Ex Parte Tammaji et alDownload PDFPatent Trial and Appeal BoardFeb 11, 201311986908 (P.T.A.B. Feb. 11, 2013) Copy Citation UNITED STATES PATENT AND TRADEMARKOFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 11/986,908 11/27/2007 Kulkarni Sanjay Tammaji 285.137 4846 90948 7590 02/11/2013 Charles Muserlain 317 Bliss Lane Valley Cottage, NY 10989 EXAMINER BOYLE, ROBERT C ART UNIT PAPER NUMBER 1764 MAIL DATE DELIVERY MODE 02/11/2013 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________________ Ex parte KULKARNI SANJAY TAMMAJI, VELURY RAMKRISHNA, PRABHU GORPALLY VITOBA, RANGACHARI GOPINATH and MUTHIAH RAMAKRISHNAN ____________________ Appeal 2012-000438 Application 11/986,908 Technology Center 1700 ____________________ Before FRED E. McKELVEY, MICHAEL P. COLAIANNI and GRACE KARAFFA OBERMANN, Administrative Patent Judges. McKELVEY, Administrative Patent Judge. DECISION ON APPEAL Appeal 2012-000438 Application 11/986,908 2 Statement of the case Futura Polyester Ltd. (“applicant”), the real party in interest (Brief, page 1), 1 seeks review under 35 U.S.C. § 134(a) of a final rejection dated 23 July 2010. 2 The application was filed in the USPTO on 27 November 2007. 3 The application on appeal claims priority of Indian Patent Application 4 1953/MUM/2006, filed 28 November 2006. 5 The application has been published as U.S. Patent Application Publication 6 2009/0036613 A1 (“Tammaji”). 7 In support of prior art rejections maintained in the Answer, the Examiner 8 relies on the following evidence. 9 Iohara et al. “Iohara” U.S. Patent 4,410,473 18 Oct. 1983 Johnson et al. “Johnson” U.S. Patent Application Publication 2003/0003299 A1 02 Jan. 2003 Applicant does not contest the prior art status of the evidence relied upon by 10 the Examiner. 11 On page 2 of the Reply Brief, applicant mentions the following evidence, 12 viz., the published version of the application on appeal. 13 Tammaji et al. “Tammaji” U.S. Patent Application Publication 2009/0036613 A1 5 Feb. 2009 We mention the following additional evidence in this opinion. 14 Appeal 2012-000438 Application 11/986,908 3 Stevens POLYMER CHEMISTRY 50-53 (Oxford University Press) (3d ed.) (ISBN-0-19-512444-8) 1999 We have jurisdiction under 35 U.S.C. § 134(a). 1 Claims on appeal 2 Claims 6 and 9 are on appeal. Brief, page 2; Answer, pages 3 and 5. 3 Claim 6, which we reproduce from pages 17-18 of the Claim Appendix of 4 the Brief, reads [matter in brackets and indentation added; principal limitations in 5 issue in italics]: 6 Claim 6 7 A melt spun staple fiber having a circular or tetra lobal 8 cross-section made from a resin composition containing 9 [1] PTT [polytrimethylene terephthalate] homogenously 10 blended with 11 [2] dicarboxylic acid containing coPET [CoPolyester of 12 polyethylene terephthalate], 13 said dicarboxylic acid being at least one selected from a group 14 consisting of oxalic acid, malonic acid, succinic acid, glutaric acid, 15 adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, 16 1,10-decanedicarboxylic acid, isophthalic acid, sulfoisophthalic acid, 17 phthalic acid, naphthalenedicarboxylic acid, and diphenyl ether 18 dicarboxylic acid, 19 wherein the ratio of PTT : coPET is in the range of 80 : 20 to 20 30 : 70, 21 Appeal 2012-000438 Application 11/986,908 4 the intrinsic viscosities of coPET and PTT being in the ranges 1 of 0.5 to 0.70 and 0.5 to 1.40 respectively. 2 PTT is also referred to by those skilled in the art as (1) polypropylene 3 terephthalate or (2) 3-GT. Johnson ¶ 0041. 4 The rejection 5 While several rejections were made in the Final Rejection, only one 6 rejection is maintained in the Answer. 7 Claims 6 and 9 stand rejected as being unpatentable under § 103(a) over 8 Iohara and Johnson. 