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 .
Claim Rejections - 35 USC § 112
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 1-19 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The claims require:
--γH2AX antibody (in claim 1, line 8);
--drug impurities of different DNA damage mechanisms (in claim 8, lines 7-8);
--an effector molecule overexpressed at a [gene] damage (in claim 9, line 2);
--effector molecules (in claim 10, lines 6-7);
--drug impurities of different DNA damage mechanisms (in claim 16, lines 7-8);
--drug impurities of different DNA damage mechanisms (in claim 17, lines 7-8);
--drug impurities of different DNA damage mechanisms (in claim 18, lines 7-8);
--drug impurities of different DNA damage mechanisms (in claim 19, lines 7-9).
The specification does not describe which amino acid residues, nucleic acid residues or other molecular components are responsible for the functions claimed. Potential agents must first be screened in an assay to ascertain if the agents have the functions required by the instant claims. The specification fails to disclose the structures common to all members of the genus of peptides encompassed by the broad definition provided by applicant. The specification does not disclose the structure of all of the claimed variant agents and fails to disclose which regions of the agents are responsible for the functions claimed. In the absence of a known or disclosed correlation between structure and function, claims which encompass variants defined by their function are generally not considered described.
Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement. Here, applicant has not described a reasonable number of members of the genus of agents that bind to α-syn PFF, i.e. the required starting materials for the claims, but rather has presented the public with an idea of how to perform an assay that might identify some peptides that fall within the scope of the claim. Of course, depending on what agents are used in the screening assay, it may well identify none. The Court of Appeals for the Federal Circuit addressed claims of this sort in great detail in University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004). In Rochester, the Federal Circuit upheld the district court's ruling that patent claims which recited administration of compounds not disclosed, but rather to be identified in a screening assay, were invalid on their face.
The specification does not describe the structure of the full genus of antibodies, or drug impurities of different DNA damage mechanisms, or the recited effector molecules, responsible for each of the functions claimed. The Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of an antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
While generically the structure of antibodies is known, the structure of the presently recited antibodies can vary substantially within the above given claimed recitations. As noted in Amgen, knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted). The relevant antibody art confirms this quandary, indicating that “knowledge of an epitope or antigen used to generate a monoclonal antibody is insufficient for making the original antibody available, even if suitable in vitro test systems for screening are used.” See p. 8, lines 3-5 of WO 2009/033743 A1. Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of antibodies presently claimed.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed antibodies, or drug impurities of different DNA damage mechanisms, or the recited effector molecules, nor guidance as to which of the myriad of molecules encompassed by the recited agents would meet the limitations of the claims. Further, given the well-known high level of polymorphism of immunoglobulins and antibodies, the skilled artisan would not have recognized that applicant was in possession of the vast repertoire of antibodies encompassed by the claimed invention.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), clearly states that “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 purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The skilled artisan cannot envision the detailed chemical structure of the genus of agents, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). Therefore, the instant claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
The remaining claims are rejected for failing to meet written description requirements since they depend from one of the claims above without rectifying the issues identified above.
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 1-19 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.
Claim 1 recites in lines 1-4 “a cell-based sensor based on surface-enhanced Raman scattering, wherein the cell-based sensor is established by….; the surface-enhanced Raman scattering probe is prepared by using….” The claim does not use a word like “comprising”, and therefore it is not clear as to what the sensor includes and does not include.
As a separate matter, it is also not clear as to what is considered the claimed “cell-based sensor”. For example, is the result of all the steps recited claim 1 lines 1-12 considered the ‘cell-based sensor”? For example, must the result of the preparations in lines 4-10 be guided into a human liver cell line be performed in order for it to be considered the claimed “cell-based sensor” (as appears to be indicated in lines 2-3), or do the preparations in lines 4-10 result in a “cell-based sensor”? In other words, does claim 1 require that the probe (of line 4) be guided into a human liver cell line in order to be the claimed cell-based sensor (as appears to be indicated in lines 2-3)?
