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 .
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.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/04/2026 has been entered.
Status of Claims
Claims 33, 34, 37-40, 43, 45, 47, 51, 53, 61, 63, 66-68 and 75-80 are pending. Claims 61, 63, 66-68 and 75-79 are withdrawn. Claims 33, 34, 37-40, 43, 45, 47, 51, 53 and 80 are under examination.
Withdrawn Rejection
In light of the amendments, the 35 U.S.C. 112(a) new matter rejection is hereby withdrawn.
In light of the amendments, the 35 U.S.C. 103 rejection over Frantz, Antonietta, as evidenced by Zanini is hereby withdrawn
In light of the amendments, the 35 U.S.C. 103 rejection over Frantz, Antonietta, as evidenced by Zanini, and further in view of Metz is hereby withdrawn.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 33, 34, 37-40, 43, 45, 51, 53 and 80 are rejected under 35 U.S.C. 103 as being unpatentable over Pluester et al. (US2017/0175068A1, published 06/22/2017).
Pluester teaches a method for coating a solid support which is suitable for being used in cell culture applications (see abstract). Pluester teaches incorporating cell function-modulating peptide sequences into the carrier proteins, it is possible to tailor a synthetic surface which is capable of modulating the certain functions of the cells which are cultured on the surface (see para. [0010]). Pluester teaches (a) preparing a solution of at least one carrier protein comprising, either attached thereto or as part of its amino acid sequence, at least one cell function-modulating peptide sequence, (b) heating the solution to at least 50oC and formation of soluble carrier protein aggregates, and contacting the carrier protein aggregates with the solid support (see paras. [0012]-[0014]). Pluester teaches the cell function-modulating peptide sequence can be associated to the carrier protein by means of a chemical coupling (see para. [0019]). Pluester teaches methods for coupling small peptides to larger proteins are known in the art and the cell function-modulating peptides can be coupled to carrier protein, such as an albumin, by amine-to-sulfhydryl crosslinker for creating sulfhydryl-reactive, maleimide-activated carrier proteins that may be used for coupling to cell function-modulating peptides (see para. [0033]). Additionally, SEQ ID NOS: 31 and 55 of Pluester have a C-terminal cysteine (page 15). Pluester teaches BSA is used as a carrier protein with SEQ ID NO: 1-26 and SEQ ID NO: 27-56 (see para. [0030]). Pluester teaches the peptides were suspended in PBS solution (see para. [0060]). In particular, Pluester teaches 10 mg BSA with 1 ml of 100 mM phosphate buffer was incubated at 70oC (see para. [0061]). Pluester teaches formation of soluble protein aggregates which comprise between 2 and 1000 protein molecules and the formation of aggregates comprising 2 and 1000 protein molecules means that at least 50% to more preferably at least 95% of the carrier proteins in the solution are present in an aggregated comprising 2 and 1000 protein molecules (see para. [0036]). Pluester teaches the optimum temperature to be used vary with the size and the nature of the carrier protein, and also with the composition of the solution, e.g., the concentration of salts and buffer which are added. The skilled person will readily be able to determine for a given carrier protein solution the temperature and the incubation time which are required to form soluble aggregates containing the recited number of protein molecules. Pluester teaches in Example 7 that peptides or peptide combination were coupled to BSA to provide carrier proteins and the protein solutions were heated to obtain aggregates (see para. [0072]).
With respect to the limitation of a solid gel, the instant specification has disclosed that heating the antigen/carrier protein liquid solution to form the solid antigen/carrier protein gel (see para. [0012], as filed dated 05/20/2024). Thus, the heating of BSA would produce a solid protein gel (see above).
With respect to the limitation of a “a polypeptide antigen”, the instant specification has disclosed that “the term ‘polypeptide’ or ‘protein’ are used interchangeably herein to refer to polymers of amino acids of any length” (see para. [0067], as filed 05/20/2024). Thus, the sequences of Pluester (see above) would read on the claimed purified antigen is a polypeptide antigen comprising a C-terminal cysteine.
