Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-3, 6-10, 12-19, 22, 24-27, 30-32, 34-36, and 38-39 are pending in the application and are the subject of this office action.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph 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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 his invention.
Claims 1-3, 7-10, 12-19, 22, 24-27, 30-32, 34-36, and 38-39 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. See MPEP 2163.
The inventions of independent claims 1, 14, and 25 are directed to methods comprising contacting a sample with an antibody or antibody fragment that specifically binds to apo(a), wherein the antibody or antibody fragment may comprise alternative (i) or alternative (ii), wherein antibody or antibody fragment (i) comprises the binding specificity of LPA4 such that the antibody or antibody fragment binds to KIV5, KIV7, and KIV8.
As such, the independent claims encompass a genus of antibodies and antibody fragments which are defined by their binding function.
Dependent claims 2, 9-10, 12-13, 15-19, 22, 31-32, 34-36, and 38-39 further limit different aspects and materials used in the disclosed method, but do not further limit the structure of antibody or antibody fragment (i) itself.
Dependent claim 3 further limits antibody or antibody fragment (i) by indicating that the antibody or antibody fragment comprises light chain and heavy chain CDRs of an LPA4 antibody, but does not define the CDRs, and does not indicate whether the antibody or antibody fragment (i) requires all light chain and heavy chain CDRs of the LPA4 antibody, or whether it only requires some of the CDRs.
Dependent claim 8 further limits the antibody or antibody fragment by stating that it binds to an epitope comprising SEQ ID NO: 17, but does not indicate whether this limitation is relevant to antibody or antibody fragment (i), (ii), or both. It is not clear from the context of the claim whether this limitation is included in or further limits an antibody or antibody fragment comprising the binding specificity of LPA4 as in embodiment (i).
Claim 26 further indicates that the antibody or antibody fragment specifically binds to Lp(a), and claim 27 further indicates that the antibody is polyclonal or monoclonal.
Claims 7, 24, and 30 further limit to an antibody or antibody fragment comprising CDRs having sequences of SEQ ID NOs: 4, 6, 8, 12, 14, and 16, but do not specify the order of CDRs or whether each occurs in the heavy chain or light chain, such that it is unclear if this limitation applies to antibody or antibody fragment (i), (ii), or both.
As such, the claims encompass a genus of antibodies or antibody fragments under alternative (i) which are defined by partial structure and binding function.
In contrast to the breadth of these claims which encompass a wide variety of structurally diverse antibodies, the instant specification provides description and reduction to practice of only one particular species of antibody (LPA KIV9, as shown in Table A).
Claim 8 recites an antibody or fragment thereof which is defined by its function of specifically binding to an epitope comprising the sequence of SEQ ID NO: 17. The specification contains description and reduction to practice of only one species of antibody that may fit this limitation (LPA-KIV9, as shown in Table A), though evidence in the prior art indicates that this antibody binds only to a partial sequence within SEQ ID NO: 17, as evidenced by Tsimikas et al (Generation and characterization of LPA-KIV9, a murine monoclonal antibody binding a single site on apolipoprotein (a). J Lipid Res. 2020 Sep;61(9):1263-1270), hereinafter Tsimikas ’20, which shows in Fig. 4 that the LPA-KIV9 antibody disclosed in the instant specification binds to the sequence LETPTVV, which is a smaller epitope within SEQ ID NO: 17. As such, it is not clear that the antibody disclosed in the application meets the requirement of the instant claim 8 that the antibody or antibody fragment binds to an epitope “comprising the sequence of SEQ ID NO: 17”, which appears to imply that the antibody should bind to at least the entire sequence.
Additionally, there is a general lack of structure-function correlation for the claimed antibodies and antibody fragments. The general structure of antibodies was known in the art before the effective filing date, and it was known that the CDRs of antibodies generally control antigen binding. While CDRs are necessary for binding, they are highly diverse in structure, and their sequences do not correlate to binding in a predictable fashion. See for instance:
Goel et al. (“Plasticity within the Antigen Combining Site May Manifest as Molecular Mimicry in the Humoral Immune Response,” The Journal of Immunology (2004), 173(12):7358-7367), who made three antibodies that bind to the same 12-mer but have very different CDRs.
