding claims 6-7 and 17 pertaining to the additive, Wang and Uehlin teaches the addition of polymers to manipulate the degradation of the film. Therefore, it would have been obvious to utilize an additional polymer in order to yield a film with the desired degradation.
Regarding claim 20 pertaining to the weight percentage of proteins, the MPEP 2111.04 states that a wherein or whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.
Claims 1-8, 16-17, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Glibitskiy in view of Wang and Vikinge (WO 2010/138062 A1) - all references previously cited.
Glibitskiy general disclosure relates to the formation of biofilms from bovine serum
albumin (BSA) with sodium halides and the texture thereof (see Abstract). The reference teach the state of the art in which NaCl was studied and the texture of the film decreased with the concentration of NaCl. KaCl also produced similar structures with BSA and generally the formation of the structures are due to certain range of concentrations of biopolymer and salt. See page 1, right column. Specifically, Glibitskiy discusses the results in the texture of the films using different concentrations. Glibitskiy discloses a process of preparing a biomaterial comprising: preparing a solution comprising a protein, bovine albumin serum (BSA), and a salt, NaBr, and drying the solution at 40°C (see Glibitskiy at Abstract; at page 1 at 1st ¶; at page 2
at 5th-10th ¶; at page 4 at Figure 4 and 6). Glibitskiy’s process yields a film; i.e. a dry solid. Glibitskiy discloses the solution comprising 0.5 mg/mL (7.5x10-3mM) of BSA and 20 mM (2g/mL) of NaBr (see Glibitskiy at page 2 at 5th-6th ¶).
Examiner’s note: the molar ratio of salt/protein is about 2657 (as confirmed by Applicant’s remarks of 6/3/2025). Also noted the term “insoluble” is given it broadest reasonable interpretation absent any parameters limiting the term (i.e. degradation rates). The 132 Declaration, Figure 1 demonstrates a deposit remains after washing.
However, Glibitskiy does not teach: salt/serum protein molar ratio of 200 to 2000 (claim 1(a) limitation); the process is done under atmospheric pressure (claim 1(b) limitation); or a washing step (claims 1(c) limitation and 3); or polymers/additives used (claims 6-7 and 17); or the use of a globulin (claim 16).
Wang’s general disclosure relates to a silk fibroin protein-based micro/nano-spheres for
drug delivery and associated silk/polyvinyl alcohol biofilms (see Wang at Abstract). Wang teaches silk fibroin, BSA, PVA (polymer additive -reads on instant claim 7) and PBS buffer (PBS contains KH2PO4) to yield a biomaterial followed by rinsing in water. Wang teaches washing of silk/PVA blends with water produced the surface of the biofilms or biospheres to become porous which provided unique drug loading and release properties (see Wang at page 1029 at Section 3.1 at 2nd ¶; at Figure 1). Wang teaches the use of silk as a protein and LiBr as a salt (see Wang at page 1026 at Section 2.2), PVA is an additive in the biomaterial preparation process (see Wang at page 1026 at Section 2.3). Wang teaches polymers such as POA are used to manipulate film degradation. See page 1026
Vikinge teaches a method of making a protein film for drug delivery and biomedical implants. Vikinge teaches “the protein film may be formed of any suitable protein and one of ordinary skill in the art will appreciate that the protein will be selected depending on the desired use of the protein film.” The protein may be selected from various proteins known in the art including fibrinogen, albumin, for example serum albumin, fibronectin, vitronectin, globulin, for example immunoglobulin (IgA, IgD, IgE, IgG, IgM), or a mixture of two or more thereof. [0020] It is noted that Vikinge teaches the routine nature of manipulating the concentrations of the protein and the components used in the film such as buffers and salts. Vikinge teaches the protein concentration in the solution may be varied and typically higher solution concentrations will result in thicker films. The protein solution may comprise protein in an amount of from about 0.1 mg/ml to about 300 mg/ml, from about 1 mg/ml to about 100 mg/ml, from about 1 mg/ml to about 10 mg/ml, and from about 1 mg/ml to about 5 mg/ml. The protein solution may be buffered and suitable buffers include, but are not limited to, acetate buffers, borate buffers, citrate buffers or phosphate buffers in a range of from about 0.1 mM to about 100 mM, or from about 1 mM to about 50 mM or, more specifically, from about 5 mM to about 30 mM. In further embodiments, the protein solution contains salt, and has a concentration of from about 0.1% w/v to about 10% w/v, or more specifically from about 0.5% w/v to about 2% w/v. [0035]. Vikinge teaches the routine nature of forming a biomaterial and rinsing the end product. See examples.
