|Publication number||US2008526 A|
|Publication date||16 Jul 1935|
|Filing date||3 Nov 1932|
|Priority date||3 Nov 1932|
|Publication number||US 2008526 A, US 2008526A, US-A-2008526, US2008526 A, US2008526A|
|Inventors||Charles Wappler Frederick, Wappler Frederick C|
|Original Assignee||Charles Wappler Frederick, Wappler Frederick C|
|Export Citation||BiBTeX, EndNote, RefMan|
|Referenced by (66), Classifications (6)|
|External Links: USPTO, USPTO Assignment, Espacenet|
July 16, 1935 R. H. WAPPLER ET AL METHOD AND MEANS FOR TREATING LIVING TISSUE Filed Nov 3 32 Patented July 16, I935 METHOD AND- MEANSFOR TREATING LIVING TESSUE Reinhold H. Warbl r, Yonk rs, and Fr d r k Charles Wapplen'New York, N. Y; Frederick C. Wal plcr executor of said Reinhold H.
Wappler, deceased Application November 3, 1932, Serial No. 640,972
7 8 Claims. (Cl. 174 89 Q Our present invention relates generally EQthe art of treating living tissue, and has particular reference to a new mode 013 treatmenh-eoordh n ly, o a n w and improve ins rument.
5 o I i a n r l o je t of our inv n ion to p o: vide anew method of heat treating tissue for the g er l p rp se of all viatin pro rusi ns or abnormal swellings or growths; and it is a particular object of our invention to provide a mo e of 10 r a m which i 'essentially nonsur ical and which is largely predicated upon'the ability oi the body itself, dur ng its natural ,function nato absorb or digest properly de-vitalizcd'matter,
Our present method and inst ument inv lves the employment of high-irequency electric cur rents of the g neral char ct r which haveire cently p ove hemselves to be remarkably emcacious in producing a variety of efiects. For e' x. ample, a sustained high-frequency current of'the character which is produced by an electrical generating pparatus of. t eneral type illus-. trated and described in the copcnding application of Frederick Charles Wappler, Serial Number 581.9528, is suitable for our present purposes. i
It is well known that the passage of small amounts of high frequency current through body tissue will produce a pure non-surgical diathermic effect which consists essentially ingently warm-l ing the tissue. Such treatment stimulates not only the flow of blood and lymph, but also the n ral vity of he tissue cells and is a widely accredited mode of treating living tissue for the purpose of producing certain well-recognized therapeutic effects.
Where a greater amount of current is ems ployed, the cheat of its passage through living tissue has been found to produce what has come to be known as coagulation, whereby an actual cooking of the tissue-is. effected, resulting not only in destruction of tissue cells and. "blood vessels and the like, but also in actual coagulation and dehydration of blood and lymph. This mode of treatment is of a valuable character; for example, in effecting hemostasis, during the p'er+ .formance of surgieal operations; andit has also been resorted to, with more or less success, in the alleviation of protrusions and similar masses. Its employment is, however, necessarilyaccompa d by t p duction of dead tissue or matter which must be immediately excised, resected; or withdrawn, especially where such masses of dead matter are produced in large quantities. Relatively smaller areas of coagulatecl areas are readily sloughed by the body, and irequently with-p. out any injurious results, but this acticnls in,
herently dangerous and is akin to actual excision, as distinguished from normal absorption by the body itself..
With still greater quantities of current, a cutting effect is produced which has proven to be of extreme value in the performance of a number of surgical operations,
Our present invention is predicated upon the discovery that the employment of a high-frequency current of the character mentioned, in
concentrations greater than those which produce may be accomplished without resorting to any excision or relying upon sloughing of dead matter. Furthermorcythe effects produced are somewhat akin to coagulationin so far as a certain devitaliza-tion of cells seems to be accomplished, but the effects a e en ir y d fferent and distinct from coagulation in that the liquid state of. the blood and lymph remains utterly unimpaired.
The present elfects first manifest themselves under current concentrations of the order of two milliazmperes per square millimeter, and appear to be most advantageously produced at approximately four milliamperes per square millimeter. Ordinary .mild coagulation as the same isv now practiced in the art is not capable of accomplishment under concentration less than approximately 51X milliamperes per square millimeter.
