DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicants’ Amendment
1) Acknowledgment is made of Applicants’ amendment filed 05/19/26 in response to the non-final Office Action mailed 02/19/26.
Status of Claims
2) Claims 1 and 20 have been amended via the amendment filed 05/19/2026.
Claims 1-7, 13 and 15-20 are pending.
Claims 1-4, 13 and 15-20 are under examination.
Prior Citation of Title 35 Sections
3) The text of those sections of Title 35 U.S. Code not included in this action can be found in a prior Office Action.
Prior Citation of References
4) The references cited or used as prior art in support of one or more rejections in the instant Office Action and not included on an attached form PTO-892 or form PTO-1449 have been previously cited and made of record.
Rejection(s) Withdrawn
5) The rejection of claims 1-4, 11, 13 and 15-20 set forth in paragraph 10 of the Office Action mailed 02/19/26 under 35 U.S.C § 112(a) or 35 U.S.C § 112 (pre-AIA ), first paragraph, with regard to the written description issue is withdrawn in light of Applicants’ claim amendment. A new/modified rejection is set forth in this Office Action to address the claims as amended.
Applicants submit the following arguments:
The U.S. Court of Appeals for the Federal Circuit (CAFC) on April 16, 2026 issued a decision in Teva Pharmaceutical International GMBH v. Eli Lilly and Company (No. 2024-1094 (Fed. Cir. 2026), hereafter "Teva"), which concerns, inter alia, the written description requirement of 35 U.S.C. § 112. The written description dispute concerned whether the patent's specification disclosed a representative number of species of the asserted claims' genus of humanized anti-CGRP antagonist antibodies (Id., paragraph bridging pages 8-9). In its decision, the court discusses several prior decisions as instructive for analyzing written description in circumstances where a claim pertains to a well-known genus that is not, itself, the invention (Id., page 9). In finding that the claims to a method of treating headache with a humanized monoclonal anti-CGRP antagonist antibody to satisfy the written description (and enablement) requirements, the court found that "when a genus is well understood in the art and not itself the invention but is instead a component of the claim, background knowledge may provide the necessary support for the claim" (Id., page 12). Such is the case here.
The instant claims are to an enzymatic extraction agent in the form of a lyophilized or dried composition comprising (i) a recombinant PlyC comprising a PlyCA gene product and a PlyCB gene product, and (ii) a labeled antibody that specifically binds to a Group A Streptococcus- specific antigen. Like the claims at issue in Teva, the instant claims define an invention that applies a genus that are themselves not the invention but merely a component of the invention. According to the Teva decision, that the claimed invention can use various members of the recited genus of PlyCA and PlyCB gene products does not require that every PlyCA or PlyCB gene product be disclosed, just as a method of treating headache with a humanized monoclonal anti-CGRP antagonist antibody did not require disclosure of every possible antibody in the genus of antibodies, so long as that genus is well understood and is not itself the invention. Here, a genus of PlyCA and PlyCB gene products is well understood because such gene products have structural features in common so that a skilled person can recognize members of the genus. Further, determining a sequence of such a gene product not already known in available databases or in the scientific literature is routine to an ordinarily skilled artisan. The PlyCA and PlyCB gene products themselves are merely a component of the claimed method which is well described in the application as filed.
Applicants’ arguments have been considered, but are not persuasive.
Instant claims are distinguished from the ones involved in Teva vs Eli Lilly. In Teva vs Eli Lilly, the appellate court held that, in the context of these method claims, the specification and background knowledge in the field were sufficient for a reasonable jury to find that the written description and enablement requirements were met. The court emphasized that the invention concerned the use of a well-known genus of antibodies for a specific purpose, and the specification indicated that all members of the genus would function as claimed. Instant claims however are directed to a product: “An enzymatic extraction agent” comprising (i) a recombinant PlyC comprising a PlyCA gene product and a PlyCB gene product, and (ii) a labeled antibody that specifically binds to a Group A Streptococcus-specific antigen. For example, see claim 1. The recombinant PlyC as claimed is not an inert component, instead an essential component of the claimed product that is required for the extracting function in the claimed enzymatic extraction agent. The PlyCA gene product and the PlyCB gene product are not ‘mere’ components of the claimed product, but are a part of the recited PlyC element that is required and necessary for the claimed product to work as intended.
Claims are interpreted in light of the specification to ensure they accurately reflect the true scope of the invention as disclosed. Under MPEP § 2111, the USPTO must give claims their broadest reasonable interpretation (BRI) consistent with the specification.
The recited recombinant PlyC genus as expressly defined in the as-filed specification encompasses ‘mutants’ and ‘derivatives’ of PlyC having up to 70% identity or homology to PlyC protein. Said PlyC genus encompassing said structurally highly divergent mutants and derivatives having the requisite function(s) was not well understood at the time of the invention. Less than full-length PlyC species including PlyC oligopeptide species are encompassed within the claimed genus. A representative number and variety of these mutant species and derivative species having up to 30% non-identity to PlyC as well as peptide and oligopeptide species of PlyC having the requisite function(s) are not described in the as-filed specification, nor have Applicants provided any evidence showing that said structurally highly diverse species existed in the field or scientific literature at the time of the invention.