First although Glibitskiy does not specify the process is done under atmospheric pressure, it would reasonable to presume that the method of Glibitskiy to work at atmospheric pressure in addition to multiple different pressures. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the instantly claimed invention in view of the prior art for at least the following reasons:
An ordinary artisan would have reasonably assumed that the evaporation step of
Glibitskiy was necessarily performed at atmospheric pressure, absent of any mention of the
usage of a specialized pressure or mention of any specialized equipment or steps required to
obtain a different pressure in order to replicate the published results. A conclusion of
obviousness can be made when the claimed invention is the results of combining prior art elements according to known methods to yield predictable results (see MPEP § 2143 (I)(A)
and/or when routine optimization can arrive at the prior art conditions (see MPEP § 2144.05
(II)). In this case, preparing a solution and evaporating the solution as taught by Glibitskiy are
known methods that would yield the predictable results of obtaining a biomaterial. Additionally, by routine optimization, an ordinary artisan would arrive at the prior art conditions, notably the pressure of the evaporation step. An artisan would have reasonable expectation of success because it is well-within the ordinary skill in the art to use known methods of preparing a solution comprising a protein and evaporating the solution to achieve only the predicted, expected, and art-recognized results, which includes obtaining a biomaterial.
Second, although Glibitskiy does not teach the amended range of salt to serum protein, Glibitskiy teaches the salt to protein ratio changes the texture of the film and thus, manipulation of the ratio to yield the desired film is prima facie obvious to one of ordinary skill. Further Vikinge teaches the manipulation of the salt and protein concentration to yield a film with desired properties. It is clear the prior art teaches the manipulation of the concentration of the components provides the desired properties including biodegradation, film thickness, surface texture, and etc. The manipulation of the concentration of salt and protein is a result effect variable and it is within the skill of an artisan to discover the optimum or workable ranges by routine experimentation, absent evidence otherwise.
Third it would have been obvious to one of ordinary skill in the art to combine the above teachings of Glibitskiy, Wang, and wash the biomaterial. An ordinary artisan would have motivated to wash away salts to increase porosity which provides unique drug loading and release properties as taught by Wang (see Wang at page 1029 at Section 3.1 at 2nd ¶; at Figure 1). A conclusion of obviousness can be made when the claimed invention is the results of using a known technique to improve a similar device, method, or product in the same way and/or applying a known technique to a known device, method, or product ready for improvement to yield predictable results (see MPEP § 2143 (I)(C),(D)). In this case, washing a biomaterial is a known technique that can be used to improve the known method and/or known biomaterial as taught by Glibitskiy to yield a predictable improvement to the porosity of the biomaterial for adhesion and release of drugs and removal of residual components including salts, solvents, etc. An artisan would have reasonable expectation of success because it is well- within the ordinary skill in the art to use the known technique of washing in the preparation of a biomaterial to achieve the predicted, expected, and art-recognized results, which includes increased porosity and better adhesion and release of drugs. Further, one of ordinary skill in the art would recognize washing away salts from the biomaterial as advantageous to remove unnecessary components. In view of the guidance of Wang, an artisan would readily appreciate that washing steps could be continued or repeated until the %wt of a particular component had been reduced to a desirable level. The degree of washing is within the skill of an ordinary artisan to achieve and optimize. 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).