The resent mode of procedure, and the eifects produced thereby, have been termed by us, for lack of a better designation, as non-destructive shrinkage, and consist apparently, in a devitalization of tissue cells sufilcient to interrupt and disorganize the normal activities of such cells, coupled with a stimulation; of the normal flow of blood and lymph. The importance of this result will be'obvious, inasmuch as it is the normal blood and lymph'fiowwhich lies at the basis of natural absorption by the body itself. From the standpoint of blood and lymph flow, the present effect is apparently new and valuable because of the fact that thevcell activities are not simultaneouslyvstimulated but are, on the contrary, disrupted; and-fromthe standpoint of disorgani .zation and devita'lization of cells, the present systems of blood and lymph which feed the cells in question.
The present effect distinguishes further from ordinary well known coagulation in that the nor- 7 mal coagulative treatment is cumulative in. its effect. As more and more tissue becomes coagulated, it becomes more and more non-conductive, and the corresponding increase in resistance produces more and more coagulation and dehydration. The present type of treatment of tissue is not cumulative and is, in this respect, similar to ordinary non-surgical diathermy. The time factor in the present case increases the penetration of the effect at a rate of approximately onefourth inch per minute, but is not accompanied by any increase in current concentration through the tissue subjected to the treatment. Apparently the present procedure results from the generation of a heat which is sufiicient t devitalize and disorganize cells and cell activities, yet illslllfiClillt'tO' impair the normal liquidity of the bloodand lymph. This immunity of the latterfluids may perhaps be due to the cooling effect of the latter upon the walls of the vessels and capillaries through which these fluids flow. Thefeffect of our present modeof treatment liesin'a recession or shrinkage of the areas or masses'wl'iich are subjected tothe passage of the current, as hereinbefore described, and most of this shrinkage takes place after the treatment has been completed, as a-result of which we have been led to the conclusion that the recession is a normal one, resulting from the natural fun'c tioning of the circulatory systems of the body in absorbing or digesting the cells which have been suitably devitalized. The treatment is accom-' panied by no rise in temperature nor in any other discomfort or undesired reaction.
The instrument which we prefer to employ in carrying out the present procedure is one of relative simplicity and is simple to manufacture, control, and manipulate. It consists essentially of an electrode member which is tubular in char-, acter and which is provided with a wall portion Means are provided for constantly subjecting the interior of the electrode member to the cooling action of water or thelike, whereby the operative electrode surface is kept in a cool condition and whereby surface dehydration of the tissue being treated is reduced to a minimum.
We achieve the foregoing objects, and such other objects as may hereinafter appear or be pointed out, in the manner illustratively exemplified in the accompanying drawing, wherein-- Figure l is a side'elevational View of an instrumerit constructed in accordance with our present invention; V a
Figure 2 is a similar view, on an enlarged scale, with portions shown injcross-section;
FigureB is a View taken from the bottom of Figure 2, showing the operative end of the instrument in one relationship of parts;
Figure 4 is a view similar to Figure 3, showing a different relationship of parts;
Figure 5 is a cross-sectional view taken substantially along the line .55 of Figure 2,.with certain pieces of mechanism omitted for the sake of clearness; and a Figure 6 is a View similar to Figure 5, with th parts in the relationship shown in Figure 4.
The endoscopic tube or sheath I0 is composed of insulating material, and is laterally fenestrated at its forward end, as at I I. It terminates at its rear end in a collar I2, also preferably of insulating material, and with the receptive rear neck I3 'into which the operative portions of the instrument are adapted to be inserted.
Carried by the neck I3 is the irrigation outlet tube I4, as well as the block I5 which serves to facilitate theattachment of the interior elements. The block I5 is preferably provided with a clamp ing device I6 which may be of any conventional or desired character. I
The unit which is adapted'to be inserted-into the neck I3 consists of the tubular element I! with a forward attenuated portion I8 adapted to be inserted into a wedged relationship with the neck I3. During this association oifparts the fork I 9 is adapted to engage around the block I5, and the clamping device I6 is adapted to contact with or engage one or more pins .26 provided on this fork, inthe conventional manner.
' At the rear end of. the element H, the latter is interiorly threaded and is adapted to receive the ferrule'member- 2|. This member carries the irrigation inlet conduit 22, the latter communicating with the longitudinally'arranged conduit 23 which extends'forwardly well into the body of the sheath I 0, as will be presently described in greater detail.
The ferrule member 2| also carries the rearwardly extending tubular guide 24 through which a suitable telescope is adapted to be inserted'and accommodated, the usual clamping device 25 be The'telescope which we prefer'to employ is constructed substantially like that illustrated and described in Letters Patent No. 1,680,491, and con sists preferably of an elongated tube having a suitable eyepiece 26 at the rear end, an objective lens 21 near the forward end, and a lamp 28 scope and hold itin fixed relationship to the conduit 23.