9 Analysis 10 Following a procedure suggested in Ex parte Braeken, 54 USPQ2d 1110, 11 1111 (BPAI 1999), the subject matter of Claim 6 is described as follows: 12 A melt spun {col. 5:20; col. 8:35} staple fiber {col. 8:37} 13 having a circular or tetra lobal cross-section {cross-section not 14 described} made from a resin composition containing 15 [1] PTT [polytrimethylene terephthalate] {Example 3 16 describes use of polytetramethylene terephthalate [PBT], but 17 polytrimethyl terephthalate is described at col. 5:2} homogenously 18 blended {col. 7:65} with 19 [2] dicarboxylic acid containing coPET [CoPolyester of 20 polyethylene terephthalate] {not described}, 21 said dicarboxylic acid being at least one selected from a group 22 consisting of oxalic acid, malonic acid, succinic acid, glutaric acid, 23 adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, 24 Appeal 2012-000438 Application 11/986,908 5 1,10-decanedicarboxylic acid, isophthalic acid, sulfoisophthalic acid, 1 phthalic acid, naphthalenedicarboxylic acid, and diphenyl ether 2 dicarboxylic acid {not described}, 3 wherein the ratio of PTT : coPET is in the range of 80 : 20 to 4 30 : 70 {col. 7:66-68}, 5 the intrinsic viscosities of coPET and PTT being in the ranges 6 of 0.5 to 0.70 {viscosity of PET described as 0.86; col. 8:28} and 0.5 7 to 1.40 {viscosity of PBT described as 0.86; col. 8:27} respectively. 8 The differences between the subject matter of Claim 6 and Iohara are: 9 (1) Iohara does not describe a tetra lobal cross-section; 10 (2) Iohara does not describe use of a coPET. 11 Applicant seems to agree. Brief, page 11 (“Iohara does not teach the cross 12 section or that the PET is copolymerized with the claimed dicarboxylic acids.”). 13 A Braeken analysis of Claim 6 vis-à-vis Johnson is as follows: 14 A melt spun {¶ 0015} staple fiber having a circular or tetra 15 lobal {¶ 0032, preferably 3-8 lobes; Fig. 12, illustrating tetra lobal 16 (¶ 0113; Table X-1 (page 19))} cross-section made from a resin 17 composition containing 18 [1] PTT [polytrimethylene terephthalate] {¶ 0041 described 19 as polypropylene terephthalate or 3-GT} homogenously blended 20 {¶ 0042 describing “bicomponent filaments”} with 21 [2] dicarboxylic acid containing coPET [CoPolyester of 22 polyethylene terephthalate], {¶ 0042 describing a copolymer of PET 23 made with a comonomer} 24 Appeal 2012-000438 Application 11/986,908 6 said dicarboxylic acid being at least one selected from a group 1 consisting of oxalic acid, malonic acid, succinic acid {¶ 0042—2 butanedioic acid}, glutaric acid {¶ 0042—pentanedioic}, adipic acid 3 {¶ 0042—hexanedioic acid}, pimelic acid, suberic acid, azelaic acid, 4 sebacic acid, 1,10-decanedicarboxylic acid, isophthalic acid {¶ 0042}, 5 sulfoisophthalic acid, phthalic acid, naphthalenedicarboxylic acid 6 {¶ 0042}, and diphenyl ether dicarboxylic acid, 7 wherein the ratio of PTT : coPET is in the range of 80 : 20 to 8 30 : 70 {¶ 0042—preferably about 70:30 to 30:70}, 9 the intrinsic viscosities of coPET and PTT being in the ranges 10 of 0.5 to 0.70 and 0.5 to 1.40 respectively {not explicitly described, 11 but relative viscosity is mentioned—¶¶ 0071; 0079; 0093} 12 Johnson appears to differ from the subject matter of Claim 6 in that Johnson 13 does not explicitly described the claimed intrinsic viscosities. Rather, Johnson 14 describes viscosities in terms of relative viscosities. See Stevens for a brief 15 discussion of relative viscosity and intrinsic viscosity. 16 Whether one views the evidence from a point of view of using the Johnson 17 PTT and coPET in place of the Iohara polymers or using polymers having the 18 intrinsic viscosities described by Iohara as polymers in the Johnson process, the 19 result is the same. The claimed subject matter on this record would have been 20 obvious to a person having ordinary skill in the art. Applicant is using known 21 materials for their intended purpose to make fibers and yarn. 22 The essential difference between Claim 6 (and Claim 9 for that matter) and 23 Johnson is a lack of an explicit description in Johnson of the claimed intrinsic 24 Appeal 2012-000438 Application 11/986,908 7 viscosities. Certainly Iohara establishes that it is known to use of a blend of 1 (1) polytetramethylene terephthalate having the claimed PTT intrinsic viscosity 2 and (2) PET (albeit not coPET) having the claimed intrinsic viscosity. 