The limitations of “using a cysteine-reactive reagent” and “the solid gel has been formed in the presence of a crosslinking fixative after the C-terminal cysteine is cross-linked to the carrier protein using a cysteine-reactive reagent” are product-by-process limitations. In this case, the “cysteine-reactive reagent” and “cross-linking fixative” are not an element that is part of the final product of the solid gel and Pluester teaches the cell function-modulating peptides can be coupled to carrier protein, such as an albumin, by amine-to-sulfhydryl crosslinker for coupling to cell function-modulating peptides (see para. [0033]). MPEP 2113 states that if the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.
“[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) (Claim was directed to a novolac color developer. The process of making the developer was allowed. The difference between the inventive process and the prior art was the addition of metal oxide and carboxylic acid as separate ingredients instead of adding the more expensive pre-reacted metal carboxylate. The product-by-process claim was rejected because the end product, in both the prior art and the allowed process, ends up containing metal carboxylate. The fact that the metal carboxylate is not directly added, but is instead produced in-situ does not change the end product.). Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009). However, in the context of an infringement analysis, a product-by-process claim is only infringed by a product made by the process recited in the claim. Id. at 1370 ("a product in the prior art made by a different process can anticipate a product-by-process claim, but an accused product made by a different process cannot infringe a product-by-process claim"). MPEP 2113.
Even though Pluester teaches the peptide is coupled to BSA by crosslinking, the reference does not explicitly teach a C-terminal cysteine cross-linked to the carrier protein.
However, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have used the C-terminal cysteine of the cell function-modulating peptide sequences of Pluester for crosslinking with the carrier protein and would have reasonably expected success because Pluester teaches amine-to-sulfhydryl crosslinker methods for coupling small peptides to larger proteins are known in the art and the cell function-modulating peptides can be coupled to carrier protein by amine-to-sulfhydryl crosslinker.
With respect to claim 34, Pluester teaches the formation of soluble carrier protein aggregates comprising between 2 to 1000 protein molecules (see abstract). However, Pluester does not explicitly teach the solid gel thickness of about 30nm to about 50µm.
However, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable in producing an aggregated gel for attachment. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the concentrations recited in the claims are for any particular purpose or solve any stated problem. As stated, Pluester teaches soluble carrier protein aggregates comprising between 2 to 1000 protein molecules for cells. It would have been obvious for the person of ordinary skill to discover the optimum effective thickness for cell attachment through aggregating carrier protein molecules. Additionally, Pluester teaches aggregating between 2 to 1000 protein molecules and peptides. Meanwhile, the claim only requires antigen crosslinked with a gel substrate consisting of a carrier protein. Because the claimed range overlaps with the range disclosed by the prior art, a prima facie case of obviousness exists.
With respect to claims 37-40, Pluester teaches the protein aggregates obtained in step (b) are lyophilized (see para. [0041]). It is noted that the claimed limitations of “is frozen in an embedding medium”, is embedded in paraffin”, “is embedded in a plastic resin”, and “is affixed to solid substrate” are directed to the intended use of the claimed solid antigen/carrier protein.
MPEP 2114 II states that “ ‘[A]pparatus claims cover what a device is, not what a device does.’ Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987) (The preamble of claim 1 recited that the apparatus was "for mixing flowing developer material" and the body of the claim recited "means for mixing ..., said mixing means being stationary and completely submerged in the developer material." The claim was rejected over a reference which taught all the structural limitations of the claim for the intended use of mixing flowing developer. However, the mixer was only partially submerged in the developer material. The Board held that the amount of submersion is immaterial to the structure of the mixer and thus the claim was properly rejected.)” (Emphasis added).
In this particular case, the recitation of the intended use of the claimed invention must result in a structural difference between the claimed solid gel of carrier protein and the prior art’s aggregated protein structure in order to patentably distinguish the claimed invention from the prior art. If the prior art’s aggregated protein structure teaches all the structural limitations of the claimed solid gel, then it meets the claim. Because the prior art’s aggregated protein structure reads on the claimed structure of the solid gel, the prior art’s solid gel would be capable of performing the recited intended uses. Thus, the reference meets the claims.