Lloyd et al. (“Modelling the human immune response: performance of a 1011 human antibody repertoire against a broad panel of therapeutically relevant antigens,” Protein Engineering, Design & Selection (2009), 22(3):159-168) found that on average, about 120 different antibodies in a library can bind to a given antigen.
Edwards et al. (“The remarkable flexibility of the human antibody repertoire; isolation of over one thousand different antibodies to a single protein, BlyS,” Journal of Molecular Biology (2003), 334:103-118) found that a library contained over 1000 antibodies that bound to a single 51 kDa protein, including 1098 unique VH and 705 VL sequences. There were 568 different CDR3 regions, indicative of high diversity.
These references indicate that there was no art-recognized correlation between the structure of an antibody or binding agent and its binding properties. A single antigen can be bound by a very large and structurally diverse genus of antibodies and binding agents. There is no common structural relationship even for antibodies that bind the same protein sequence or the same epitope. Although the specification provides reduction to practice for one species of antibody, this antibody does not appear to fulfill the requirements of embodiment (i). The specification does not describe the structural characteristics common to the entire genus of antibodies and antibody fragments that display the binding specificity of antibody LPA4. The specification does not provide guidance as to what essential structures of antibodies or antibody fragments would confer the necessary claimed functions and does not allow one of ordinary skill in the art to visualize or recognize the members of the genus of antibodies or antibody fragments that would be able to achieve the claimed functions.
The lack of structure-function relationship and lack of predictability in the prior art discussed above is also relevant to claims 7, 24 and 30. Wherein the prior art shows that even very small changes to the structure of an antibody and its CDRs can significantly impact and change its binding function. As such, there is no particular evidence to support or reason to assume that any and all antibodies in the genus encompassed by claims 5, 7, 23-24 and 30 would be suitable for use in the methods as claimed. That is, there is no evidence that an antibody which comprises only some of the 6 recited CDRs or which comprises the same CDRs in a different order and configuration would fulfill the necessary function of specifically binding to apo(a) or Lp(a) as required by the independent claims.
Additionally, given the lack of predictability in the art, and the breadth of variation encompassed by the claims, disclosure antibody LPA4 in the instant application is insufficient to provide evidence of possession of the claimed genus as a whole. That is, antibody LPA4 itself is only one example of one antibody that fulfills the limitation of embodiment (i), but embodiment (i) encompasses any antibody or antibody fragment that displays the same binding specificity of LPA4. This is a much broader genus for which the essential structural elements are not disclosed in the application and for which the art is not predictable, such that disclosure of the single species is insufficient to indicate possession of the genus as a whole.
Dependent claims 2-3, 7-10, 12-13, 15-19, 22, 24, 26-27, 30-32, 34-36, and 38-39 are rejected because they depend from a rejected claim and fail to remedy its deficiencies.
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.
Claims 1, 6-10, 12-15, 17-19, 22, 24, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Kundu et al (US 2001/0051347 A1; IDS entered), hereinafter Kundu ‘01 in view of Tsimikas et al (Generation and characterization of LPA-KIV9, a murine monoclonal antibody binding a single site on apolipoprotein (a). J Lipid Res. 2020 Sep;61(9):1263-1270; previously cited), hereinafter Tsimikas ’20.
Regarding claims 1 and 6-8, 14, 24, and 30 Kundu ’01 teaches a method comprising:
Contacting a sample with an antibody or antibody fragment that specifically binds to apo(a) to obtain an apo(a)-antibody or antibody fragment complex; isolating the apo(a)-antibody or antibody fragment complexes; performing an assay on the isolated apo(a)-antibody or antibody fragment complexes to measure cholesterol (Par. 9, 18: method for determining amount of cholesterol associated with Lp(a) in a test sample comprising: contacting the sample with a monoclonal antibody or fragment thereof that specifically binds to kringle 5 of apo(a), wherein the antibody is coupled to a solid support; separating the solid support from the sample; and determining the amount of cholesterol bound to the solid support).
At Par. 66, Kundu ‘01 further teaches that methods for determining cholesterol associated with lipoproteins which may be used in the disclosed invention are well known to those of ordinary skill in the art, and that appropriate methods include those disclosed in Kundu ’93. Kundu ’93 teaches that these methods include measuring cholesterol by enzymatic colorimetric assays, as evidenced at Kundu ’93, Pg. 16.