3 Applicant maintains that Iohara “teaches away” from the claimed invention. 4 Brief, page 12. According to applicant, the invention is said to obviate processing 5 difficulties said to arise out of different physicochemical properties of the 6 polymers. No method of making or using the claimed compositions is before us. 7 Nor, as observed by the Examiner, is any property recited in the claims. Answer, 8 page 9. Thus, on this record, applicant has not shown that the result alleged to 9 have been achieved by the compositions, as broadly claimed, is in fact obtained. 10 In re Klosak, 455 F.2d 1077, 1080 (CCPA 1972) (inventor must show that the 11 results the inventor says the inventor gets with the invention are actually obtained 12 with the invention). See also McClain v. Ortmayer, 141 U.S. 419, 429 (1891) 13 (conclusive evidence needed to establish new function). The “results” must be 14 commensurate in scope with the breadth of the claims. 15 Considerable discussion appears in the Brief and the Reply Brief concerning 16 objectives sought by Iohara. From our perspective, the relevant teaching of Iohara 17 is its intrinsic viscosities—the apparent point of difference between Johnson and 18 the claims on appeal. From a practical point of view, the USPTO is in no position 19 to determine whether relative viscosities of Johnson are the same as the intrinsic 20 viscosities of Iohara. However, one skilled in the art attempting to succeed in 21 using the Johnson process would necessarily seek to use polymers having suitable 22 viscosities. Broadly speaking, the Iohara polymers and the Johnson polymers are 23 used for the same general purpose, viz., to make filaments and yarns. On that 24 Appeal 2012-000438 Application 11/986,908 8 basis, it would appear that use of polymers with appropriate viscosities is within 1 the skill of the art. Applicable precedent holds that a reference may be said to 2 teach away when a person of ordinary skill, upon reading the reference, would be 3 discouraged from following the path set out in the reference. See In re Fulton, 4 391 F.3d 1195, 1201 (Fed. Cir. 2004), cited by the Examiner. Answer, page 8. 5 See also United States v. Adams, 383 U.S. 39, 52 (1966). We perceive no reason 6 why one skilled in the art would not be informed by the intrinsic viscosity 7 disclosure of Iohara as to suitable intrinsic viscosities of polymers to be used in the 8 Johnson process. 9 Iohara is said to teach use of “multiple components” for forming a fiber, 10 whereas the claimed invention is said to use a “blend.” Brief, page 13. Iohara 11 Example 3, however, explicitly mentions “blending” PET with PBT. In the Reply 12 Brief (page 2), applicant maintains that its “homogenized blend . . . acts as a single 13 polymer . . . .” Cited in support of the argument is Tammaji, ¶ 0075 (same as 14 Specification, page 11, paragraph bridging pages 11-12). It is not apparent why 15 the Example 3 blend of Iohara does not act as a single polymer. Based on the 16 Iohara teaching in combination with the Johnson bicomponent filaments, it would 17 be apparent to one skilled in the art that blends and bicomponent filaments are 18 viable alternatives. Moreover, if both PTT and coPET are known polymers for 19 making filaments, then it is not apparent why one skilled in the art would not have 20 used a blend of PTT and coPET to make a filament. It is generally prima facie 21 obvious to combine two compositions each of which is taught by the prior art to be 22 useful for the same purpose in order to form a third composition which is also used 23 for that purpose. See In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980), 24 Appeal 2012-000438 Application 11/986,908 9 reaffirming a long-standing principle of law, In re Crockett, 279 F.2d 274, 276 1 (CCPA 1960). 2 Iohara is said to be different in “texture”. Brief (page 14). No limitation in 3 Claims 6 or 9 would bring out that difference. 4 Applicant argues that Iohara does not describe the tetra lobal or coPET 5 features of the claimed invention. Those features are more than adequately 6 described by Johnson. 