The term “ultrapure” in claim 2 is a relative term which renders the claim indefinite. The term “ultrapure” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Ultrapure appears to be referring to ultra pure, or very pure. The term “ultra” is a relative term, and therefore ultrapure is a relative. It is not clear as to what constitutes “ultrapure” since it is a relative term and the specification does not provide a standard for ascertaining the requisite degree.
The term “quickly” in claim 2 is a relative term which renders the claim indefinite. The term “quickly” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 8 recites “A genotoxic impurity assessment method based on surface-enhanced Raman scattering, wherein the method uses……” However, there is no term like “comprising” in the claim, and therefore it is not clear as to what the claim includes (or does not include).
Claim 9, line 2, recites “an effector molecule is overexpressed at the damage”. It is not clear if this effector molecule is the same as the gene damage effector molecule antibody in claim 8, line 3, and gene damage effector molecule antibody in claim 1, line 5.
Claim 10, lines 1-3, recites “wherein a concentration of the drug impurities is supposed to ensure that a cell viability of the cell-based sensor is 75% or above”. This limitation is not clear. It is not clear as to what is meant by “is supposed to ensure”. It is not clear how the concentration of drug impurities is supposed to ensure a cell viability as recited. It is not clear if this limitation is a step or implies an active step in the claimed invention.
Claim 10, lines 3-4, recites, “when the Raman signal is detected, an excitation wavelength of a light source of the Raman spectrometer is 638 nm”.
The claim lacks sufficient antecedent basis for “the Raman spectrometer”. It is not clear if “the Raman spectrometer” is required by the claimed invention in addition to the cell-based sensor of claim 1 (from which claim 10 ultimately depends), or whether “the Raman spectrometer” is part of the cell-based sensor of claim 1.
It is not clear if the claimed invention requires an active step of detecting a Raman signal, and an active step of providing a light source at 638 nm in a Raman spectrometer.
Claim 10, lines 4-5, recites “the detected signal uses a peak value of a characteristic Raman peak after 1800 cm-1 of a Raman shift”. It is not clear as to how a detected signal uses a peak value…. It is not clear as to what active step of the claimed invention is required here, if any.
Claim 10, lines 5-6, recites “the detected signal is transformed to an effector molecule concentration through a standard curve”. It is not clear as to what active steps of the claimed invention is required here. It is not clear if Applicant intends for there to be an active step here as part of the claimed invention. It is not clear if the effector molecule” in claim 10, line 6 is the same as the gene damage effector molecule antibody recited in claim 1, line 5.
Claim 10, lines 6-7, recites “a concentration ration of effector molecules of a test group and a control group is calculated”. It is not clear if Applicant intends for there to be an active step here as part of the claimed invention.
Claim 10, lines 7-9, recites “namely, a fold of induction (FI), when FI is greater than 1.5, it is judged as a DNA-damage type genotoxic impurity, and when FI is smaller than or equal to 1.5, it is judged as a non-DNA-damage type genotoxic impurity”. It is not clear if Applicant intends for there to be an active step here as part of the claimed invention, and what active steps that would be.
Also it is not clear as to what “it” is. For examination purposes, “it” in lines 7-9 is interpreted to be the genotoxicity level of the drug impurities (see claim 8, lines 8-9.)
Claims 12-15 each are directed to a method, but do not recite any active steps. There is no ‘body’ to each of these claims. Therefore it is not clear as to what steps these claims require.
Claim 16 recites a method, but there is no term like “comprising” to understand what is encompassed (or not encompassed) by the method.
Claim 16 recites:
“A genotoxic impurity assessment method based on surface-enhanced Raman scattering, wherein the method uses…” There is no term like “comprising” to understand what is encompassed (or not encompassed) by the method.
Claim 16 recites a “genotoxic impurity assessment method based on surface-enhanced Raman scattering, wherein the method uses the gold nanoparticle as the testing substrate, the gene damage effector molecule antibody as the recognition unit, the Raman molecule as the reporting unit, SH-PEG-NH2 as the stable chain and the cell-penetrating peptide as the auxiliary penetration unit to prepare the surface-enhanced Raman scattering probe; the surface-enhanced Raman scattering probe is guided into the human liver cell line to establish the cell-based sensor; the cell-based sensor is exposed to drug impurities of different DNA damage mechanisms, the Raman signal is detected, and the genotoxicity level of the drug impurities is assessed; and the cell-based sensor is the cell-based sensor according to claim 2.” These limitations are recited in the passive tense, and it is not clear if these are active steps required by the recited invention.