In sum, the rejection of record sets forth a detailed analysis explaining the scope of the claims, the scope of the broad variable genus, the genus-species issues, the art-recognized unpredictability issue, and the lack of possession at the time of the invention issue along with the interpretation of instant claims based on the express definitions and descriptions within Applicants’ as filed specification. It is noted again that Applicants have advanced no arguments with regard to the cited references of Skolnick et al. Trends in Biotechnology 18: 34-39, 2000 (of record), Rudinger J. (In: Peptide Hormones. (Ed) JA Parsons, University Park Press, pages 1-7, 1976, of record), Seffernick et al. (J. Bacteriol. 183: 2405-2410, 2001), Lazar et al (Mol. Cellular Biol. 8: 1247-1252, 1988), and Mikayama et al. (Proc. NatI. Acad. Sci. USA, 90: 10056-10060, 1993), the teachings of which are used to establish the issue of art-recognized unpredictability in the absence of a showing possession within the as-filed specification at the time of the invention. Applicants are referred to the rejection set forth in this Office Action which addresses these issues.
6) The rejection of claims 1-4, 13, 15, 16, 19 and 20 set forth in paragraph 13 of the Office Action mailed 02/19/26 under 35 U.S.C § 103 as being unpatentable over Nelson et al. (US 20020058027 A1, of record) (‘027) in view of Nelson et al. (PNAS 103: 10765-10770, 2006, of record) (Nelson et al., 2006) is withdrawn in light of the claim amendments. Most of Applicants’ arguments still relevant are a repetition of those presented previously, which have already been previously addressed by the Office. A new/modified rejection is set forth in this Office Action to address the claims as amended.
Applicants submit that there is no aspect of Nelson 2002's disclosure, nor Nelson
2002's disclosure as modified by Nelson 2006 and/or Liu, which would have rendered the
presently claimed enzymatic extraction agent obvious without the benefit of hindsight, using the
instant claims as a template. The Office disagrees and directs Applicants to the art rejection set forth in this Office Action. Further, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Applicants argue that neither reference mentions or suggests an extraction agent containing both the claimed (i) a recombinant PlyC comprising a PlyCA gene product and a PlyCB gene product, and (ii) a labeled antibody that specifically binds to a Group A Streptococcus-specific antigen and none recites a dual-component extraction agent. In response, Applicants are reminded that the references of Nelson et al. (‘027) and Nelson et al. (2006) are not used by the Office as anticipatory references. The 103 art rejection set forth in this Office Action clearly documents that the prior art disclosure teaches what Applicants allege are not being taught. For instance, particularly, lines 12-24 of right column on page 14 of Nelson et al. (‘027) within section [0150] expressly taught a product comprising a labeled Group A Streptococcal Antibody suspended in a buffer to which was added the homogeneously purified C1 bacteriophage lysin enzyme (i.e., PlyC), mixed, filtered, aliquoted and lyophilized. Thus, in one embodiment, Nelson et al. (‘027) expressly taught a lyophilized (dried) product that comprised both of components (i) and (ii) of the instantly claimed product.
7) The rejection of claim 17 set forth in paragraph 15 of the Office Action mailed 02/19/26 under 35 U.S.C § 103 as being unpatentable over Nelson et al. (US 20020058027 A1, of record) (‘027) as modified by Nelson et al. (PNAS 103: 10765-10770, 2006, of record) (Nelson et al., 2006) is as applied to claim 1 above and further in view of Liu et al. (US 20110097723 A1, of record) is withdrawn in light of the withdrawal of the rejection of the base claim 1 supra. A new/modified rejection is set forth in this Office Action to address.
8) The rejection of claim 18 set forth in paragraph 14 of the Office Action mailed 02/19/26 under 35 U.S.C § 103 as being unpatentable over Nelson et al. (US 20020058027 A1, of record) (‘027) as modified by Nelson et al. (PNAS 103: 10765-10770, 2006, of record) (Nelson et al., 2006) is as applied to claim 1 above is withdrawn in light of the withdrawal of the rejection of the base claim 1 supra. A new/modified rejection is set forth in this Office Action to address.
Rejection under 35 U.S.C § 112(a) or (Pre-AIA ) First Paragraph
9) The following is a quotation of 35 U.S.C § 112(a):
(a) IN GENERAL. The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C § 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out the invention.