Regarding claims 6-7 and 17 pertaining to the additive, Wang teaches the addition of polymers to manipulate the degradation of the film. Therefore, it would have been obvious to utilize an additional polymer in order to yield a film with the desired properties including degradation rate.
Regarding claim 16 pertaining to the globulin, Vikinge teaches the combination of proteins including albumin and globulin. It would have been obvious to one of ordinary skill in the art to combine the above teachings and utilize globulin, in addition to, or in the place of albumin, in the biomaterial. Thus, one of ordinary artisan would have motivated to utilize any protein of choice depending on the desired end result of the film’s properties including texture, thickness, etc., as taught by Vikinge.
Regarding claim 20 pertaining to the weight percentage of proteins, the MPEP 2111.04 states that a wherein or whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.
Examiner’s Response to Arguments
Applicant’s arguments filed on 12/12/2025 have been fully considered but they are not persuasive and deemed insufficient to overcome the prior arts of record.
(I) §103 Obviousness Rejection over Glibitskiy in view of Wang and Uehlin
In response to Applicant’s argument (addressing adjoining pages 6-7 of the remarks) that one of ordinary skill in the art would have no reason to eliminate/remove the salts via washing from Glibitskiy’s disclosure as it would change the principle and purpose of Glibitskiy’s process: this argument is not persuasive because a washing step would not change Glibitskiy’s principle operation. The objective of Glibitskiy is investigational studies of textures on the surface of BSA films with different concentrations of sodium halides and water state in solution (see Glibitskiy’s title & abstract). However, note the base claim’s transitional phrase of “comprising” is open-ended and does not exclude additional, unrecited elements or method steps (MPEP 2111.03(I)) and thus, a washing step such as taught by the secondary references may be performed after the Glibitskiy’s investigational studies. There is no teaching in Glibitskiy that criticizes, discredits, or otherwise discourages a washing step.
In response to Applicant’s argument (addressing page 7 of the remarks) that the secondary references of Wang and Uehlin are directed to different methods of making products distinct from Glibitskiy, and there is no reason why the skilled person would consider these references together: this argument is not persuasive because, as discussed in the prior office action, “A conclusion of obviousness can be made when the claimed invention is the results of combining prior art elements according to known methods to yield predictable results” (MPEP 2143(I)(A) and/or when routine optimization can arrive at the prior art conditions (MPEP 2144.05 (II)). Therefore, the secondary references demonstrated well-known, common, and routine expedients or practices in the art such that the claimed parameters are considered within the skill of an artisan to discover the optimum or workable ranges by routine experimentation. The secondary references further provided reasons to change the claimed parameters such as the manipulation of the concentration of the components provides the desired properties including biodegradation, porosity, surface texture, etc. (see prior office action on page 9). Uehlin demonstrates it is known in the art to utilize a wash step to remove any residual components that are not needed (see Uehlin at ¶ [0090]). One cannot show non-obviousness by attacking references individually where the rejections are based on combinations of references (MPEP 2145(IV)).
(II) §103 Obviousness Rejection over Glibitskiy in view of Wang and Vikinge (‘062)
In response to Applicant’s argument (addressing page 7 of the remarks) that Vikinge ‘062 is directed to making films using temperatures over 60°C which would lead to irreversible denaturation and alterations of the material’s structure, result in loss of properties, and trigger inflammation: this argument is not persuasive because the primary reference of Glibitskiy already taught the temperature limitations. In particular, Glibitskiy discloses a process of preparing a biomaterial comprising: preparing a solution comprising a protein, bovine albumin serum (BSA), and a salt, NaBr, and drying the solution at 40°C (see Glibitskiy at abstract; at page 1 at 1st ¶; at page 2 at 5th-10th ¶; at page 4 at Figure 4 and 6). Vikinge ‘062 was relied upon to teach the salt and protein concentrations and the use of globulin. Furthermore, the MPEP 2144.05(II)(A) states that “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. 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”.
Conclusion
No claims were allowed.
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653