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.
Status of Claims
Claims 1-9, 11, 13-18 and 20-22 are pending. Claims 11, 13-15, 18 and 20-22 are withdrawn. Claims 1-9, 16-17 and 19 are under examination.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-9, 16-17 and 19) in the reply filed on 03/20/2026 is acknowledged. Further, Applicant has elected the species of formula V. In view of the search and compact prosecution, the elected species are hereby withdrawn. Claims 1-9, 16-17 and 19 are under examination.
Claims 11, 13-15, 18 and 20-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-9, 16-17 and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
With respect to claim 1, a broad limitation together with a narrow limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitation “a complex comprising a linker, wherein the linker covalently binds a label compound and an analyte-specific binding agent”, and the claim also recites “the complex is a compound of formula I:….” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Additionally, the claim does not recite a connection between the linker recited in (b) and […]n of formula I.
With respect to claims 1 and 7-8, claim 1 recites that the complex is a compound that requires an analyte-specific binding agent and claims 7-8 recite complexes of formula IV-1, V and VI, but these complexes do not have the analyte-specific binding agent. In particular, a maleimide group would not be considered an analyte-specific binding agent. Thus, claim 1 is unclear to what is being directly attached to […]n of formula I and whether the analyte-specific binding agent is present in formula (I). Thus, the claim is unclear to the structure of an “analyte-specific binding agent”. Claims 2-6, 9, 16-17 and 19 are rejected as being dependent from claim 1.
Claim 6 recites that the label compound is covalently bonded to the linker by the recited first conjugation method which contains a plurality of different linkages. The claim is unclear to whether these first conjugation linkages are directed to the general linker or formula I because, for example, zide-alkyne formation of a click chemistry method does not even appear to partially reflect the chemical structures in […]n of formula I.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 7 and 8 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 1 recites that the complex of formula I requires the analyte-specific binding agent, but claims 7-8 recite complexes that do not contain an analyte-specific binding agent. Additionally, claim 1 recites in the formula I that the analyte-specific binding agent is a direct covalent attachment to […]n of formula I, but claims 7-8 requires additional maleimide spacer to conjugate the analyte-specific binding agent. Thus, these claims are broadening the scope of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1, 3-4, 6, 9, 16-17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Josel et al. (US20180364175A1, published 12/20/2018) in view of Huang et al. (US20170065726A1, published 03/09/2017).
With respect to claims 1 and 3-4, Josel teaches new reagent compositions for measuring electrochemiluminescence (ECL) (abstract). Josel further teaches detecting the ECL signal comprising contacting a reaction composition comprising at least one branched-chain tertiary amine and an ECL compound comprising a transition metal complex with an electrode, electrochemically triggering the release of luminescence and detecting the ECL signal wherein the method detecting an analyte in a sample via electrochemiluminescence detection (see paras. [0008]-[0019]). Josel further teaches the compound is biotin0DADOO-sulfo-BPRu of formula (VIII) (see structure below).
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(see para. [0282]).
Although the Josel teaches a label compound (Ru2+), analyte-specific binding agent (biotin), and a PEG linker, the reference does not teach the linker of formula (I).
Huang teaches a sugar alcohol-based molecules can have functional groups throughout the molecule for crosslinking compounds (see abstract). Fig. 1 shows that the chemical structures of SA linker and PEG linker. Huang further teaches that SAs have better hydrophilicity and higher hydrodynamic volume than polyethylene glycol (PEG) and SAs can be derivatized and modified to allow for the incorporation of various functional groups and activation groups to produce SA crosslinking reagents (see paras. [0003]-[0004]). Fig. 9 shows the structure of amie bond linked SA molecule containing an amide group and carbonyl group wherein X is OH, m is an integer from 1 to 8, n is 4, r and s are 0, and z is an integer > 1. Huang teaches biotin, a fluorescent compound, and chemiluminescent compound may be linked to B (i.e., SA) (see para. [0027]). Huang teaches configuration of hyperbranched SA macromolecule (see Fig. 10). Huang teaches that symmetrically branched, asymmetrically branched and linear of SA molecules (see Fig. 11).
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 modified the compound as taught by Josel with the sugar alcohol-based(SA) molecules as taught by Huang because Huang teaches that the sugar alcohol-based (SA) linker has a better hydrophilicity and higher hydrodynamic volume than the polyethylene glycol (PEG) linker, and SA linkers can be derivatized and modified to allow for the incorporation of various functional and activation groups.
Meanwhile, the person would have a reasonable expectation of success in replacing PEG with SA molecules in Josel’s compound because it has been well understood by Huang that PEG and SA are spacers and linkers that are conjugating chemiluminescent compounds and biotin.