10) Claims 1-4, 11, 13 and 15-20 are rejected under 35 U.S.C § 112(a) or 35 U.S.C § 112 (pre-AIA ), first paragraph, as containing subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The purpose of the written description requirement is ‘to ensure that the inventor had possession, as of the filing date of the application relied on, of the specific subject matter later claimed by him.’ In re Edwards, 568 F.2d 1349, 1351-52, 196 USPQ 465, 467 (CCPA 1978). The analysis of whether the as-filed specification complies with the written description requirements calls for the Office to compare the scope of the claims with the scope of the description to determine whether Applicants have demonstrated possession of the full scope of the claimed invention at the time of the invention. In the instant application, an analysis of the scope of the claims and of the variant genus encompassed therein indicates the following.
In the instant case, the base claim 1 is representative of the claimed invention. It is drawn to an enzymatic extraction agent in the form of a lyophilized or dried composition comprising a recombinant PlyC comprising a PlyCA gene product and a PlyCB gene product and a labeled antibody that specifically binds to a Group A Streptococcus-specific antigen. Independent claims 19 and 20 include a similar enzymatic extraction agent comprising a recombinant PlyC. Paragraph [0097] of Applicants’ as-filed specification defines “PlyC” as the “streptococcal C1 bacteriophage lysin”, a peptidoglycan hydrolase enzyme, i.e., a protein. Paragraph [0058] of Applicants’ as-filed specification states that the terms “protein”, “polypeptide”. “oligopeptide” and “peptide” are used interchangeably. Therefore, the claimed ‘PlyC’, ‘a PlyCA gene product’, and ‘a PlyCB gene product’ encompass full-length protein or full-length polypeptide species as well as oligopeptide and peptide species of unlimited structure. PlyC encompasses PlyC comprising PlyCA and PlyCB derivatives, and recombinant PlyCA mutant and recombinant PlyCB mutant as set forth in the original claims 11-13, 9, 10 and 1. Sections [0105] and [0016] of the as-filed specification exemplify a mutant PlyC, a recombinant PlyC, a recombinant PlyCA mutant, and a recombinant PlyCB mutant as a ‘derivative’ of PlyC. Thus, the claim term ‘a recombinant PlyC’ in instant claims encompasses a PlyC that comprises PlyCA and PlyCB derivative species and mutant species, which include those having a sequence that is greater than 70% sequence identity or homology to PlyC. See section [0063] of the as-filed specification. Accordingly, the term “PlyC” represents a huge genus of structurally divergent species of variable length/size. The PlyC recited in claim 1 or in claims 19 and 20 is not identified by its precise sequence or the SEQ ID number such that one could envision the structure of 70% identical or homologous PlyC derivative species, or the PlyC oligopeptide species of unlimited structure and size/length, each having the requisite extraction function. The recombinant PlyC as claimed is not an inert component, instead an essential component of the claimed product that is required for the extracting function in the claimed enzymatic extraction agent. The PlyCA gene product and PlyCB gene product are not ‘mere’ components of the claimed product, but are a part of the recited PlyC element that is required and necessary for the claimed product to work for the intended purpose. As known to skilled artisans, said derivative species would include amino acid deletions, insertions, substitutions and/or other modifications within the PlyCA and/or PlyCB such that the derivative species are up to 30% non-identical or non-homologous to the native PlyC. Such oligopeptide, mutant and derivative PlyC species are required to function as an ‘enzymatic’ extraction agent in the instantly claimed products and are to be used for ‘extraction’ of a biological sample which will be used as an antigen source in an immunoassay such as the Strep A lateral flow test strip for detecting the presence or absence of Group A Streptococcus. See section [0105] and claim 19 of the as-filed specification. Thus, the ‘mutants’ which are referred to as derivatives of the PlyCA and PlyCB components of the recombinant PlyC are of any unspecified structure and size/length or those having up to 30% non-identity or non-homology to the PlyC holoenzyme. These represent a large genus encompassing structurally variable PlyCA and PlyCB derivative species and structurally variable PlyCA and PlyCB oligopeptide species, each with the requisite enzymatic extraction function. However, Applicants were not in possession of the variant genus and the full scope of the claimed invention at the time the application was filed.
The written description requirement can be met by describing the claimed subject matter to a person skilled in the art using sufficiently detailed, relevant identifying characteristics such as functional characteristics, and correlating those functional characteristics with a disclosed structure. See Enzo Biochem v. Gen-Probe, 323 F.3d 956, 964, 967, 968 (Fed. Cir. 2002). Sufficient description to show possession of a genus may be achieved by means of disclosure of a representative number of species, defined by structure falling within the scope of the genus, or recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. MPEP § 2163.02 states, ‘[a]n objective standard for determining compliance with the written description requirement is, ‘does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed’. The courts have decided [Emphasis added]:
The purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for the purposes of the “written description” inquiry, whatever is now claimed.
See Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Note that the written description provision of 35 U.S.C § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In the instant case, the precise structure of the highly variable recombinant PlyC species that comprise PlyCA and PlyCB gene products, each encompassing variable PlyCA derivative or mutant species and PlyCB derivative or mutant species within the claimed broad genus is not correlated with the requisite enzymatic extraction function such that a test sample extracted with said structurally divergent species serves as an effective antigen source for an immunoassay such as the Strep A lateral flow test strip and detects the presence or absence of Group A Streptococcus in a test sample. A representative number and variety of PlyC species encompassing structurally variable homologs up to 30% non-identical or non-homologous to the unmodified or native PlyCA- and PlyCB-containing PlyC, each correlated with the ability to be utilized as an enzymatic extraction agent was not in Applicants’ possession at the time of the invention. A convincing structure-function relationship must exist between the structure of a representative number and variety of the various species encompassed within the broad variant genus and within the scope of the claims and their requisite function. This is important because the purpose of the instant invention is to use the encompassed PlyC species as enzymatic extraction agents. Although one of skill can make amino acid substitutions, additions, deletions, modifications and/or insertions in the native PlyC holoenzyme, there is no predictability that such variant PlyC species would retain the requisite enzymatic extraction function. Applicants have provided no evidence showing that said structurally highly diverse species having the requisite extraction function existed in the field or in scientific literature at the time of the invention. The state of the art at the time of the invention disclosed that assigning functional activities for any particular protein or a family of proteins based upon sequence homology is inaccurate, partly because of the multifunctional nature of proteins. See abstract; and page 34 of Skolnick et al. Trends in Biotechnology 18: 34-39, 2000 (of record). Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan’s best guess as to the function of the structurally related protein. See abstract and Box 2 of Skolnick et al. With regard to the structure-function relationship of an encoded amino acid sequence in general, Rudinger J. In: Peptide Hormones. (Ed) JA Parsons, University Park Press, pages 1-7, 1976 (of record) taught that ‘the significance of particular amino acid sequences for different aspects of biological activity cannot be predicted a priori but must be determined from case to case by painstaking experimental study’. See page 6 of Rudinger J. Rudinger J further taught that ‘it is impossible to attach a unique significance to any residue in a sequence’ and that a ‘given amino acid will not by any means have the same significance in different peptide sequences, or even in different positions of the same sequence. See page 3 of Rudinger J. Without a concrete structure-function correlation, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. Ex parte Kubin, 83 USPQ2d 1410 (Bd. Pat. Appl. & Int. 2007) citing Eli Lilly, 119 F.3d at 1568, 43 USPQ at 1406 (‘definition by function ….. does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is’). At the time of the invention, one could not have predicted the enzymatic extraction function of the up to 30% non-identical or non-homologous species encompassed within the scope of the recited PlyC.
Again, based on Applicants’ express definition and description within their as-filed specification, the recited PlyC encompasses within its scope, members and derivatives that are up to 30% non-identical or non-homologous to the PlyC comprising a PlyCA gene product and a PlyCB gene product. The various species encompassed within the claimed genus are structurally divergent. Said highly structurally variable members within the genus are required to function as an enzymatic extraction agent in the instantly claimed products and are to be used for extraction of a biological sample which will be used as an antigen source in an immunoassay such as the Strep A lateral flow test strip for detecting the presence or absence of Group A Streptococcus. See section [0105] and claim 19. However, no convincing structure-function correlation exists for a representative number and variety of such members encompassed within the scope of the genus. This is important because the purpose of the instant invention is to use the claimed PlyC mutant derivatives as enzymatic extraction agents. The as-filed specification defines “PlyC” as the “streptococcal C1 bacteriophage lysin”, a peptidoglycan hydrolase enzyme. Particularly with regard to enzymatic bacterial polypeptides, the art recognizes that even the existence of as high as at least 95%, or even 98% sequence identity between two enzymatic bacterial polypeptides is not necessarily predictive of identical or near identical functional activity. For example, the state of the art documents that two enzymatic bacterial polypeptides which are 98% identical to each other can be functionally different. See title; abstract; and the last sentence of paragraph bridging pages 2405 and 2406 of Seffernick et al. (J. Bacteriol. 