On the interior of the element I I we provide an annular recess or groove in which a coilar BI is rotatably mounted. The collar carries the ra" dially'projecting handle 32 which extends on"- wardly through an arcuate slot in the element" I 1. This slot extends through approximately 180 so that the handle 32 may be rotated from the full-lineposition of Figures 1 and 2 to the dotthe collar 3I through approximately-180.
Carried by the collar 31 is the presentitype of electrode member which is composed of a me; tallic tube 33 extending forwardly in snug yet rotatable relationship with respect to the sheath 1.0. It is to be noted that this tube encompasses the conduit .23 and the telescope 24. Accordingly, although the telescope and the conduit 23 are ar ranged within the tubular electrode member 33, the latter may be rotated with respect to these elements, and with respect to the sheath it, by virtue of the fact that the telescope and the duit 23 are secured to the s cat 1 through i intermediary of the ferrule 2i and the element ii.
At the forward end of theelectrode member 33, the latter is provided with a closed and rounded end or tip 34 which is of insulating material. This tip extends somewhat beyondthe forward end of the sheath 10, so that when the entire as sembly is inserted into a body cavity the forward edge of the sheath It! will not impair the ease with which this may be accomplished.
Slightly to the rear of the tip 34, the electrode member 33 is provided with a wall portion 35 (Figures 4 and 6) which is adapted to serve as an operative surface for establishing contact with the tissue to be treated. This wall portion is preferably provided with the relatively small and narrow slit 35. The opposite wall portion is cut away to provide the relatively large opening 37.
The various parts are so mounted that the rotatability of the tubular member 33 within the sheath it permits either the operative surface 35 or the opposite opening 57 to be selectively positioned in registry with the fenestra ii of the sheath i0. Furthermore, the telescope 2-4 is so mounted that it constantly commands-a field of vision through the fenestra H. Accordingly, when the tubular electrode member is rotated into the position of Figures 2, 3, and 5, the telescope commands an unobstructed illuminated field of vision through the opening 3? and, the fenestra' ll. When the member 33 is rotated through 180, the operative surface 35 is exposed through the fenestra H, but a certain degree of visibility is still achieved through the slit 35.
In either of the extreme positions of the member 33, the flow of irrigating liquid is unimpeded by virtue of the fact that apair of openings 38 are arranged in the tube in opposite walls thereof, in alignment with the outlet 14.
All of the parts, except the tip 34, the sheath iii, and the collar !2, may be composed of conductive material and are preferably composed of metal. The-element ll alsocarries electric terminal 39 which is thus electrically connected with the tube 33 and hence with the operative surface 35, and which is adapted to be connected to a suitable source of high-frequency current.
When the instrument is employed, it is first inserted into the desired body cavity with the parts in the relationship of Figures 1, 2, 3, and 5. Complete illuminating visibility is thus maintained, until the desired area, usually a protrusion, is properly located and positioned within the fenestra H. The handle 32 is then rotated through 180, thereby swinging the member 33 into the relationship of Figures 4 and 6, and
thereby positioning the operative surface in direct contact with the area of tissue to be treated. Constant irrigation may be maintained through the inlet 22, thence through the conduit 23, to the operative area, thence rearwardly through the tubular member 33, and out of the outlet l4.
With suitable electrical connection made to the terminal 39, and with a corresponding suitable connection between an indifierent electrode and a relatively remote portion of the body being treated, high-frequency electric current may be caused to pass through the tissue area which is contacted by the surface 35. The area may, to a certain degree, be kept under visibility by virtue of the slit 35., althoughit will be understood that the instrument must be rotated slightly inorder to bring into visionthe tissue that has been in contact with the surface 35.
The current which we employ has a concentratreatment, Thus, for a desired depth of penetra tion of the present effect, a known current -concentration throughout-the known contact area of the operative surface 35 can be definitely caused to produce the desiredeffect in a calculated and predetermined period of time, 1
As hereinbefcre stated, the treatment is not accompanied by any coagulation or destruction of tissue, as the same is ordinarily recognized or thought of. The surface under treatment usually undergoes a slight blanching in appearance, but there is very little surface dehydration (this is reduced to an absolute minimum by the cooling effect of the irrigation liquid), and there is no cumulative penetration of any coagulating effect. Accordingly, the'treatment is not accompanied by the formation of any dead mass which must be excised or which will ultimately be sloughed.