7 Other arguments 8 We have considered applicant’s remaining arguments and find none that 9 warrant reversal of the Examiner’s rejection. Cf. In re Antor Media Corp., 689 10 F.3d 1282, 1294 (Fed. Cir. 2012). 11 Decision 12 Upon consideration of the appeal, and for the reasons given herein, it is 13 ORDERED that the decision of the Examiner rejecting Claims 6 and 14 9 over the prior art is affirmed. 15 FURTHER ORDERED that no time period for taking any 16 subsequent action in connection with this appeal may be extended under 37 C.F.R. 17 § 1.136(a)(1)(iv). 18 AFFIRMED 19 20 bar 21 THIRD EDITION POLYMER CHEMISTRY AN INTRODUCTION Ma.lcolm P. Stevens University of Hartford New York Oxford OXFORD UNIVERSITY PRESS 1999 Oxford University Press Oxford New York Athens Auckland Bangkok Bogota Buenos Aires Calcutta Cape Town Chennai Dar es Salaam Delhi Florence Hong Kong Istanbul Karachi Kuala Lumpur Madrid Melbourne Mexico City Mumbai Nairobi Paris Sao Paulo Singapore Taipei Tokyo Toronto Warsaw and associated companies in Berlin lbadan Copyright © 1999 by Oxford University Press, Inc. Published by Oxford University Press, Inc. 198 Madison Avenue, New York, New York 10016 http://www.oup-usa.org Oxford is a registered trademark of Oxford University Press All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic. mechanical, photocopying, recording. or otherwise, without the prior permisssion of Oxford University Press. Library of Congress Cataloging-in.Publication Data Stevens. Malcolm P., 1934 Polymer chemistry: an introduction I Malcolm P. Stevens. - 3rd ed. p. cm. Includes bibliographical references and index_ ISBN 0-19-512444-8 (hardcover) 1. Polymers. 2_ Polymerization. I. Title. QD381.S73 1999 98-23083 547' .7--<1c21 CIP Printing (last digit): 9 Printed in the United States of America on acid-free paper. 50 Polymer Structure and Properties between 10,000 and 10,000,000. Older light-scattering photometers employed high-pressure mercury lamps and filters to obtain a monochromatic beam. These have been supplanted with laser light sources. A schematic of a laser light-scattering photometer is given in Figure 2.7. 2.4.2 Ultracentrifugation The ultracentrifuge is by far the most intricate and expensive instrument for determining mo lecular weight.ge,18,19a It is not as widely used as light scattering or osmometry in determin ing molecular weights of synthetic polymers, but it has been used extensively with natural polymers, particularly proteins, and it is useful for determining M z of synthetic polymers. The technique is based on the principle that molecules, under the influence of a strong cen trifugal field, distribute themselves according to size perpendicularly to the axis of rotation, a process called sedimentation, the rate of which is proportional to molecular mass. Centri fugation is accomplished in an evacuated chamber in a cell set in a rotor, both of which are provided with windows so that optical methods, such as index of refraction measurements or interferometry, can be used to observe concentration gradients within the polymer solu tion. Details of the technique may be found in the references provided. 2.5 Viscometry Measurements of dilute solution viscosity provide the simplest and most widely used tech nique for routinely determining molecular weights.9f,19b It is not an absolute method; each polymer system must first be calibrated with absolute molecular weight determinations (usu ally by light scattering) run on fractionated polymer samples. Viscosities are measured at concentrations of about 0.5 gllOO mL of solvent by determining the flow time of a certain volume of solution through a capillary of fixed length. Flow time in seconds is recorded as I f 1 ~i· "_ 10k" f~ ~{~ "'" :!~ i' l<~' C A B FIGURE 2.8. Capillary viscometers: (A) Ubbelohde, and (B) Cannon-Fenske. TABLE Com, Relati Specil R.edt!