Kundu ’01 does not specifically teach the method wherein the antibody comprises the specific CDR sequences or the specific VH and VL sequences recited in claim 6, and does not specifically teach that the antibody binds to an epitope having the sequence of SEQ ID NO: 17.
Tsimikas ’20 discloses antibodies or fragments thereof that specifically bind to apo(a) and which comprise VH and VL domain sequences of instant SEQ ID NOs: 2 and 10, and which comprise CDRs of SEQ ID NOs: 4, 6, 8, 12, 14, and 16, as required by the instant claims (Fig. 2).
Regarding claim 8, Tsimikas ‘20 discloses antibodies or fragments thereof that specifically bind to an epitope having the sequence of instant SEQ ID NO: 17 (Fig. 4).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Kundu to include the specific anti-apo(a) antibody taught by Tsimikas ‘20. Kundu ‘01 teaches a method comprising the use of an antibody that binds specifically to apo(a), and teaches that an antibody that binds to an epitope of apo(a) outside of the KIV2 domain (Par. 9). Tsimikas ’20 discloses antibodies and fragments thereof that specifically bind to an epitope of apo(a) in the KIV9 domain (Par. 7). As such, one of ordinary skill in the art would recognize that substitution of the antibody taught by Tsimikas ’20 for the antibody taught by Kundu ‘01 amounts to simple substitution of known elements to achieve predictable results with a reasonable expectation of success.
Regarding claims 9-10, 12, 15, and 17-18, Kundu ‘01 teaches the method wherein the binding molecule is linked to a substrate; wherein the substrate is an ELISA plate or a bead; and wherein the bead is a magnetic bead (Par. 18: antibody bound to a solid support; Par. 14: solid support may be a bead or magnetic particle).
Regarding claim 13, Kundu ‘01 further teaches the method wherein the sample is from a subject undergoing therapy for high cholesterol (Par. 102: cardiac patients taking lipid-lowering drugs).
Regarding claim 19, Kundu ’01 further teaches the method wherein the apo(a)-antibody complex is isolated using a magnet (Par. 14: antibody is bound to a solid support which may be a magnetic particle; Par. 18: antibody-apo(a)-solid support complex is separated from the sample; Par. 60: magnetic particles may be isolated from a sample by attraction to a magnet).
Regarding claim 22, Kundu ‘01 further teaches the method wherein the method determines the level of cholesterol in an apo(a) containing fraction of plasma (Par. 18, 22).
Claims 2, 25-27, 31-32, 34-36, and 38-39 are rejected under 35 U.S.C. 103 as being unpatentable over Kundu et al (US 2001/0051347 A1; IDS entered), hereinafter Kundu ‘01 in view of Tsimikas et al (Generation and characterization of LPA-KIV9, a murine monoclonal antibody binding a single site on apolipoprotein (a). J Lipid Res. 2020 Sep;61(9):1263-1270; previously cited), hereinafter Tsimikas ’20 as applied to claims 1 and 14 above, and further in view of Kundu et al (WO 1993/18067; IDS entered), hereinafter Kundu ‘93.
Regarding claims 2, 25 and 31, Kundu ‘01 teaches a method comprising:
Contacting a plasma sample with a composition or article of manufacture comprising a binding agent linked to a carrier, wherein the binding agent specifically binds to Lp(a), and wherein the carrier separate bound Lp(a) from a soluble fraction of the plasma (Par. 18).
Regarding claims 2 and 31, Kundu ’01 further teaches measuring the amount of cholesterol in the Lp(a)-C fraction to obtain and Lp(a)-C value (Par. 18).
Kundu ‘01 does not specifically disclose measuring the amount of cholesterol in the soluble fraction to obtain an LDL-C value.