The enects-of'the treatment, after a -period of aday or so, are, however, truly remarkable inasmuoh as a substantial recession or shrinkage of.
the tissue inevitably manifests itself. This,,we conclude, is due to a natural absorption by a stimulated blood and lymph circulatory system, of cells which have been sufficiently disorganized and devitalized to permit themselves to be absorbed. This shrinkage or recession isaccompanied by a normal degree of recession of capillaries and the like, as in allnatural casesof absorption. 1
While our method and mode of treatment has a wide varietyof applications in the art, and while wedo not claim the same as a meansfor treating or curing any particular ailments or diseases we will state that eminently satisfactory and remarkable results have been achieved in a variety of cases. In the case or", fibrous growths, whether benign or; malignant, the fibrous cells seem to be definitely disorganized, without any interruption, and, in fact, with a definite stimulation, of the circulatory systems feeding the same, with the result that marked shrinkages of such growths have been noted. Furthermore, it has been definitely ascertained that malignancy ceases in the areas that have been subjected to the treatmenhthereby confirming our conclusion that the cell activities have become disorganized.
Similar desirable results have been achieved in the alleviation of prostate gland enlargements or swellings, in connection with shrinkage of tonsilsvand'the like, in the treatment of various rectal troubles, and in hypertrophles and pro trusions in general, or any neoplasm, wherever situated.
Whatever the purpose oi the treatment may I beyit is apparent to us that an entirely new technique has been developed with far-reaching possibilities; and the essential characteristic of the treatment, without regard to the particular tissue whichis sought to be shrunk, or to the particular purposesior which such shrinkage may be sought,lies in heat treating the tissue, by the passage of a high-frequency current of critical concentration, to: a degree sufilcient to devitalize tissue cells yet insufficient to impair the normal blood and lymph circulatory systems fore intended that these details beinterpreted as illustrative, and not in a limiting sense.
Having thusdescribed our invention, and illustrated its use, what we claim as new and desireto secure by Letters Patent is-- l. The herein-described method of shrinking living tissue, which consists in heating the same to a degree sufiicient to devitalize the tissue cells but insuiiicient to impair the liquid state of the blood and lymph, whereby, the blood and lymph flow are stimulated and the devitalized cells may be promptly absorbed.
2. The herein-described method of shrinking living tissue, which consists in passing there through a high-frequency electric current whose concentration is just sufiicient to effect devitalization of the tissue cells but insufiicient'to coagulate the blood and lymph, whereby the devitalized cells may be promptly absorbed.
3. Theherein described method of shrinking living tissue, which consists in passing therethrough a high-frequency electric current whose concentration is within the range of approximately two to six milli-amperes per squaremfllimeter, such concentration being sufiicient to devitalize tissue cells but insuflicient toimpair the liquid state of blood and lymph.
4. The herein-described method of shrinking living tissue, which consists in passing therethrough a high-frequencyelectric current whose, concentration is approximately four milli-amperes per square millimeter.
5. In an instrument of the character described, a' tubular electrode member having a rounded and closed forward tipcomposed of insulating material, a wall portion just rearwardly oi the tip being of conductive materialand adapted to serve as an operative surface for contacting tissue to be treated, the opposite wall portion being cut away to provide arelatively large opening,
a laterally fenestrated endoscopicsheath enclosing said member, a telescope secured to said sheath and'arranged within the electrode mem ber to command a field of vision through said sheath ienestra, and means .for rotating the electrode member relative to said sheath to se lectively position the'operative surface or the opposite opening in registry with said fenestra.