With respect to claim 43, the limitations of “the solid gel has been formed in the presence of a crosslinking fixative after the C-terminal cysteine is cross-linked to the carrier protein using a cysteine-reactive reagent” are product-by-process limitations. In this case, the “cross-linking fixative” is not an element that is part of the final product of the solid gel and Pluester teaches the cell function-modulating peptides can be coupled to carrier protein, such as an albumin, by amine-to-sulfhydryl crosslinker for coupling to cell function-modulating peptides (see para. [0033]). MPEP 2113 states that if the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. Thus, the reference meets the claim.
With respect to 45, it is noted that the claimed limitation of “wherein the solid gel has been subjected to antigen retrieval” is directed to the intended use of the claimed solid antigen/carrier protein.
MPEP 2114 II states that “ ‘[A]pparatus claims cover what a device is, not what a device does.’ Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990) (emphasis in original). A claim containing a "recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus" if the prior art apparatus teaches all the structural limitations of the claim. Ex parte Masham, 2 USPQ2d 1647 (Bd. Pat. App. & Inter. 1987) (The preamble of claim 1 recited that the apparatus was "for mixing flowing developer material" and the body of the claim recited "means for mixing ..., said mixing means being stationary and completely submerged in the developer material." The claim was rejected over a reference which taught all the structural limitations of the claim for the intended use of mixing flowing developer. However, the mixer was only partially submerged in the developer material. The Board held that the amount of submersion is immaterial to the structure of the mixer and thus the claim was properly rejected.)” (Emphasis added).
In this particular case, the recitation of the intended use of the claimed invention must result in a structural difference between the claimed solid gel of carrier protein and the prior art’s aggregated protein structure in order to patentably distinguish the claimed invention from the prior art. If the prior art’s aggregated protein structure teaches all the structural limitations of the claimed solid gel, then it meets the claim. Because the prior art’s aggregated protein structure reads on the claimed structure of the solid gel, the prior art’s solid gel would be capable of performing the recited intended uses. Thus, the reference meets the claims.
With respect to claim 51, Pluester teaches 10 mg BSA with 1 ml of 100 mM phosphate buffer was incubated at 70oC (see para. [0061]).
With respect to claim 53, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable in producing an aggregated gel. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the concentrations recited in the claims are for any particular purpose or solve any stated problem. As stated, Pluester teaches soluble carrier protein aggregates comprising between 2 to 1000 protein molecules for cells. Thus, it would have been obvious for the person of ordinary skill to discover the optimum effective BSA concentration to form an aggregate gel.
With respect to claim 80, the limitations of “the solid gel has been formed in the presence of a crosslinking fixative after the C-terminal cysteine is cross-linked to the carrier protein using a cysteine-reactive reagent” and “wherein the cross-linking fixative is an aldehyde-based fixative” are product-by-process limitations. In this case, the “cross-linking fixative” is not an element that is part of the final product of the solid gel and Pluester teaches the cell function-modulating peptides can be coupled to carrier protein, such as an albumin, by amine-to-sulfhydryl crosslinker for coupling to cell function-modulating peptides (see para. [0033]). MPEP 2113 states that if the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. Thus, the reference meets the claim.
Claims 33, 34, 37-40, 43, 45, 51, 53 and 80 are rejected under 35 U.S.C. 103 as being unpatentable over Pluester et al. (US2017/0175068A1, published 06/22/2017) in view of Sompuram et al. (“Antibodies Immunoreactive With Formalin-Fixed Tissue Antigens Recognize Linear Protein Epitopes”, American Journal Clinical Pathology (Am J Clin Pathol), vol. 125, pgs. 82-90, published 2006).