183: 2405-2410, 2001, of record). Even with conservative amino acid substitutions within a protein, the state of the art documents functional unpredictability. For example, Lazar et al. (Mol. Cellular Biol. 8: 1247-1252, 1988, of record) demonstrated that a substitution of the Leu residue with a conservative amino acid residue such as, Ile or His, in the transforming growth factor (TGF) alpha led to a mutant protein with dramatically altered biological activities. Lazar et al. stated that they ‘did not expect that a mutation of Leu to Ile (which have similar sizes and polarities) would cause such a strong effect’. See paragraph bridging left and right columns on page 1251; and third full paragraph on page 1251. The art in general reflects unpredictability as to which amino acids in a specific protein or a polypeptide sequence can be varied or mutated without adversely affecting the functional properties of that specific protein or polypeptide sequence. While it is known in the art that variation, mutation and/or deletion of one or more amino acids is possible in a given protein or sequence, the exact position within its amino acid sequence where replacements, mutations or variations can be made, with a reasonable expectation of success of retaining the sequence’s functional competence, is not certain or predictable. A random replacement affecting the amino acid positions that are critical, for example, to the three-dimensional conformational structure and specific functional property of the protein or polypeptide, would result in a protein or polypeptide that may be non-functional, or not optimally functional, because such positions tolerate no or little modifications. For instance, Mikayama et al. (Proc. NatI. Acad. Sci. USA, 90: 10056-10060, 1993. Of record) taught that the three-dimensional structure of molecules is important for their biological function and even a single amino acid difference may account for markedly different biological activities. In the instant case, the capacity of the structurally variable PlyC species as defined and described by Applicants within their as-filed specification and as encompassed within the broad genus to retain the functions of the unmodified native PlyC holoenzyme was neither predictable, nor was it established within the instant application at the time of the invention. Even if one produced up to 30% non-identical variants of the PlyC falling within the scope of the instant claims, there is no predictability that such structurally variable variant species would have the requisite enzymatic extraction function. Clearly, a convincing structure-function correlation for the entire variable genus is lacking. The Office notes that Applicants have advanced no arguments with regard to the cited references of Skolnick et al. Trends in Biotechnology 18: 34-39, 2000 (of record), Rudinger J. (In: Peptide Hormones. (Ed) JA Parsons, University Park Press, pages 1-7, 1976, of record), Seffernick et al. (J. Bacteriol. 183: 2405-2410, 2001), Lazar et al (Mol. Cellular Biol. 8: 1247-1252, 1988), and Mikayama et al. (Proc. NatI. Acad. Sci. USA, 90: 10056-10060, 1993), the teachings of which are used to establish the issue of art-recognized unpredictability in the absence of a showing possession within the as-filed specification.
Adequate written description of a genus embracing unknown species or widely variant species cannot be achieved by disclosure of one species within the genus. ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when .… the evidence indicates that ordinary artisans could not predict the operability in the invention of any species other than the one disclosed’. In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004). See MPEP 2163 IBII.A. The instant specification does not describe sufficient members of the claimed vast genus by complete structure along with a convincing correlation to the requisite function. One of skill in the art would not reasonably conclude that the disclosure provides a representative number and variety of species to describe the genus. Applicants have not described the genus of encompassed recombinant PlyC species including the encompassed derivative species such that the specification might reasonably convey to the skilled artisan that Applicants had possession of the claimed invention at the time the application was filed. In the instant case, Applicants’ specification does not contain a written description sufficient to show they had possession of a sufficient number and variety of species within the variant genus and the full scope of the claimed invention at the time the application was filed. Instant claims do not meet the written description requirement.
Claim(s) Interpretation
11) The claim limitation ‘PlyC’ is interpreted as per the definition and description in Applicants’ as-filed specification and in accordance with the definition and description already disclosed in the prior art. The claimed “PlyC” is recognized in the art as the “streptococcal C1 bacteriophage lysin”, a unique lysin composed of two gene products, PlyCA and PlyCB, a multimeric bacteriophage cell-wall hydrolase. The art taught that ‘PlyC’ stands for “phage lysin from C1”, which was first described in 1957. See title; and left column of page 10765 including the 1st two lines of the last partial paragraph therein of Nelson et al. (PNAS 103: 10765-10770, 2006, of record) (hereinafter Nelson et al., 2006). Nelson et al. (2006) identified said ‘PlyC’ as a multimeric ‘holoenzyme’. See the 2nd and 3rd full sentences under ‘Conclusions’ on page 10768 of Nelson et al. (2006).
It is important to note that consistent with the disclosure of Nelson et al. (2006) set forth supra, Applicants’ as-filed specification at paragraph [0097] also defines the claimed “PlyC” as the “streptococcal C1 bacteriophage lysin”, a most potent peptidoglycan hydrolase enzyme that is multimeric lysin composed of PlyCA and PlyCB gene products. The PlyC recited in instant claims is not identified by its precise sequence or the SEQ ID number. Paragraph [0058] of Applicants’ as-filed specification states that the terms “protein”, “polypeptide”, “oligopeptide” and “peptide” are used interchangeably.
Furthermore, PlyC encompasses PlyC comprising PlyCA and PlyCB derivatives, and recombinant PlyCA mutant and recombinant PlyCB mutant as set forth in the original claims 11-13, 9, 10 and 1. Sections [0105] and [0016] of the as-filed specification exemplify a mutant PlyC, a recombinant PlyC, a recombinant PlyCA mutant, and a recombinant PlyCB mutant as a ‘derivative’ of PlyC. Thus, the claim term ‘a recombinant PlyC’ in instant claims encompasses a PlyC that comprises PlyCA and PlyCB derivative species and mutant species, which include those having a sequence that is greater than 70% sequence identity or homology to PlyC, i.e., up to 30% non-identity or non-homology. See section [0063] of the as-filed specification. Therefore, the claimed ‘PlyC’, ‘a PlyCA gene product’, and ‘a PlyCB gene product’ encompass full-length native protein or full-length native polypeptide species as well as less than full-length native protein or less than full-length native polypeptide species, structurally modified mutant species, structurally modified derivative species, and oligopeptide and peptide species of unlimited structure and size/length.