6. In an instrument of the character described, a tubular electrode member having a rounded and closed forward tip composed of insulating material, a wall portion just rearwardly of the tip being of conductive material and adapted to serve as an operative surface for contacting tissue to be treated, said wall portion having a relatively small'slit therein and the opposite wall portion being cut away to provide a relatively large opening, a laterally fenestrated endoscopic sheath enclosing said membena telescope secured to said sheath and arranged within the electrode member to command'a field of visionwall being cut away to provide a relatively large opening, a telescope mounted within said memher and adapted to command a forwardly oblique field of vision, and means for rotating the member relative to the telescope to bring either the operative surface or the opposite opening into registry with the field of vision. I
8. In an instrument of the characteridescribed a laterally fenestrated endoscopic tube of insulating material, a tubular metallic electrode member snugly yetrotatably'mounted therein andprovided with an apertured operative wall portion adapted to be rotated into registry with saidfenestr'a,'an electric terminal at the 'rear endof said electrode memberand adapted to be con: nected to a source of high-frequency current, and a telescope secured to said endoscopic tube and extending into the tubular electrode member so as to command an obliquely forward field of vision through said fenestra and hence through the aperture in said operative wall portion when
|Citing Patent||Filing date||Publication date||Applicant||Title|
|US2487502 *||26 Sep 1945||8 Nov 1949||American Cystoscope Makers Inc||Instrument for electrosurgical resection|
|US3850175 *||3 Jul 1972||26 Nov 1974||Lglesias J||Resectoscope with continuous irrigation|
|US3858586 *||1 Jun 1973||7 Jan 1975||Martin Lessen||Surgical method and electrode therefor|
|US4949732 *||24 Aug 1989||21 Aug 1990||Gyno Pharma Inc.||Apparatus for insertion and fixation of an intra uterine contraceptive device to the uterine fundus|
|US4955884 *||2 Jun 1988||11 Sep 1990||Circon Corporation||System for reducing drag on the movement of an electrode in a resectoscope|
|US5366490 *||22 Dec 1993||22 Nov 1994||Vidamed, Inc.||Medical probe device and method|
|US5370675 *||2 Feb 1993||6 Dec 1994||Vidamed, Inc.||Medical probe device and method|
|US5385544 *||14 May 1993||31 Jan 1995||Vidamed, Inc.||BPH ablation method and apparatus|
|US5409453 *||19 Aug 1993||25 Apr 1995||Vidamed, Inc.||Steerable medical probe with stylets|
|US5421819 *||13 May 1993||6 Jun 1995||Vidamed, Inc.||Medical probe device|
|US5435805 *||13 May 1993||25 Jul 1995||Vidamed, Inc.||Medical probe device with optical viewing capability|
|US5456662 *||9 May 1994||10 Oct 1995||Edwards; Stuart D.||Method for reducing snoring by RF ablation of the uvula|
|US5470308 *||19 Nov 1993||28 Nov 1995||Vidamed, Inc.||Medical probe with biopsy stylet|
|US5470309 *||12 Jan 1994||28 Nov 1995||Vidamed, Inc.||Medical ablation apparatus utilizing a heated stylet|
|US5514131 *||23 Sep 1994||7 May 1996||Stuart D. Edwards||Method for the ablation treatment of the uvula|
|US5531677 *||11 Apr 1995||2 Jul 1996||Vidamed, Inc.||Steerable medical probe with stylets|
|US5542915 *||12 Jan 1994||6 Aug 1996||Vidamed, Inc.||Thermal mapping catheter with ultrasound probe|
|US5554110 *||12 Jan 1994||10 Sep 1996||Vidamed, Inc.||Medical ablation apparatus|
|US5556377 *||22 Dec 1993||17 Sep 1996||Vidamed, Inc.||Medical probe apparatus with laser and/or microwave monolithic integrated circuit probe|
|US5599294 *||7 Oct 1994||4 Feb 1997||Vidamed, Inc.||Microwave probe device and method|
|US5599295 *||8 Nov 1995||4 Feb 1997||Vidamed, Inc.||Medical probe apparatus with enhanced RF, resistance heating, and microwave ablation capabilities|
|US5607389 *||27 Nov 1995||4 Mar 1997||Vidamed, Inc.||Medical probe with biopsy stylet|
|US5630794 *||23 Sep 1994||20 May 1997||Vidamed, Inc.||Catheter tip and method of manufacturing|
|US5672153 *||26 Sep 1994||30 Sep 1997||Vidamed, Inc.||Medical probe device and method|
|US5720718 *||6 Jan 1994||24 Feb 1998||Vidamed, Inc.||Medical probe apparatus with enhanced RF, resistance heating, and microwave ablation capabilities|
