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 .
This is the First Office Action on the Merits of US18/615987 filed on 03/25/2024 which is a DIV of 16/667,016 filed on 10/29/2019 (now US Patent 11940452) which is a CON of 15/788,876 filed on 10/20/2017 (now US Patent 10466260) which is a DIV of 14/858,111 filed on 09/18/2015 (now US Patent 9810702) which claims US priority benefit of US Provisional 62/052,854 filed on 09/19/2014.
Claims 21-40 are pending and under examination.
Information Disclosure Statement
The IDS filed on 03/25/2024 has been considered by the examiner. The references: Vallance et al; "Google search of HDP associated proteins"; Bergt; Huang; Shao; and Davidsson et al have been found in the priority application 14/858,111 and have been considered. The references: Calvete et al; "Website: 2013"; and Gupta et al, 2005, have been found in the priority application 15/788,876 and have been considered.
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.
Claims 21-40 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.
Regarding claims 21 and 33, a broad range or limitation together with a narrow range or 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, claims 21 and 33 each recite the broad recitation “an immunoassay”, and the claims also recites “(e.g., ELISA)” 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.
Claims 22-31 are indefinite for the same reasoning because they depend from claim 21 and are not remedial.
Also, regarding base claims 21 and 32, there is insufficient antecedent basis for the term “the mixture” recited in step (c) of each of claims 21 and 32 because the claims recite a mixture in step (a) and a modified “mixture” in step (b). It would be remedial to amend the claims 21 and 32 to recite …the mixture of step b)...
Claims 22-31 and 33-40 are indefinite as they depend from claims 21 and 32 and are not remedial.
Also, regarding claims 27-28 (line 2), there is insufficient antecedent basis for the term “the first mixture”. Claim 26 does not recite a mixture. Claim 26 depends from claim 21 which recites “a mixture” in step a) but does not explicitly recite a first mixture. It would be remedial to refer to the intended mixture of claim 21 by the step (such as ..the mixture of step a)…
Also, regarding claim 27, the parameters for the % amount of the separating solution is unclear because the claim recites that the separating solution makes up greater than 50% of the first mixture. Greater than 50% encompasses 100% of the first mixture.
Scope of enablement
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.
Claims 21-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of detecting an HDL-associated protein selected from the list recited in claim 32, does not reasonably provide enablement for detecting any HDL-associated protein following the method steps of claims 21-31. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The following factors have been considered in the analysis of enablement: (1) the breadth of the claims, (2) the nature of the invention, (3) the state of the prior art, (4) the level of one of ordinary skill, (5) the level of predictability in the art, (6) the amount of direction provided by the inventor, (7) the existence of working examples, (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. (See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1998) as appropriate. See also MPEP §§ 2164.01(a) and 2164.04.)
The breadth of the claims is to any HDL-associated protein, including as yet unknown “HDL-associated protein”.
The nature of the invention is a method of extracting and detecting at least one HDL-associated protein comprising: a) mixing, in a first container, a separating solution and a serum or plasma sample to generate a first mixed sample, wherein said separating solution comprises a strong organic acid and a hydrophilic organic solvent, and wherein said separating solution makes up greater than 55% to 93% of said first mixed sample; b) exposing said first mixed sample to centrifugal force such that said first mixed sample separates into a pellet and supernatant; c) transferring at least a portion of said supernatant to a second container such that it is separated from said pellet; d) adding a non-polar organic solvent to said second container at a ratio of greater than 1:1 to generate a second mixed sample; e) exposing said second mixed sample to centrifugal force such that said second mixed sample separates into an upper organic solvent layer and a bottom aqueous layer; f) transferring at least a portion of said bottom aqueous layer to a third container such that it is separated from said upper organic solvent layer; and g) subjecting at least a portion of said bottom aqueous layer to a detection assay such that at least one HDL-associated protein is detected.
The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The state of the art is shown in Davidsson et al in “Proteomics of apolipoproteins and associated proteins from plasma high-density lipoproteins” (Arterioscler Thromb Vasc Biol. 2010, Vol. 30, pages 156-163; IDS ref). Davidsson et al disclose that the structure /function of HDL-associated proteins is substantially distinct from person to person and patient to control population. For example, in the Abstract, Davidsson et al recite:
Proteomics studies have extended the list of identified apolipoproteins and associated proteins present in HDL and its subclasses. These proteins appear to cluster around specific functions related to lipid metabolism, inflammation, the immune system, hormone-binding, hemostasis, and antioxidant properties. Small studies suggest that there are substantial differences between the HDL proteome from cardiovascular disease patients and that from controls. Furthermore, dyslipidemia therapy shifts the HDL proteome from patients toward the profile observed in healthy controls. In addition, the proteome of HDL and LDL from patients with insulin resistance and peripheral atherosclerosis show significant differences with that of matched healthy controls. The proteome of HDL and LDL density subclasses have apolipoproteins and associated proteins profiles that suggest subclass- specific functions. However, proteomics studies of lipoproteins are few and small and should be interpreted with caution.