No claims recite a SEQ ID number and therefore a specific SEQ ID number is not a claim limitation to be met. The claim limitation “recombinant” in claims 1, 19 and 20, represents a product-by-process limitation. The 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 over 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). Therefore, references which teach or make obvious the product claimed in the claims will be applied for prior art purposes under 35 U.S.C. § 102 and/or 103.
The instantly claimed agent is disclosed in the as-filed specification as existing in a lyophilized or dried form prior to its rehydration or reconstitution with a liquid, similar to one of the embodiments that is disclosed by the applied prior art.
Rejection(s) under 35 U.S.C § 103
12) 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 of this title, 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 claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 148 USPQ 459, that are applied 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 unobviousness.
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 at the time any inventions covered therein were effectively filed absent any evidence to the contrary. Applicants are 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 at the time a later invention was effectively filed 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.
13) Claims 1-4, 13, 15, 16, 19 and 20 are rejected under 35 U.S.C § 103 as being unpatentable over Nelson et al. (US 20020058027 A1, of record) (‘027) in view of Nelson et al. (PNAS 103: 10765-10770, 2006, of record) (Nelson et al., 2006).
Nelson et al. (‘027) disclosed a homogeneously purified C1 bacteriophage lysin protein, a.k.a. ‘PlyC’ as expressly described in Applicants’ as-filed specification. For example, see claim 1 Nelson et al. (‘027) set forth below:
PNG
media_image1.png
43
443
media_image1.png
Greyscale
It was recombinantly produced. Nelson’s (‘027) recombinant C1 bacteriophage lysin has the lytic specificity to the cell walls of group A streptococci. See sections [0024], [0010], and [0038]. Said homogeneously prepared C1 bacteriophage lysin is maintained in ezymatically active form. See section [0066]. Nelson’s (‘027) claims 33 and 32 and section [0014] taught an extraction reagent comprising a lytic amount of said homogeneously purified C1 bacteriophage lysin enzyme of claim 1 for releasing group A streptococcal antigen. Said homogeneously purified C1 bacteriophage lysin enzyme of claim 1 was used in a method of degrading cell walls of group A streptococci, the method comprising contacting the group A streptococci with the homogeneously purified C1 bacteriophage lysin enzyme of claim 1. See Nelson’s (‘027) claims 25 and 24. A lyophilized (dried) composition containing said purified C1 bacteriophage lysin enzyme (PlyC), a salt, and an indicator or chromophore labelled antibody reagent such as a colloidal gold sol labelled antibody specific for a group A streptococcal antigen such as a carbohydrate or cell wall antigen is taught. The antibody was labelled with an indicator particle. The antibody reacts with the antigen released from a swab containing a biological sample specimen containing therein group A streptococci, the swab having been previously treated with the lysin enzyme extraction reagent for less than 6 or 30 minutes. See section [0069] including the last three sentences; and sections [0149] and [0150]. Particularly, lines 12-24 of right column on page 14 of Nelson et al. (‘027) within section [0151] expressly taught a product comprising colloidal gold sol of labeled Group A Streptococcal Antibody suspended in a buffer to which was added the homogeneously purified C1 bacteriophage lysin enzyme (i.e., PlyC), mixed, filtered, aliquoted and lyophilized. Thus, in one embodiment, Nelson et al. (‘027) expressly taught a lyophilized (dried) product that comprised both of components (i) and (ii) of the instantly claimed product. In one embodiment, the antibody is bound (coupled) to latex particles, i.e., microbeads, for purposes of detection of group A strep antigen using any immune detection system including immunofluorescence or a chromophore labelled membrane spot test. See sections [0153], [0154] and [0152]. A plastic laminate device comprising a cellulose acetate filter matrix situated thereon with a swab from an area infected with Group A streptococcus or a swab seeded with Group A streptococcus after being treated with the extraction reagent containing the C1 bacteriophage lysin enzyme, i.e., the a.k.a. ‘PlyC’, and the chromophore-labelled antibody placed thereon (the sample receiving zone) is taught, wherein the device further comprised two holes apart from each other, one containing a detection membrane (capture zone) that is saturated with a rabbit anti-streptococcal group A capture antibody. If the Group A streptococcus antigen is present in the swab containing the infected sample, an immune complex is deposited and captured on the detection membrane (capture zone) resulting in a color that is visualized on the detection membrane. See sections [0150] and [069]. A diagnostic test kit for the accurate and rapid detection of group A streptococci in biological samples comprising said immunoassay device, said enzyme reagent, and instructions for use is taught. See sections [0066], [0069] and [0155].