Regarding claims 2, 25 and 31, Kundu ’93 teaches measuring the amount of cholesterol in a soluble fraction of plasma after removal of an Lp(a)-C fraction of plasma to thereby obtain an LDL-C value, wherein isolation and removal of the Lp(a)-C fraction from the sample allows for a more accurate determination of LDL-C levels (Pg. 5, Ln. 21-34: it is important that the Lp(a)-C correction be made in the LDL-C concentration because studies have shown that diet and drug treatment will reduce LDL-C levels but not Lp(a)-C levels, and proper patient monitoring requires an accurate measurement of LDL-C levels. This is particularly true for patient with elevated Lp(a). In such patients, the LDL-C values will be erroneous if no correction is made for Lp(a) cholesterol; Pg. 9, Ln. 7-11).
Both Kundu ’01 and Kundu ’93 teach that the amount of cholesterol in a particular fraction of a sample can be measured using an absorbance reading (Kundu ‘01, Par. 104-106; Kundu ’93, Pg. 53, Ln. 35-36, Pg. 64, Ln. 29-32, Pg. 72, Ln. 14-15).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method taught by Kundu ‘01 to further include measuring absorbance of the soluble fraction of plasma after removal of the Lp(a)-C fraction in order to obtain an LDL-C value. One of ordinary skill in the art would be motivated to make this modification for the purpose of obtaining a corrected LDL-C value which is more accurate because it does not comprise any Lp(a)-C, wherein this more accurate LDL-C value is useful for prognosis and monitoring, and wherein isolated values of both Lp(a)-C and corrected LDL-C are more useful in evaluating and monitoring cholesterol levels and treatments and associated risks of cardiovascular disease. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Kundu ‘01 and Kundu ’93 disclose methods of evaluating levels of cholesterol associated with specific lipoproteins using similar reagents and assays.
Regarding claims 26-27, Kundu ’01 further teaches the method wherein the binding agent is a polyclonal or monoclonal antibody that specifically binds to Lp(a) (Par. 18).
Regarding claim 32, Kundu ‘01 further teaches the method comprising measuring the amount of total cholesterol in the sample or in a corresponding sample prior to contacting the sample with the composition or article of manufacture to obtain an LDL-C value (Par. 102).
Regarding claim 34, Kundu ‘01 does not explicitly teach the method wherein Lp(a)-C value is subtracted from the total cholesterol value to obtain a corrected LDL-C value.
Regarding claim 34, Kundu ’93 teaches a method wherein the Lp(a)-C value is subtracted from the total cholesterol value to obtain a corrected LDL-C value (Pg. 5, Ln. 4-14).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Kundu ‘01 to further comprise subtracting the Lp(a)-C value from the total cholesterol value to obtain a corrected LDL-C value, as disclosed by Kundu ’93 for the benefit of having a corrected LDL-C value for proper patient monitoring and evaluation (Kundu ’93, Pg. 5, Ln. 21-34; Pg. 9, Ln. 7-11). Wherein this value can also be compared to the LDL-C value obtained in claim 25 to confirm the accuracy or observe variation in the measurements. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because both Kundu ’01 and Kundu ’93 are directed to methods of measuring levels of cholesterol associated with specific lipoproteins using similar reagents and assays.
Regarding claims 35-36, Kundu ‘01 further teaches the metho wherein the composition comprises a bead linked to the binding agent which may be a magnetic bead (Par. 14).
Regarding claims 38-39, Kundu ‘01 further teaches the method wherein the article of manufacture is a substrate comprising the binding agent, wherein the substrate may be a microwell plate (Par. 14, 49, 60, 104).
Claims 1, 3, 9-10, 12-19, 24 are rejected under 35 U.S.C. 103 as being unpatentable over Kundu et al (WO 1993/18067; IDS entered), hereinafter Kundu ’93 in view of Tsimikas et al (Percutaneous coronary intervention results in acute increases in oxidized phospholipids and lipoprotein(a): short-term and long-term immunologic responses to oxidized low-density lipoprotein. Circulation. 2004 Jun 29;109(25):3164-70; previously cited), hereinafter Tsimikas ‘04.