~ Inhen Int:ri:Q 'Cane theti are r n1<;>t1 tam, vptr I the the i with mel" mat ent by 1 wet, co!;; Cfp,J; I GOS i to"·~ IF]I:ll tl~ ( Pt~ saD vet incl I gr~ Molecular Weight and Polymer Solutions 51 re :h 7. TABLE 2.2. Dilute Solution Viscosity Designationsa Common Name lUPAC Name Definition Relative viscosity Viscosity ratio _ 11 _ 11rel - - 110 t to ) t Specific viscosity 11sp=~ 110 to 11rel Il >. t, Reduced viscosity inherent viscosity Viscosity number Logarithmic viscosity number ." _ ',red - 11inh ~ __11",re,,-t__' C - C In 11rel C e s Intrinsic viscosity Limiting viscosity number [11] = (~) = \ C c=o (11inh)C = 0 'Concentratlons (most commonly expressed in grams per 100 mL of solvent) of aboLIt 0.5 g/dL the time for the meniscus to pass between two designated marks on the viscometer. Viscosities are run at constant temperature, usually 30.0 :.t 0.01°C. Two typical viscometers are shown in Figure 2.8. Of the two, the Ubbelohde type is more convenient to use in that it is not necessary to have exact volumes of solution to ob tain reproducible results. Furthermore, additional solvent can be added (assuming the reser voir is large enough); thus concentration can be reduced without having to empty and refill the viscometer. Whichever type is used, it is necessary to filter the polymer solutions into the viscometer because dust particles affect flow time. Filtration is conveniently accomplished with micro filter attachments to syringes. Computer-driven viscometer modules are com mercially available. They measure capillary flow time photoelectrically and provide auto matic dilution and mixing as well as calculation and read-out of viscosity. Viscosity can be expressed in several ways (Table 2.2). Common names are, at the pres enttime, more widely used than the IUPAC-recommended2o names. (The latter were adopted by the IUPAC to avoid inconsistencies arising from "viscosity" designations where there were no units of viscosity.) Relative viscosity (viscosity ratio) (71rel) is the ratio of solution viscosity to solvent vis cosity, which is proportional to a fIrst approximation for dilute solutions to the ratio of the cor responding flow times. Viscosity units (commonly expressed as poises) or flow times cancel out in the various viscosity expressions. Specific viscosity (71sp) is the fractional increase in vis cosity. Both 71rel and 71sp are dimensionless. As concentration increases, so does viscosity. Hence to eliminate concentration effects, the specifIc viscosity is divided by concentration and ex trapolated to zero concentration to give the intrinsic viscosity, [71]. Not uncommonly viscosi ties are determined at a single concentration and the inherent viscosity (71inh) is used as an ap proximate indication of molecular weight. Inherent and reduced viscosities extrapolate to the same intrinsic viscosity at zero concentration. Concentration, C, is in grams per 100 mL of sol vent or in grams per cubic centimeter, more commonly the former. Thus reduced, inherent, and intrinsic viscosities have units of deciliters per gram or, less commonly, cubic centimeters per gram. Obviously, units of concentration must be specifIed when viscosity data are reported. 52 Polymer Structure and Properties Intrinsic viscosity is the most useful of the various viscosity designations because it can be related to molecular weight by the Mark-Houwink-Sakurada equation: [11] = KMya where My, is the viscosity average molecular weight, defined as _ (W.M.l+G)l/aM = II v 'iNiMi Log K and a are the intercept and slope, respectively, of a plot of log (11J versus log Mw or log Mn of a series of fractionated polymer samples. Such plots are linear (except at low mo lecular weights) for linear polymers, thus 10g[11] = log K + a log M TABLE 2.3. Representative Viscosity-Molecular Weight Constantsa Polymer Solvent Polystyrene (atactic)C Polyethylene (low pressure) Poly(vinyl chloride) Polybutadiene 98% cis-lA, 2% 1,2 97% trans-lA, 3% 1,2 Polyacry\onitri\e Poly(methyl methacrylate co-styrene) 30-70 mol % 71-29 mol % Poly( ethylene terephthalate) Nylon 66 "Values taken from Ref. 4e. Cyclohexane Cyclohexane Benzene Decalin Benzyl alcohol Cyclohexanone Toluene Toluene DMFg DMF l-Chlorobutane I-Chlorobutane m-Cresol m-Cresol bSee text for explanation of these constants. CAtactic defined in Chapter 3. dO temperature. ·Weight average. fNumber average. g NN-dimethylformamide. Temperature. Molecular Weight °C Range X 10-4 35d 50 25 135 155.4d 20 30 30 25 25 30 30 25 25 8-42e 4-137e 3--61 f 3-1ooe 4-35e 7-13 f 5-50f 5-16f 5-27e 3-100f 5-55° 4.8--8Ie O.D4-1.2f 1.4-5f Kb X 103 ab 80 26.9 9.52 0.74 67.7 0.67 156 0.50 13.7 1.0 30.5 0.725 29.4 0.753 16.6 0.81 39.2 0.75 17.6 0.67 24.9 0.63 0.77 0.95 240 0.61 ~.