With respect to claim 6, Josel teaches in formula (VIII) amide conjugation and labeled antibody (see para. [0068], right col.).
With respect to claims 9 and 17, the claims are directed to a method of detecting with the product of the compound of formula (I). As stated above, the combination of said references reads on the compound of formula (I) as recited in claim 1. Thus, the phrases “a peptide-based synthesis” and “solid phase peptide synthesis” are product-by-process limitations.
As noted above, “[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. (Emphasis added).
With respect to claim 16, Josel teaches electrochemiluminescence detection (see paras. [0008]-[0019]).
With respect to claim 19, Huang teaches in Fig. 9 the amide bond linked SA molecule wherein n is 2. With respected with the claimed formula (I), Huang does teach n is 4 but does not teach the claimed n is 5 and r and s are 0. Meanwhile, homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.). (see MPEP 2144.09 (II)). Additionally, the court also held that although the prior art compounds were not true homologs or isomers of the claimed compounds, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new pesticides.). (see MPEP 2144.09 (II). Thus, the person would have been motivated to make the claimed compounds with n is 5 and r and s are 0 in search for new SA spacers.
Claims 1-9, 16-17 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Andres et al. (WO0227315A2, published 04/04/2002) in view of Huang et al. (US20170065726A1, published 03/09/2017).
With respect to claims 1-5, Andres teaches new compounds comprising a branched linker and their use for producing conjugates for application in diagnostic or therapeutic methods (see abstract). Andres teaches a metal complex is used as the labeling group detected by electrochemiluminescence in which luminescent species are generated electrochemical on the surface of an electrode and the electrochemiluminescence assays are carried out in the presence of a solid phase (see pg. 12, lines 8-15). Andres teaches a sample liquid was incubated with a ruthenium-labeled antigen and a biotinylated antigen for the antibody to be determined in the presence of a streptavidin-coated solid phase and the presence of anti-HIV antibodies in the sample liquid is determined by measuring the label on the solid phase means of electrochemiluminescence (see Example 4, pg. 18). Figure. 9 shows ruthenium compound and maleimide compounds conjugated by an amide linker. Figure 9 also shows the presence of OH groups on the amide linker (reproduced below). Andres also teaches Figure 20 an amide linker covalently conjugated to a ruthenium compound and gp36 molecule (reproduced below).
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Andres teaches the synthesis of a charged and branched linker on a labeling group on solid phase binding group can be carried out as a coupling reaction in solution by carboxylic acid (see pg. 9, lines 22-27). Andres teaches the linker can also be prepared by solid phase peptide synthesis (see pg. 10, lines 5-10). Andres further teaches investigations have found that the use of hydrophilic or charged linkers results in considerable advantages in test performance (see pg. 2, lines 1-5). Andres teaches the desired linker is synthesized by successively coupling further amino acids and at least one amino acid which contains a charged groups as a side group such as carboxylate group (see pg. 10, lines 7-10).
Although Andres teaches label compound (Ru2+), analyte-specific binding agent, and an amide linker with carboxylic acid side chains, the reference does not teach X is OH or (CHOH)t-CH2OH with t > 1.
Huang teaches a sugar alcohol-based molecules can have functional groups throughout the molecule for crosslinking compounds (see abstract). Fig. 1 shows that the chemical structures of SA linker and PEG linker. Huang further teaches that SAs have better hydrophilicity and higher hydrodynamic volume than polyethylene glycol (PEG) and SAs can be derivatized and modified to allow for the incorporation of various functional groups and activation groups to produce SA crosslinking reagents (see paras. [0003]-[0004]). Fig. 9 shows the structure of amie bond linked SA molecule containing an amide group and carbonyl group wherein X is OH, m is an integer from 1 to 8, n is 4, r and s are 0, and z is an integer > 1. Huang teaches biotin, a fluorescent compound, and chemiluminescent compound may be linked to B (i.e., SA) (see para. [0027]). Huang teaches configuration of hyperbranched SA macromolecule (see Fig. 10). Huang teaches the presence of hydrophilic linker favors the conjugation reaction and preserves the stability of the final product (see para. [0242]). Huang teaches that symmetrically branched, asymmetrically branched and linear of SA molecules (see Fig. 11). Huang teaches a sugar alcohol has the general formula HO-CH2-(CHOH)n-CH2-OH wherein n is 0-12 (see para. [0199]). Huang teaches maleimide group conjugated to the linker (see para. [606]).