Regarding claims 1, 3, 9-10, 14-16, and 24, Kundu ‘93 teaches a method of assaying Lp(a)-C in a sample (Abstract; Pg. 8, Ln. 24-28: an object of the invention is to measure the plasma Lp(a)-C concentration of patients), the method comprising:
Contacting a sample with a binding molecule that specifically binds to apo(a) to obtain an apo(a) binding molecule complex; isolating the apo(a) binding molecule complexes; performing an assay on the isolate apo(a) binding molecule complexes to measure cholesterol (Pg. 68, Ln. 10-Pg. 69, Ln. 5: production of antibody 1E1 which binds specifically to apo(a); Pg. 71, Ln. 25-Pg. 72, Ln. 19: Lp(a)-C assay comprising: antibody 1E1 coated on a microwell plate is contacted with diluted plasma sample, then washed to remove unbound components; After washing HRPO-digitonin conjugate was added to each well and incubated, then washed; solution of o-phenylenediamine (substrate) is added to each well, and then quenched after 5 min; absorbance of each well is measured on a microplate reader, and Lp(a)-C concentration was then determined from a standard curve of absorbance vs Lp(a)-C concentration).
Kundu ’93 does not specifically teach the method wherein the binding molecule comprises light chain and heavy chain CDRs of an LPA4 antibody.
Regarding claim 3, Tsimikas ‘04 teaches measurement of Lp(a) in plasma using a chemiluminescent ELISA comprising the murine monoclonal antibody LPA4 which binds specifically to an epitope of apo(a) (Pg. 3165, Col. 1, Par. 5). Wherein the LPA4 antibody taught by Tsimikas ‘04 is understood to inherently comprise light chain and heavy chain CDRs of an LPA4 antibody.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method taught by Kundu ‘93 to comprise the LPA4 antibody taught by Tsimikas ‘04. Kundu ‘93 teaches a measurement method comprising the use of an antibody that specifically binds to apo(a). Similarly, Tsimikas ‘04 teaches a monoclonal antibody LPA4 which binds specifically to apo(a), and which can be used in an immunoassay to bind and measure Lp(a). As such, one of ordinary skill in the art would recognize from the teachings of these references that substitution of the LPA4 antibody taught by Tsimikas ‘04 for the antibody taught by Kundu ‘93 amounts to simple substitution of known elements to achieve predictable results with a reasonable expectation of success.
Regarding clims 10, 12, 15, and 17-19, Kundu ’93 further teaches that the apo(a) binding molecule may be bound to a substrate which may be a magnetic bead, and teaches that the apo(a)-antibody complex may be isolated using a magnet (Abstract: the specific lipoprotein binding agent can be bound to a solid support; Pg. 14, Ln. 33-36: the solid support may be a bead or magnetic particle; Pg. 15, Ln. 1-20: magnetic particles can be isolated from the sample using magnetic attraction).
Regarding claim 13, Kundu ’93 further teaches assay methods comprising samples from patients undergoing therapy for high cholesterol (Pg. 46, Ln. 3-5: assay evaluated with patient samples who are on lipid lowering drugs; Table 9), though it is noted that in the examples provided in the reference, these samples are used in an assay for measuring LDL-C instead of Lp(a)-C. However, Kundu ’93 further teaches that it is important to monitor and accurately measure Lp(a)-C in this population (i.e. patient undergoing therapy for high cholesterol) (Pg. 5, Ln. 21-26: it is important that Lp(a)-C correction be made in the LDL-C concentration because studies have shown that diet and drug treatment will reduce LDL-C cholesterol levels but not Lp(a) cholesterol levels and proper patient monitoring requires accurate measurement; Pg. 8, Ln. 23-28: The effect of diet and lipid lowering drugs on Lp(a)-C levels is not known. An object of the present invention is to measure the plasma Lp(a)-C concentration of patients easily and accurately to allow researchers to further investigate the relationship between Lp(a)-C concentrations and CHD).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Kundu ’93 to specifically comprise the use of samples from patients undergoing therapy for high cholesterol in the method of assaying Lp(a)-C. One of ordinary skill in the art would be motivated to make this modification for the purpose of tracking and investigating the effects of lipid-lowering drugs on Lp(a)-C concentration in a patient. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because Kundu ’93 discloses similar assays using samples from this patient population.
Response to Arguments
Applicant’s arguments filed 13 February 2026 have been fully considered.
Prior objections to the specification are overcome by the amendments to the specification and are withdrawn.