Also, claim 16, lacks sufficient antecedent basis for:
“the gold nanoparticle” in line 2;
“the gene damage effector molecule antibody” in line 3;
“the Raman molecule” in line 3;
“the stable chain” in line 4;
“the cell-penetrating peptide” in line 4;
“the surface-enhanced Raman scattering probe” in line 6;
“the human liver cell line” in line 6;
“the genotoxicity level of the drug impurities” in lines 7-8;
“the cell-based sensor” in line 7;
“the Raman signal” in line 8.
While claim 16 recites in the last line “the cell-based sensor is the cell-based sensor according to claim 2” [which thus appear to provide sufficient antecedent basis for the above-mentioned limitations], however the above-mentioned limitations are recited the body of claim 2 as part of the method of making the cell-based sensor, whereas claim 16 recites an “assessment method”. Thus, claim 16 appears to lack sufficient antecedent basis for the above-mentioned limitations.
Claim 17 recites:
“A genotoxic impurity assessment method based on surface-enhanced Raman scattering, wherein the method uses…” There is no term like “comprising” to understand what is encompassed (or not encompassed) by the method.
Claim 17 recites:
“A genotoxic impurity assessment method based on surface-enhanced Raman scattering, wherein the method uses the gold nanoparticle as the testing substrate, the gene damage effector molecule antibody as the recognition unit, the Raman molecule as the reporting unit, SH-PEG-NH2 as the stable chain and the cell-penetrating peptide as the auxiliary penetration unit to prepare the surface-enhanced Raman scattering probe; the surface-enhanced Raman scattering probe is guided into the human liver cell line to establish the cell-based sensor; the cell-based sensor is exposed to drug impurities of different DNA damage mechanisms, the Raman signal is detected, and the genotoxicity level of the drug impurities is assessed; and the cell-based sensor is the cell-based sensor according to claim 4.”
These limitations are recited in the passive tense, and it is not clear if these are active steps required by the recited invention.
Also, claim 17, line 7, lacks sufficient antecedent basis for “the cell-based sensor”.
Also, claim 17, lacks sufficient antecedent basis for:
“the gold nanoparticle” in line 2;
“the gene damage effector molecule antibody” in line 3;
“the Raman molecule” in line 3;
“the stable chain” in line 4;
“the cell-penetrating peptide” in line 4;
“the surface-enhanced Raman scattering probe” in line 6;
“the human liver cell line” in line 6;
“the genotoxicity level of the drug impurities” in lines 8-9;
“the Raman signal” in line 8; and
“the cell-based sensor” in line 9.
While claim 17 recites in the last line “the cell-based sensor is the cell-based sensor according to claim 4” [which thus appear to provide sufficient antecedent basis for the above-mentioned limitations], however the above-mentioned limitations are recited in claim 4 as part of the method of making the cell-based sensor, whereas claim 16 recites an “assessment method”. Thus, claim 17 appears to lack sufficient antecedent basis for the above-mentioned limitations.
Claim 18 recites:
“A genotoxic impurity assessment method based on surface-enhanced Raman scattering, wherein the method uses…” There is no term like “comprising” to understand what is encompassed (or not encompassed) by the method.
Claim 18 recites:
“A genotoxic impurity assessment method based on surface-enhanced Raman scattering, wherein the method uses the gold nanoparticle as the testing substrate, the gene damage effector molecule antibody as the recognition unit, the Raman molecule as the reporting unit, SH-PEG-NH2 as the stable chain and the cell-penetrating peptide as the auxiliary penetration unit to prepare the surface-enhanced Raman scattering probe; the surface-enhanced Raman scattering probe is guided into the human liver cell line to establish the cell-based sensor; the cell-based sensor is exposed to drug impurities of different DNA damage mechanisms, the Raman signal is detected, and the genotoxicity level of the drug impurities is assessed; and the cell-based sensor is the cell-based sensor according to claim 5.