Nelson et al. (‘027) appears to be silent on a PlyCA gene product and a PlyCB gene product being comprised in their homogeneous purified C1 bacteriophage lysin protein, a.k.a. ‘PlyC’.
However, a recombinant multimeric PlyC comprising PlyCA and PlyCB gene products having the lytic activity was known in the art at the time of the invention. For instance, along with the description similar to the description in Applicants’ as-filed specification, Nelson et al. (2006) identified the “PlyC” as the “streptococcal C1 bacteriophage lysin” or the “phage lysin from C1” holoenzyme, a unique lysin composed of two gene products, PlyCA and PlyCB, a multimeric bacteriophage cell-wall hydrolase. See title; left column of page 10765 including the 1st two lines of the last partial paragraph therein; and the 2nd and 3rd full sentences under ‘Conclusions’ on page 10768 of Nelson et al. (2006). Nelson et al. (2006) taught the recombinantly produced and purified PlyC holoenzyme comprising both PlyCA and PlyCB gene products. Nelson et al. (2006) demonstrated via experiments that the minimal region necessary for the “lytic activity”, i.e., “the group A streptococcal cell wall-lytic activity”, is the multimeric full-length PlyC, which is composed of PlyCA and PlyCB subunits. Nelson et al. (2006) showed that a recombinant expression construct that contained full-length plyCB and plyCA regions, did encode lytic activity. See at least page 10766, right column in particular; Figure 1 description; 2nd and 4th full paragraphs in right column of page 10766; section ‘Results and Discussion’; 2nd and 3rd full sentences under ‘Conclusions’ on page 10768; and the paragraph bridging pages 10766 and 10767.
Given the express teachings of Nelson et al. (2006), it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of instant application to have Nelson’s (2006) recombinant, multimeric PlyC holoenzyme comprising the two gene products, PlyCA and PlyCB, and having the group A streptococcal cell wall-lytic activity in place of Nelson’s (‘027) streptococcal C1 bacteriophage lysin, a.k.a PlyC, to produce the instant invention. Substitution of one art-known recombinant streptococcal C1 bacteriophage lysin, a.k.a PlyC, having the group A streptococcal cell wall-lytic or -degrading activity with another, art-known, functionally equivalent streptococcal C1 bacteriophage lysin, a.k.a PlyC full-length holoenzyme comprising the PlyCA and PlyCB subunits that was already demonstrated in the art as having the group A streptococcal cell wall-lytic activity would have been well within the realm of routine experimentation, would have been obvious, and would have yielded similar predictable results. Substitution of one element for another known equivalent in the field is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See KSR International Co. v Teleflex Inc. 82 USPQ2d 1385 (US 2007) at page 1395. To those of ordinary skill in an art, it is generally obvious to replace a known product by substituting a known equivalent for one of its components. See e.g., Hotchkiss v. Greenwood, 52 U.S. 248 (1850) (substitution of porcelain door knob in known process of making metal or wood door knobs held obvious); In re Mayne, 104 F.3d 1339, 1340 (Fed. Cir. 1997) ("Because the applicants merely substituted one element known in the art for a known equivalent, this court affirms [the rejection for obviousness])." As set forth in KSR Int'l Co. v. Teleflex Inc., 27 S. Ct. 1727, 1741-42, 82 USPQ2d 1385, 1397 (2007), [i]n determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. What matters is the objective reach of the claim. If the claim extends to what is obvious, it is invalid under § 103"; see also In re Beattie, 974 F.2d 1309, 1312, 24 USPQ2d 1040, 1042 (Fed. Cir. 1992) ("[T]he law does not require that the references be combined for the reasons contemplated by the inventor."). The test of obviousness is not express suggestion of the claimed invention in any and all of the references, but rather what the references taken collectively would reasonably have suggested to those of ordinary skill in the art presumed to be familiar with them. In re Keller, 642 F.2d 413, 425, 208 USPQ 871, 881 (CCPA 1981). Obviousness does not require absolute predictability (see In re Lamberti, 192 USPQ 278), but only a reasonable expectation of success (see In re O’Farrell, 7 USPQ 2d 1673, Fed. Cir. 1988).
Claims 1-4, 13, 15, 16, 19 and 20 are prima facie obvious over the prior art of record.
14) Claim 18 is rejected under 35 U.S.C § 103 as being unpatentable over Nelson et al. (US 20020058027 A1, of record) (‘027) as modified by Nelson et al. (PNAS 103: 10765-10770, 2006, of record) (Nelson et al., 2006) as applied to amended claim 1 above.
