DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Claims included in prosecution are claims 1-15.
Response to Election/Restriction Requirement
Applicant’s election of Group I and an amine functional group in the reply filed on 4/6/26 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
1. Claim(s) 1-8, 10, and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sprogoe et al. (US 2012/0183616, Jul. 19, 2012) (hereinafter Sprogoe) as evidenced by Yousefi et al. (Journal of Biomolecular Structure and Dynamics, 2016, Vol. 34, No. 2, 362–375) (hereinafter Yousefi).
Sprogoe discloses a pharmaceutical composition comprising an insulin compound (Abstract). The insulin used may be a prodrug that releases the intact insulin compound (¶ [0028]). The prodrug includes compounds which may be oxidized or reduced biologically at a given functional group (¶ [0032]). Suitable functional groups include amino and hydroxylamine (satisfies claim 3) (¶ [0083]). “Functional groups” is the collective term used for "reactive functional group" (¶ [0086]). The terms "blocking group" or "capping group" are used synonymously and refer to moieties which are irreversibly connected to reactive functional groups to render them incapable of reacting with for example chemical functional groups (¶ [0088]). Insulin-releasing conditions are pH 7.4 and 37° C. (¶ [0115]). In an embodiment, the insulin compound is a prodrug (¶ [0127]). The prodrug may be contained in a depot (¶ [0130]). In an embodiment, the depot is a hydrogel or polymer matrix (satisfies matrix of claim 1) . Suitable polymers for use include hyaluronic acid and gelatin (satisfies claim 10) (¶ [0135]). Insulin can be linked through all relevant functionalities provided by the molecule, and such preferred functionalities include primary amino (satisfies claim 3) (¶ [0138]). It is desirable that almost all insulin release (>90%) has occurred before a significant amount of release of the backbone degradation products ( <10%) has taken place (¶ [0217]). Capping is used to prevent undesired side reactions (¶ [0232]). The method of making the prodrug involves capping remaining functional groups (satisfies claim 5) (¶ [0246]). The composition forms microparticles which have a diameter or between 1 and 500 micrometer (satisfies claim 6 and 14) (¶ [0259]). Fig. 8 discloses wherein most of the insulin was released after around 40 days upon incubation at pH 7.4 and 37° C (satisfies claim 8) (¶ [0374]).
Sprogoe differs from the instant claims insofar as not explicitly disclosing the instantly recited reactive functional group content.
However, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. See MPEP 2112.01(I). Sprogoe teaches a microcarrier/polymer microparticle comprising substantially the same biocompatible polymer, a polypeptide with substantially the same hydrodynamic radius and substantially the same reactive functional group, and substantially the same particle size. Therefore, one of ordinary skill in the art would reasonably conclude that the microcarrier/polymer microparticle would have a functional group content that is within the instantly claimed range.
The Office does not have the facilities for examining and comparing Applicant’s product with the product of the prior art in order to establish that the product of the prior art does not possess the same functional characteristics of the claimed product. The functional group content is descriptive and thus would be a property of the claimed composition. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the claimed products are functionally different than those taught by the prior art and to establish patentable differences. See Ex parte Phillips, 28 U.S.P.Q.2d 1302, 1303 (PTO Bd. Pat. App. & Int. 1993), Ex parte Gray, 10 USPQ2d 1922, 1923 (PTO Bd. Pat. App. & Int.) and In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977).
Regarding instant claim 2, as evidenced by Yousefi, insulin has a hydrodynamic radius ranging from 1.05 nm to 9.1 nm depending on its incubation time (Table 2). As such, the polypeptide of Sprogoe satisfies the instantly recited limitation.
Regarding the reactive functional group content recited in instant claim 4, as well as the swelling degree recited in instant claim 7, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. See MPEP 2112.01(I). Sprogoe teaches a microcarrier/polymer microparticle comprising substantially the same biocompatible polymer, a polypeptide with substantially the same hydrodynamic radius and substantially the same reactive functional group, and substantially the same particle size. Therefore, one of ordinary skill in the art would reasonably conclude that the microcarrier/polymer microparticle would have a functional group content as well as a swelling degree that is within the instantly claimed range.
The Office does not have the facilities for examining and comparing Applicant’s product with the product of the prior art in order to establish that the product of the prior art does not possess the same functional characteristics of the claimed product. The functional group content as well as the swelling degree are descriptive and thus would be a property of the claimed composition. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the claimed products are functionally different than those taught by the prior art and to establish patentable differences. See Ex parte Phillips, 28 U.S.P.Q.2d 1302, 1303 (PTO Bd. Pat. App. & Int. 1993), Ex parte Gray, 10 USPQ2d 1922, 1923 (PTO Bd. Pat. App. & Int.) and In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977).
Regarding the blocking group content recited in instant claim 4, 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)(A). As discussed above, capping groups are connected to reactive functional groups to render them incapable of reacting with, for example, chemical functional groups and are used to prevent undesired side reactions, which makes amounts thereof a result effective variable, since amounts directly impact the capping/blocking effect. Accordingly, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed amounts of blocking compound substitution to yield the desired capping/blocking effect.
Therefore, the teachings of Sprogoe as evidenced by Yousefi render obvious claims 1-8, 10, and 14.
2. Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sprogoe et al. (US 2012/0183616, Jul. 19, 2012) (hereinafter Sprogoe) in view of Tsai et al. (US 2004/0127698, Jul. 1, 2004) (hereinafter Tsai).
The teachings of Sprogoe are discussed above.
Sprogoe differs from the instantly recited claims insofar as not disclosing wherein the biocompatible polymer is crosslinked via a first and second crosslinking agents.
However, Tsai discloses a method for producing a double-crosslinked hyaluronate material using a first agent and a second agent (Abstract). Conventionally crosslinked hyaluronic acid (HA) materials have a limited resistance to biodegradation (¶ [0023]). Double-crosslinked hyaluronate material has excellent resistance to biodegradation or deterioration by hydrolysis, as well as mechanical strength and which can be more advantageously applied in vivo (¶ [0026]). The double crosslinked hyaluronate material can be obtained in a form of microsphere, matrix, or gel (¶ [0033]).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant application, to have modified the microcarrier of Sprogoe to include a double crosslinking process utilizing a first agent and a second agent motivated by the desire to achieve a hyaluronic acid material that has excellent resistance to biodegradation or deterioration by hydrolysis, as well as mechanical strength and which can be more advantageously applied in vivo as taught by Tsai. One of ordinary skill in the art would have had a reasonable expectation of success since such double crosslinked hyaluronate material can be obtained in a form of microsphere, matrix, or gel as taught by Tsai.
Therefore, the combined teachings of Sprogoe and Yousefi render obvious claim 9.
3. Claim(s) 11-13 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sprogoe et al. (US 2012/0183616, Jul. 19, 2012) (hereinafter Sprogoe) in view of Parisi et al. (Japanese Dental Science Review 56 (2020) 50–55) (hereinafter Parisi).
The teachings of Sprogoe are discussed above.
Sprogoe differs from the instantly recited claims insofar as not disclosing wherein the composition is coated with a cell adhesion inducing layer of a material such as fibronectin etc.
However, Parisi discloses that bioactivity of biomaterials is closely related to cell response in contact with them. However, shortly after their insertion, materials are soon covered with proteins that constitute the biological fluids, and which render the direct surface recognition by cells almost impossible. The control of protein adsorption at the interface is therefore desirable. Extracellular matrix (ECM) proteins are of particular interest in this sense,
due to their well-known ability to modulate cell behavior. Particularly, fibronectin (FBN) plays a leading role (Abstract). FBN and many others ECM components, possess adhesive motifs with the ability to promote cell adhesion and spreading. Thus, these molecules may be introduced on biomaterials to modify cell response. For example, the coating of substrates with increasing amount of FBN, leads to an evident promotion of cell adhesion and spreading in term of degree and speed (Sec. 2.3).
Accordingly, it would have been obvious for one of ordinary skill in the art, prior to the filing of the instant application, to have modified the microcarrier of Sprogoe to include a coating layer of cell adhesion proteins, such as fibronectin, motivated by the desire to improve cell adhesion and spreading in order to enhance/promote host cell response upon contact after administration as taught by Parisi.
Regarding the thickness of the cell adhesion-inducing layer recited in instant claim 13, 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)(A). As discussed above, the coating of substrates with increasing amount of FBN, leads to an evident promotion of cell adhesion and spreading in term of degree and speed, which makes the resulting coating thickness a result effective variable, since amounts and resultant thickness directly impact the cell adhesion and spreading effect. Accordingly, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed thickness of the cell adhesion layer to yield the desired cell adhesion and spreading effect.
Regarding the cell adhesion recited in instant claim 15, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. See MPEP 2112.01(I). Sprogoe in view of Parisi disclose a microcarrier/polymer microparticle comprising substantially the same biocompatible polymer, a polypeptide with substantially the same hydrodynamic radius and substantially the same reactive functional group, and substantially the same particle size as well as substantially the same cell adhesion-inducing layer. Therefore, one of ordinary skill in the art would reasonably conclude that the microcarrier/polymer microparticle would have substantially the same cell adhesion.
The Office does not have the facilities for examining and comparing Applicant’s product with the product of the prior art in order to establish that the product of the prior art does not possess the same functional characteristics of the claimed product. The cell adhesion of the particle descriptive and thus would be a property of the claimed composition. In the absence of evidence to the contrary, the burden is upon the applicant to prove that the claimed products are functionally different than those taught by the prior art and to establish patentable differences. See Ex parte Phillips, 28 U.S.P.Q.2d 1302, 1303 (PTO Bd. Pat. App. & Int. 1993), Ex parte Gray, 10 USPQ2d 1922, 1923 (PTO Bd. Pat. App. & Int.) and In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977).
Therefore, the combined teachings of Sprogoe and Parisi render obvious claims 11-13 and 15.
Conclusion
Claims 1-15 are rejected.
Claims 16-20 are withdrawn.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Abdulrahman Abbas whose telephone number is (571)270-0878. The examiner can normally be reached M-F: 8:30 - 5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana S. Kaup can be reached at 571-272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/A.A./Examiner, Art Unit 1612
/LEZAH ROBERTS/Primary Examiner, Art Unit 1612
Prosecution Insights