These limitations are recited in the passive tense, and it is not clear if these are active steps required by the recited invention.
Also, claim 18, line 7, lacks sufficient antecedent basis for “the cell-based sensor”.
Also, claim 18, lacks sufficient antecedent basis for:
“the gold nanoparticle” in line 2;
“the gene damage effector molecule antibody” in line 3;
“the Raman molecule” in line 3;
“the stable chain” in line 4;
“the cell-penetrating peptide” in line 4;
“the surface-enhanced Raman scattering probe” in line 6;
“the human liver cell line” in line 6;
“the genotoxicity level of the drug impurities” in lines 8-9;
“the Raman signal” in line 8; and
“the cell-based sensor” in line 9.
While claim 18 recites in the last line “the cell-based sensor is the cell-based sensor according to claim 5” [which thus appear to provide sufficient antecedent basis for the above-mentioned limitations], however the above-mentioned limitations are recited in claim 5 as part of the method of making the cell-based sensor, whereas claim 18 recites an “assessment method”. Thus, claim 18 appears to lack sufficient antecedent basis for the above-mentioned limitations.
Claim 19 recites:
“A genotoxic impurity assessment method based on surface-enhanced Raman scattering, wherein the method uses…” There is no term like “comprising” to understand what is encompassed (or not encompassed) by the method.
Claim 19 recites:
“A genotoxic impurity assessment method based on surface-enhanced Raman scattering, wherein the method uses the gold nanoparticle as the testing substrate, the gene damage effector molecule antibody as the recognition unit, the Raman molecule as the reporting unit, SH-PEG-NH2 as the stable chain and the cell-penetrating peptide as the auxiliary penetration unit to prepare the surface-enhanced Raman scattering probe; the surface-enhanced Raman scattering probe is guided into the human liver cell line to establish the cell-based sensor; the cell-based sensor is exposed to drug impurities of different DNA damage mechanisms, the Raman signal is detected, and the genotoxicity level of the drug impurities is assessed; and the cell-based sensor is the cell-based sensor according to claim 6.”
These limitations are recited in the passive tense, and it is not clear if these are active steps required by the recited invention.
Also, claim 19, line 7, lacks sufficient antecedent basis for “the cell-based sensor”.
Also, claim 19, lacks sufficient antecedent basis for:
“the gold nanoparticle” in line 2;
“the gene damage effector molecule antibody” in line 3;
“the Raman molecule” in line 3;
“the stable chain” in line 4;
“the cell-penetrating peptide” in line 4;
“the surface-enhanced Raman scattering probe” in line 6;
“the human liver cell line” in line 6;
“the genotoxicity level of the drug impurities” in lines 8-9;
“the Raman signal” in line 8; and
“the cell-based sensor” in line 9.
While claim 19 recites in the last line “the cell-based sensor is the cell-based sensor according to claim 6” [which thus appear to provide sufficient antecedent basis for the above-mentioned limitations], however the above-mentioned limitations are recited in claim 6 as part of the method of making the cell-based sensor, whereas claim 19 recites an “assessment method”. Thus, claim 19 appears to lack sufficient antecedent basis for the above-mentioned limitations.
The remaining claims are rejected since they depend from one of the claims above, without clarifying the issues identified above.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US 20110111518. This reference nanoparticles and methods of making the nanoparticles having Raman enhancements. See abstract.
HS-PEG-SH, HS-PEG-COOH or HS-PEG-NH2. were utilized to coat the fluorescent silver nanoparticles to obtain nanoparticles coated with PEG molecules. Para. 0096.
The stability of silver nanoparticles in the different PEG molecules coatings in the different solutions were investigated using a particle analyzer. No aggregation was observed when the particles were dissolved in PBS or NaCl. The fluorescence property of these nanoparticles was not affected by these coatings. Since these PEG molecules also have functional groups such as SH, NH2, and COOH, these nanoparticles can be further linked to antibodies, specific ligands that can target the proteins or nucleic acids molecules of the live cells. Para. 0097.
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/Ann Montgomery/Primary Examiner, Art Unit 1678
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