--~~---- Alsetl . .1 tIg~¢\ niqUlj 8ep1:t\ fuep\ ing. ,( cules. Molecular Weight and Polymer Solutions 53 Viscosity average molecular weights lie between those of the corresponding Mwand Mn, an but closer to the former. Hence better results are obtained if K and a are determined with fractionated samples of measured Mw. To evaluate K and a requires considerable manipula tion, but fortunately a wide range of values representing a broad spectrum of polymers, sol vents, and temperatures has been published.4e For most common polymers, values of a vary between 0.5 (for a randomly coiled polymer in a theta solvent) and 0.8; for more rodlike extended-chain polymers where the hydrodynamic volume is relatively large, a may be as high as 1.0, in which case Mv = Mw. K values generally vary between 10-3 and 0.5. A few representative values of a and K are given in Table 2.3. or Factors that may complicate the application of the Mark-Houwink-Sakurada relation 10- ship are chain branching, too broad a molecular weight distribution in the samples used to determine K and a, solvation of polymer molecules, and the presence of alternating or block sequences in the polymer backbone. Chain entanglement is not usually a problem at such high dilution unless molecular weights are extremely large. Other types of viscosity measurements based on the principle of mechanical shearing19b are also employed, most commonly with concentrated polymer solutions or undiluted poly mer; these methods, however, are more applicable to flow properties of polymers (Chapter 3), not molecular weight determinations. Relative methods of determining molecular weight on the basis of polymer fractionation are discussed in the next section . . 50 2.6 Molecular Weight Distribution .599 .74 Molecular weight distribution is an important characteristic of polymers because it can sig .67 nificantly affect polymer properties. Just as low-molecular-weight polystyrene behaves dif ferently from the high-molecular-weight material, a sample of polystyrene having a narrow .50 molecular weight range will exhibit different properties from one having a broad range, even .0 if the average molecular weights of the two samples are the same. The relatively new mass spectrometric methods for determining molecular weight were 1.725 described earlier in Section 2.3.5. As may be seen from Figure 2.5, the molecular weight 1.753 1.81 distribution is also apparent in the mass spectrum. Molecular weight distribution may also ).75 be obtained by ultracentrifugation. More widely used techniques for determining molecular weight distribution involve fractionation of the polymer sample and comparison of the frac tions thus obtained with samples of known absolute molecular weight by means of some cal 167 ibration procedure. A variety of fractionation methods have been developed. J.63 ),95 2.6.1 Gel Permeation Chromatography (GPC) 161 Also called size exclusion chromatography (SEC), GPc9g,21,22a is by far the most widely used method of determining molecular weight distribution. A column chromatography tech nique, GPC may be used preparatively to obtain narrow molecular weight fractions. Separation is accomplished on a column packed with a highly porous material that separates the polymer molecules according to size, a phenomenon often referred to as molecular siev ing. Current thinking is that separation is based on the hydrodynamic volume of the mole cules rather than on the molecular weight per se.23 Small molecules are able to diffuse into Copy with citationCopy as parenthetical citation