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 modified Figure 9 of Andres with the sugar alcohol-based (SA) molecules of Huang because Andres teaches hydrophilic or charged linkers have considerable advantages in test performance and Huang teaches that the amide bond linked SA molecule (see Fig. 9) has a high hydrophilicity and hydrodynamic volume and SA linkers can be derivatized and modified to allow for the incorporation of various functional and activation groups.
With respect to X is (CHOH)tCH2OH, it would have been obvious to have used the compound of Figure 9 of Andres with HO-CH2-(CHOH)n-CH2-OH as branches as taught by Huang because Huang teaches symmetrically branched and asymmetrically branched SA molecules are produced in comparison with linear SA molecules (see Fig. 11). Because Andres teaches branched linkers and Huang teaches that the sugar alcohol-based (SA) linker has a high hydrophilicity and hydrodynamic volume and SA linkers can be derivatized and modified to allow for the incorporation of various functional and activation groups, it would have been obvious to have used HO-CH2-(CHOH)n-CH2-OH as branches for the structure of Figure 9.
The person would have a reasonable expectation of success in using SA molecules as linkers or branches in Figure 9 of Andres because it has been well understood by Andres and Huang to have OH groups on the linker and these linkers conjugate to chemiluminescent compounds and maleimide groups.
With respect to claim 6, Andres teaches a sample liquid was incubated with a ruthenium-labeled antigen and a biotinylated antigen for the antibody to be determined in the presence of a streptavidin-coated solid phase and the presence of anti-HIV antibodies in the sample liquid is determined by measuring the label on the solid phase means of electrochemiluminescence (see Example 4, pg. 18). Figure. 9 shows ruthenium compound and maleimide compounds conjugated by an amide linker.
With respect to claim 7, Andres does not teach X is OH wherein n is more than 1. As stated above, it would have been obvious to the person to have used the sugar alcohol-based (SA) molecules as taught by Huang with Figure 9 of Andres because Andres teaches hydrophilic or charged linkers have considerable advantages in test performance and Huang teaches that the sugar alcohol-based (SA) linker has a high hydrophilicity and hydrodynamic volume and SA linkers can be derivatized and modified to allow for the incorporation of various functional and activation groups.
With respect to claim 8, it would have been obvious to the person to have produced a linear Figure 9 of Andres because Andres teaches similar linear structures are produced in conjugating the ruthenium compound and analyte-specific binding agent (see Figure 20). With respect to formula V (elected species), it would have been obvious to have used the compound of Figure 9 of Andres with HO-CH2-(CHOH)n-CH2-OH as branches of Huang because Huang teaches symmetrically branched and asymmetrically branched SA molecules are produced in comparison with linear SA molecules (see Fig. 11). Because Andres teaches branched linkers and Huang teaches that the sugar alcohol-based (SA) linker has a high hydrophilicity and hydrodynamic volume and SA linkers can be derivatized and modified to allow for the incorporation of various functional and activation groups, it would have been obvious to have used HO-CH2-(CHOH)n-CH2-OH as branches for the structure of Figure 9.
Because Huang teaches the sugar alcohol has the general formula HO-CH2-(CHOH)n-CH2-OH wherein n is 0-12 (see above) and Huang’s formula overlaps with the claimed range wherein X is (CHOH)tCH2OH wherein t is 3 and claimed n is more than 1, a prima facie case of obviousness exists.
With respect to claims 9 and 17, the claims are directed to a method of detecting with the product of the compound of formula (I). Andres teaches the linker can also be prepared by solid phase peptide synthesis (see pg. 10, lines 5-10). Meanwhile, the phrases “a peptide-based synthesis” and “solid phase peptide synthesis” are product-by-process limitations.
As noted above, “[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. (Emphasis added).
With respect to claim 16, Andres teaches a metal complex is used as the labeling group detected by electrochemiluminescence in which luminescent species are generated electrochemical on the surface of an electrode and the electrochemiluminescence assays are carried out in the presence of a solid phase (see pg. 12, lines 8-15).
With respect to claim 19, Huang teaches in Fig. 9 the amide bond linked SA molecule wherein n is 2. With respected with the claimed formula (I), Huang does teach n is 4 but does not teach the claimed n is 5 and r and s are 0. Meanwhile, homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril.). (see MPEP 2144.09 (II)). Additionally, the court also held that although the prior art compounds were not true homologs or isomers of the claimed compounds, the similarity between the chemical structures and properties is sufficiently close that one of ordinary skill in the art would have been motivated to make the claimed compounds in searching for new pesticides.). (see MPEP 2144.09 (II). Thus, the person would have been motivated to make the claimed compounds with n is 5 and r and s are 0 in search for new SA spacers.
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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