The teachings of Nelson et al. (‘027) as modified by Nelson et al. (2006) are set forth above, which are silent on the lytic amount, i.e., concentration, of their homogeneously purified, recombinant, enzymatically active C1 phage lysin protein that lyses group A streptococci and releases group A streptococcal (Strep A) antigen to be in the broadly recited range of from 0.1 to 80 micrograms/mL.
However, MPEP 2144.05 states that generally, differences in concentration or amount
will not support the patentability of subject matter encompassed by the prior art unless there is
evidence indicating such concentration is critical. In re Hoeschele, 406 F.2d 1403, 160 USPQ
809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the
references were held to be unpatentable thereover because, among other reasons, there was
no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). It
has been held legally obvious and within the routine skill in the art to optimize a result-effective
variable. In the instant case, it is the Office’s position that there is no evidence of criticality of the
recited broad concentration range and thus there is motivation for one of ordinary skill to arrive
at a concentration falling within the broadly recited range via routine optimization.
Claim 18 is prima facie obvious over the prior art of record.
15) Claim 17 is rejected under 35 U.S.C § 103 as being unpatentable over Nelson et al. (US 20020058027 A1, of record) (‘027) as modified by Nelson et al. (PNAS 103: 10765-10770, 2006, of record) (Nelson et al., 2006) as applied to amended claim 1 above and further in view of Liu et al. (US 20110097723 A1, of record).
The teachings of Nelson et al. (‘027) as modified by Nelson et al. (2006) are set forth supra, which are silent on their antibody-coupled microbeads colored or dyed with europium chelate compound.
However, having such beads dyed or colored with fluorescent europium chelate compound for convenient detection purposes was routine and very conventional in the art at the time of the invention. For example, see sections [0069] and [0063] of Liu et al.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use alternate, art-known beads such as fluorescent europium dyed microbeads in place of fluorescent-labeled beads in Nelson’s (‘027) product as modified by Nelson et al. (2006) to produce the instant invention. Substitution of one fluorescent-labeled beads with another, alternate, art-known beads such as fluorescent europium dyed microbeads for the same detection purpose would have been well within the realm of routine experimentation, would have been obvious to one of ordinary skill in the art, and would have resulted in similar predictable effects or results. Substitution of one element for another known in the field is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See KSR International Co. v Teleflex Inc. 82 USPQ2d 1385 (US 2007) at page 1395. To those of ordinary skill in an art, it is generally obvious to replace a known product by substituting a known equivalent for one of its components. See e.g., Hotchkiss v. Greenwood, 52 U.S. 248 (1850) (substitution of porcelain door knob in known process of making metal or wood door knobs held obvious); In re Mayne, 104 F.3d 1339, 1340 (Fed. Cir. 1997) ("Because the applicants merely substituted one element known in the art for a known equivalent, this court affirms [the rejection for obviousness]." As set forth in KSR Int'l Co. v. Teleflex Inc., 27 S. Ct. 1727, 1741-42, 82 USPQ2d 1385, 1397 (2007), [i]n determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. What matters is the objective reach of the claim. If the claim extends to what is obvious, it is invalid under § 103"; see also In re Beattie, 974 F.2d 1309, 1312, 24 USPQ2d 1040, 1042 (Fed. Cir. 1992) ("[T]he law does not require that the references be combined for the reasons contemplated by the inventor."). In KSR Int’l v. Teleflex Inc., the Supreme Court indicated that ‘[w]hen a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, 103 likely bars its patentability.’ KSR Int’l v. Teleflex Inc., 127 S. Ct. at 1727, 1740 (2007). As set forth in KSR Int'l Co. v. Teleflex Inc., 27 S. Ct. 1727, 1741-42, 82 USPQ2d 1385, 1397 (2007), ‘[i]n determining whether the subject matter of a patent claim is obvious, neither the particular motivation nor the avowed purpose of the patentee controls. If the claim extends to what is obvious, it is invalid under § 103’.
Claim 17 is prima facie obvious over the prior art of record.
Conclusion
16) No claims are allowed.
17) Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. THIS ACTION IS MADE FINAL. Applicants are reminded of the extension of time policy as set forth in 37 C.F.R 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 extension fee pursuant to 37 C.F.R 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.
Correspondence
18) Any inquiry concerning this communication or earlier communications from the Examiner should be directed to S. Devi, Ph.D., whose telephone number is (571) 272-0854. A message may be left on the Examiner’s voice mail system. The Examiner is on a flexible work schedule, however she can normally be reached Monday to Friday from 8.00 a.m. to 4.00 p.m. (EST). If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s Supervisor, Jeffrey Stucker, can be reached at (571) 272-0911. The fax phone number for the organization where this application or proceeding is assigned (571) 273-8300.
19) Information regarding the status of an application may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center or Private PAIR to authorized users only. Should you have questions about access to Patent Center or the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). 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.
/S. DEVI/
S. Devi, Ph.D.Primary Examiner
Art Unit 1645
August, 2026
Prosecution Insights