Davidsson et al disclose that:
The classical apolipoproteins have structural functions and provide recognition signals that control the interactions of lipoproteins with cells and tissues. All lipoproteins, in addition, contain surface-associated proteins that also appear to participate in their multiple functions. Recent proteomic studies have extended the number of identified associated proteins and show that HDL and LDL subclasses have unique profiles that may modulate specific functions. Abnormalities of some apolipoproteins, as decrease of apoAI in HDL and increase of apoB 100 and apoCIII in LDL, have been well documented to be associated with risk of ACVD. The discussed proteomics studies suggest that alterations of many apolipoproteins and multiple associated proteins also may be present in patients with coronary atherosclerosis and dyslipidemias and in subjects with peripheral atherosclerosis and the dyslipidemia of insulin resistance. (See page 162, column 1).
Thus Davidsson et al provides evidence that the state of the art before the effective filing date of the presently claimed invention showed that an extraction and detection method as claimed here to extract and detect any and all HDL-associated proteins was unpredictable because the structure of HDL-associated proteins was unpredictable. The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification.
The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). It is considered that the level of skill in the art was high, at the level of a PhD or MD research scientist.
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability.” (MPEP 2164.03). In the instant case, it was unpredictable before the effective filing date of the claimed invention whether a given protein would be considered an HDL-associated protein without performing trial and error experimentation. Further, it was unpredictable whether such HDL-associated protein would be detectable by the presently claimed method.
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. >See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004). In the instant case, the specification is drawn to a protein extraction and detection method for HDL-associated proteins contained in a plasma or serum sample. ApoA1 is noted as an exemplary type of HDL-associated protein. The specification discloses a set of HDL-associated proteins listed in Table 1 and recited in claims 21 and 24 for extraction and detection using the claimed method. The specification discloses a “gold standard” method for isolating HDL proteins from serum in paragraph 0004. In paragraph 0007, the specification discloses that the HDL-associated protein is listed in Table 1. A preferred embodiment is human ApoA1.
The term “HDL” is defined in the specification as follows:
[0014] As used herein, "high density lipoprotein" or "HDL" is a circulating, non-covalent assembly of amphipathic proteins that enable lipids like cholesterol and triglycerides to be transported within the water-based bloodstream. HDL is composed of about 50% by mass amphipathic proteins that stabilize lipid emulsions composed of a phospholipid monolayer (about 25%) embedded with free cholesterol (about 4%) and a core of triglycerides (about 3%) and cholesterol esters (about 12%). Subclasses of HDL include HDL2 and HDL3. HDL2 particles are larger and contain a higher content of lipid whereas HDL3 particles are smaller and contain less lipid. Further subclasses include from largest particle to smallest particle, HDL2b, HDL2a, HDL3a, HDL3b, and HDL3c.
While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), the lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art. The working embodiment in the instant application describes HDL-associated proteins but does not disclose how to determine whether a given protein is considered to be an HDL-associated protein without performing trial and error experimentation. The specification does not provide a definition for the claim term HLA-associated protein.
Without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the full-scope of the presently claimed invention. Therefore, it is considered that the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Double Patenting - Statutory
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 21, 23, 24, and 33 are rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1, 4, 5, and 13 of prior U.S. Patent No. 10,466,260 B2. This is a statutory double patenting rejection.
Instant claim 21 claims the same invention as patented claim 1.
Instant claim 23 claims the same invention as patented claim 4.
Instant claim 24 claims the same invention as patented claim 5.
Instant claim 33 claims the same invention as patented claim 13.
Double Patenting - NSDP
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 21-24, 32-36, and 39-40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,466,260 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims are essentially the same as or anticipate the present claims. (See Statutory DP above for claims 21, 23, 24, and 33.)
Regarding instant claim 21, patented claim 1 recites the same invention as instant claim 21 being a method comprising:
a) mixing a sample with a buffer solution and a pH sensitive protease to generate a mixture, wherein the sample comprises a purified high density lipoprotein (HDL)-associated protein, and wherein the pH of the buffer solution changes based on temperature;
b) incubating the mixture at a first temperature that causes the buffer to have a first pH, wherein the first pH is in the optimum activity range of the pH sensitive protease such that the pH sensitive protease digests the purified HDL-associated protein generating protein fragments;
c) incubating the mixture at a second temperature that causes the buffer to have a second pH, wherein the second pH is outside the optimum activity range of the pH sensitive protease thereby reducing the activity of the pH sensitive protease; and
d) subjecting the mixture of step c) to a detection method selected from mass spectrometry, liquid chromatography, surface plasmon resonance, an in vitro assay, an activity assay, co-immunoprecipitation assay, Fluorescence Energy Transfer (FRET), bioluminescence energy transfer (BRET), an immunoassay (e.g., ELISA), interferometry, Ellipsometry, and Quartz Crystal Microbalance, such that the peptide fragments are detected, thereby detecting, the purified HDL-associated protein.
Regarding instant claims 22 and 34, patented claim 7 recites LysC.
Further, instant claim 23 recites the same invention as patented claim 4.
Further, instant claim 24 recites the same invention as patented claim 5.
Regarding instant claim 32, patented claim 13 anticipates claim 32.
Further, instant claim 33 is the same invention as patented claim 13.
Regarding instant claim 35, patented claim 9 recites a first temperature of about 37 degrees Celsius.
Regarding instant claim 36, patented claims 10 recites a second temperature of about 4 degrees Celsius.
Regarding instant claims 39-40, patented claims 14 recites the detection method comprises mass spectrometry which does not require ultracentrifugation.
Conclusion
No claim is allowed.
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/CATHERINE S HIBBERT/ Primary Examiner, Art Unit 1658
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