Pluester has been discussed above. For compact prosecution, the reference does not explicitly teach crosslinking fixative (claim 33) wherein the crosslinking fixative comprises formaldehyde (claim 43) and wherein the crosslinking fixative is an aldehyde-based fixative (claim 80).
Sompuram teaches the findings are the first detailed studies of antibody epitopes associated with antigen retrieval and suggest that antibodies must recognize linear sequences to bind after formalin fixation and antigen retrieval (see abstract). Sompuram teaches the slides then rinsed and the remaining reactive isocyanate groups with a protein cocktail containing bovine gamma globulins (see pg. 83, right col., para. 3). Pluester teaches most prevalent amino acids, glutamine and tyrosine, are both capable of chemically reacting with certain other amino acids in the presence of formaldehyde (see pg. 89, left col., para. 2, Fig. 4). Sompuram teaches it is well known that formaldehyde is capable of chemically reacting with numerous amino acids, causing them to cross-link and thereby denature the protein (see pg. 87, right col., last para.).
Thus, it would have been obvious to have used the aggregated protein coupled to peptide as taught by Pluester with formaldehyde as taught by Sompuram because Sompuram teaches that it is well known in the art that formaldehyde is capable of chemically reacting with numerous amino acids and prevalent glutamine and tyrosine are chemically cross-linking in the presence of formaldehyde and Pluester teaches the presence of glutamine and tyrosine amino acids are in the function-modulating peptide sequence. Thus, it would have been obvious to the person to have used the well-recognized formaldehyde to cross reacted with BSA to anchor the attachment of the peptide sequences to BSA.
The person would have a reasonable expectation of success in the function-modulating peptide sequences with formaldehyde because it was been well recognized in the art to use formaldehyde with glutamine and tyrosine amino acids.
With respect to claim 43, although Sompuram teaches formaldehyde is an effective crosslinker, the reference does not explicitly teach formaldehyde at a concentration of at least about 1%. However, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value for a result effective variable in amino acid crosslinking. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation” Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). “No invention is involved in discovering optimum ranges of a process by routine experimentation.” Id. at 458, 105 USPQ at 236-237. The “discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” Since applicant has not disclosed that the concentrations recited in the claims are for any particular purpose or solve any stated problem. Thus, it would have been obvious for the person of ordinary skill to discover the optimum effective formaldehyde concentration to crosslink the peptide’s amino acids and BSA.
Claim 47 is rejected under 35 U.S.C. 103 as being unpatentable over Pluester et al. in view of Sompuram et al., as applied to claim 33 above, and further in view of Davis et al. (US2016/0238596A1, published 08/18/2016).
Pluester and Sompuram have been discussed above. However, the references do not explicitly teach the polypeptide antigen further comprises an N-terminal tyrosine and the N-terminal tyrosine is cross-linked to the carrier protein.
Davis teaches in SEQ ID NO: 4 a N-terminal tyrosine and C-terminal cysteine. Davis teaches BES buffer at pH 7.8 and BSA was used as a blocking solution (see para. [0156]). Davis teaches an indicator molecule (usually a peptide) to produce a novel and specific binding site for a binding molecule (usually an antibody binding to a newly revealed or produced epitope) (see para. [0045]). Davis teaches in Fig. 5 terminal amino acid crosslinking.
Thus, it would have been obvious to the person to have used/incorporated the cell function-modulating peptide sequence of Pluester with a N-terminal tyrosine of Davis because teaches that crosslinking at the terminal ends of the peptide. Thus, it would have been obvious to have incorporated tyrosine at the N-terminal end of the peptide for cross reaction because it provides the ability for the peptide to attach to cell based on the sequence.
The person would have a reasonable expectation of success of using SEQ ID NO: 4 or incorporating tyrosine at the N-terminal end because it has been well understood by the references to use peptide sequences for attachments.
Response to Arguments
Applicant’s arguments filed 06/04/2026 have been considered but are moot because Applicant’s amendments necessitated a new ground of rejection.
Conclusion
No claim is allowed.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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