|US5720719 *||26 Sep 1994||24 Feb 1998||Vidamed, Inc.||Ablative catheter with conformable body|
|US5749846 *||7 Jun 1995||12 May 1998||Vidamed, Inc.||Medical probe device with optical viewing capability|
|US5762626 *||23 Aug 1996||9 Jun 1998||Vidamed, Inc.||Transurethral needle ablation device with cystoscope and method for treatment of the prostate|
|US5800378 *||20 Mar 1996||1 Sep 1998||Vidamed, Inc.||Medical probe device and method|
|US5807309 *||29 Jan 1997||15 Sep 1998||Vidamed, Inc.||Transurethral needle ablation device and method for the treatment of the prostate|
|US5843026 *||23 May 1996||1 Dec 1998||Vidamed, Inc.||BPH ablation method and apparatus|
|US5848986 *||21 Jun 1996||15 Dec 1998||Vidamed, Inc.||Medical probe with electrode guide for transurethral ablation|
|US5865788 *||23 May 1996||2 Feb 1999||Vidamed, Inc.||Self-contained power sypply and monitoring station for RF tissue ablation|
|US5871481 *||11 Apr 1997||16 Feb 1999||Vidamed, Inc.||Tissue ablation apparatus and method|
|US5873877 *||11 Apr 1997||23 Feb 1999||Vidamed, Inc.||Medical probe device with transparent distal extremity|
|US5895370 *||7 Jan 1997||20 Apr 1999||Vidamed, Inc.||Medical probe (with stylets) device|
|US5964727 *||24 Dec 1997||12 Oct 1999||Vidamed, Inc.||Medical probe device and method|
|US5964756 *||11 Apr 1997||12 Oct 1999||Vidamed, Inc.||Transurethral needle ablation device with replaceable stylet cartridge|
|US6022334 *||17 Apr 1998||8 Feb 2000||Vidamed, Inc.||Medical probe device with optic viewing capability|
|US6102886 *||27 May 1998||15 Aug 2000||Vidamed, Inc.||Steerable medical probe with stylets|
|US6129726 *||17 Mar 1999||10 Oct 2000||Vidamed, Inc.||Medical probe device and method|
|US6193714||23 Feb 1999||27 Feb 2001||Vidamed, Inc.||Medical probe device with transparent distal extremity|
|US6206847||17 Mar 1999||27 Mar 2001||Vidamed, Inc.||Medical probe device|
|US6241702||9 Jun 1998||5 Jun 2001||Vidamed, Inc.||Radio frequency ablation device for treatment of the prostate|
|US6419653||5 Feb 1998||16 Jul 2002||Vidamed, Inc.||Medical probe device and method|
|US6428503||18 Jan 2000||6 Aug 2002||Atc Technologies, Inc.||Surgical instrument for providing suction and irrigation|
|US6464661||27 Mar 2001||15 Oct 2002||Vidamed, Inc.||Medical probe with stylets|
|US6514247||8 Oct 1999||4 Feb 2003||Vidamed, Inc.||Transurethral needle ablation device with aligned handle|
|US6529775||16 Jan 2001||4 Mar 2003||Alsius Corporation||System and method employing indwelling RF catheter for systemic patient warming by application of dielectric heating|
|US6530946||3 Oct 2000||11 Mar 2003||Alsius Corporation||Indwelling heat exchange heat pipe catheter and method of using same|
|US6607529||19 Jun 1995||19 Aug 2003||Medtronic Vidamed, Inc.||Electrosurgical device|
|US6852091||15 Apr 2002||8 Feb 2005||Medtronic Vidamed, Inc.||Medical probe device and method|
|US7201731||20 Apr 2000||10 Apr 2007||Lundquist Ingemar H||Treatment device with guidable needle|
|US7387626||3 Aug 2004||17 Jun 2008||Medtronic Vidamed, Inc.||Medical probe device and method|
|US8980864||20 Dec 2013||17 Mar 2015||Moderna Therapeutics, Inc.||Compositions and methods of altering cholesterol levels|
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|US9061059||3 Feb 2014||23 Jun 2015||Moderna Therapeutics, Inc.||Modified polynucleotides for treating protein deficiency|
|US9089604||3 Feb 2014||28 Jul 2015||Moderna Therapeutics, Inc.||Modified polynucleotides for treating galactosylceramidase protein deficiency|
|US9095552||12 Dec 2013||4 Aug 2015||Moderna Therapeutics, Inc.||Modified polynucleotides encoding copper metabolism (MURR1) domain containing 1|
|US9107886||12 Dec 2013||18 Aug 2015||Moderna Therapeutics, Inc.||Modified polynucleotides encoding basic helix-loop-helix family member E41|
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|US9149506||16 Dec 2013||6 Oct 2015||Moderna Therapeutics, Inc.||Modified polynucleotides encoding septin-4|
|US9181319||6 May 2014||10 Nov 2015||Moderna Therapeutics, Inc.||Engineered nucleic acids and methods of use thereof|
|US9186372||21 May 2013||17 Nov 2015||Moderna Therapeutics, Inc.||Split dose administration|
|US20050010203 *||3 Aug 2004||13 Jan 2005||Medtronic Vidamed, Inc.||Medical probe device and method|
|U.S. Classification||600/104, 607/99, 606/49|