Regarding the 112(a) rejection, applicant argues that the amendments to the claims overcome the previous 112(a) rejection. The previous 112(a) rejection is withdrawn in favor of the new grounds of 112(a) rejection presented above which address the amended claims.
The previous 112(b) rejections are overcome by the amendments to the claims and are withdrawn.
The previous 112(d) rejection is overcome by cancellation of rejected claim 20 and is withdrawn.
Regarding the 102 and 103 rejections: the previous grounds of 102 and 103 rejections are withdrawn in favor of the new grounds of 103 rejection presented above, as necessitated by the amendments to the claims. Applicant’s arguments which are relevant to the new grounds of 103 rejection are addressed here.
Regarding claim 3, applicant asserts that “the LPA4 antibody was not developed until 2021”. This assertion appears to be inaccurate, as the LPA4 antibody was disclosed at least in Tsimikas ’04, as cited above, which was published in 2004.
Regarding the combination of Kundu ’93 and Tsimikas ’04, applicant argues that Kundu ’93 does not use antibodies to Lp(a), such that there is no motivation to look to antibodies for Lp(a). This argument is not persuasive, as Kundu ’93 explicitly discusses preparation of monoclonal antibodies specific for Lp(a) (Pg. 68, Example 14) and explicitly discusses the use of such antibodies in an Lp(a)-C assay Pg. 71, Example 17). Applicant further argues that Tsimikas does not provide any indication as to the specificity of the LPA4 antibody, or to which the KIV domains the antibody binds or sequence information. This argument is not persuasive. Kundu ’93 discloses an Lp(a)-C assay which comprises the use of monoclonal antibodies raised against apo(a) peptides, then indicates that these can be used in an assay to specifically bind to apo(a). Kundu’93 does not specify any other more specific binding requirement. Tsimikas ’04 indicates that LPA4 is a monoclonal antibody raised against a peptide of apo(a) which can be used in an assay to specifically bind to apo(a). Applicant argues that there is not a predictable expectation of success in making this combination and that one of ordinary skill in the art would have to perform experiments by trial and error to develop the presently claimed invention, but has not provided specific reasoning or evidence to support this assertion. Applicant further argues that this is supported by the fact that it took almost 27 years from the publication of Kundu’93 and 16 years from the publication of Tsimikas ’04 to develop the present invention. This argument is not persuasive. The fact that the particularly claimed invention had not been specifically and explicitly anticipated by a single reference prior to the instant application does not overcome the obviousness rejection, as a combination of prior art references and teachings is the basis of all obviousness rejections.
Regarding the combination of Kundu ’01 and Tsimikas ’20, applicant argues that Kundu ’01 does not teach the antibody of the amended independent claims, and argues that Tsimikas ’20 does not provide teaching with respect to measuring cholesterol or Lp(a) cholesterol. Further, applicant argues that one of skill in the art would have to perform experiments by trial and error to develop the presently claimed invention, as there was no predictability of success. These arguments are not persuasive.
Tsimikas ’20 is not relied upon to teach a method of measure cholesterol or Lp(a) cholesterol. Tsimikas ’20 is only relied upon to teach a particular antibody which is taught to specifically bind apo(a). There is a reasonable expectation of success in combining the references because Kundu ’01 teaches a method comprising the use of an antibody that binds specifically to apo(a) within specific domains (Par. 9) and Tsimikas teaches an alternative antibody that is also known to bind specifically to apo(a) in a domain which is compatible with the teachings of Kundu ‘01, such that both antibodies would be reasonably expected to serve the same function of binding apo(a) within the method disclosed by Kundu ‘01. Applicant has not identified what in particular about the combination of prior art would be unpredictable or would lack a reasonable expectation of success, and has not provided particular evidence or showing to support this claim.
Applicant further submits that Tsimikas ’20 is a publication by the inventor less than 12 months prior to the priority date of the present application. This statement does not satisfactorily disqualify Tsimikas ’20 as prior art applied to the instant application because it does not meet the criteria required of a proper affidavit or declaration under 37 CFR 1.130(a) to overcome the reference. See MPEP 717.01 (in particular 717.01(a)(1)) and MPEP 2132.01(I).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 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.
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/ELLIS FOLLETT LUSI/Examiner, Art Unit 1677
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677