Full opinion text
OPINION AUGELLI, District Judge: This is an action for infringement of United States Letters Patent No. 2,563,-794 (’794 patent) and No. 2,703,302 (’302 patent). The subject matter is vitamin B-12 and vitamin B-12 active compositions. Plaintiff Merck & Co., Inc. (Merck) is a New Jersey corporation, having a place of business in Rahway, New Jersey, and is the owner, by assignment, of the ’794 and '302 patents. Defendant Chase Chemical Company (Chase), is a New Jersey corporation, having a place of business in Newark, New Jersey. Defendants Sidney and Randolph Chasman, are residents of New Jersey, and President and Secretary-Treasurer, respectively, of Chase. ...... Defendant Arroyo Pharmaceutical Corporation (Arroyo), is a Puerto Rican corporation, having a manufacturing plant in Arroyo, Puerto Rico. This Court has jurisdiction over the subject matter and of the parties to this action. This is admitted by defendants, as is also the proper laying of venue. 35 U.S.C.A. §§ 271 and 281; 28 U.S.C.A. §§ 1338(a), 1391(e), 1400(b), 2201 and 2202. The action was tried to the Court on the issues of validity and infringement of the ’794 and '302 patents as raised by Merck’s original, amended, and supplemental complaints, and defendants’ answers thereto, and on defendants’ counterclaims for a declaratory judgment of invalidity and non-infringement of the patents. Merck seeks a permanent injunction, an accounting for damages, and an award of treble damages and reasonable attorneys’ fees because of the alleged “deliberate and wilful” infringement of the patents by defendants. The ’794 patent, entitled “Vitamin B-12” issued on August 7, 1951, in the names of Edward L. Rickes and Thomas R. Wood, as co-inventors, on an application, Serial No. 108,668, filed August 4, 1949. Said application is stated in the patent to be “a continuation-in-part of our pending applications, Serial No. 20,-356, filed April 10, 1948, now abandoned, and Serial No. 38,175, filed July 10, 1948.” The invention of the ’794 patent is said to relate “to the preparation and isolation of a therapeutically valuable substance and more particularly, to the preparation of a substance obtained by the cultivation of suitable strains of the microorganism STREPTOMYCES GRISEUS in suitable culture mediums”. It is further stated that the “new chemical compound”, which Rickes and Wood named “vitamin B-12”, is “capable of promoting the growth of LACTOBACILLUS LACTIS Dorner, and possesses marked and effective action in the therapeutic treatment of Addisonian pernicious anemia and other macrocytic anemias.” The ’794 patent contains but one claim, a product claim, which reads as follows: “The compound vitamin B-12, an organic substance containing cobalt, together with carbon, nitrogen, hydrogen, oxygen, and phosphorous, said compound being a red crystalline substance soluble in water, methyl and ethyl alcohol and phenol, and insoluble in acetone, ether and chloroform, and exhibiting strong absorption maxima at about 2780 A., 3610 A. and 5500 O A., and an L.L.D. activity of about 11,-000,000 L.L.D. units per milligram.” The ’302 patent, entitled “Vitamin B-12 Active Composition and Process of Preparing Same”, issued on March 1, 1955, also in the names of Rickes and Wood, as co-inventors, on an application, Serial No. 324,834, filed December 8, 1952. Said application is stated in the patent to be “a continuation-in-part of our co-pending applications Serial No. 38,175, filed July 10, 1948, now abandoned, Serial No. 110,222, filed August 4, 1949, now Patent No. 2,695,862, and Serial No. 146,404, filed February 25, 1950, which applications are, in turn, continuations-in-part of our application Serial No. 20,356, filed April 10, 1948, now abandoned.” The invention of the ’302 patent, as set forth therein, “is concerned generally with the production of valuable vitamin products by fermentation. More particularly, it relates to vitamin B-12 active concentrates which possess animal protein factor (APF) activity, and which can be characterized by their property of promoting the growth of the microorganism LACTOBACILLUS LAC-TIS Dorner (L.L.D.), and to methods for producing such vitamin B-12 active, APF-active and L.L.D .-active materials utilizing selected strains of microorganisms belonging to the subphylum Fungi. These vitamin B-12 active concentrates are valuable as feed supplements and for the treatment of nutritional diseases.” The ’302 patent contains 12 claims, but of these only product claims 1, 2 and 3, and process claims 4, 5, 6, 11 and 12 are at issue. The product claims are practically identical and differ only in the minimal limit of the L.L.D. activity at 440, 1500 and 65,000 L.L.D. units per milligram in each claim, respectively. Product claim 1 is typical and reads as follows: “1. A vitamin B-12 active composition comprising recovered elaboration products of the fermentation of a vitamin B-12 activity producing strain of Fungi selected from the class consisting of Schizomycetes, Torula, and Eremothecium, the L.L.D. activity of said composition being at least 440 L.L.D. units per milligram and less than 11 million L.L.D. units per milligram.” Of the process claims of the ’302 patent in issue, claim 5 is typical and reads as follows: “5. A process for the production of a vitamin B-12 active composition which comprises fermenting an aqueous nutrient medium under submerged aerated conditions by means of a vitamin B-12 activity producing strain of Fungi selected from the class consisting of Schizomycetes, Torula, and Eremothecium, extracting vitamin B-12 active substances therefrom, and recovering from the resulting extract a vitamin B-12 active composition having an L.L.D. activity of at least 440 units per milligram.” Process claim 4 differs from 5 in defining the process as one for the production of an L.L.D. active composition; process claim 6 differs from 5 in specifically limiting the vitamin B-12 activity producing organism to a strain of Schizomycetes; process claim 11 differs from 5 in reciting the lower limit of L.L.D. activity of the vitamin B-12 active composition produced in accordance with the claimed process as being at least 1500 L.L.D. units per milligram; and process claim 12 differs from 5 in reciting the lower limit of L.L.D. activity as at least 1500 and in limiting the vitamin B-12 activity producing organism recited in said claim to a vitamin B-12 activity producing strain of Schizomycetes. It may be noted here that in connection with product claim 1, and process claims 4, 5 and 6 of the ’302 patent, Merck asserts that the lower limit of 440 L.L.D. units per milligram as recited in said claims, excludes such impractical and low potency fermentation products as may have existed in nature, and that a composition having a vitamin B-12 activity of at least 440 L.L.D. units per milligram, within the language of the claims, is sufficiently potent and concentrated to insure freedom from undesirable or toxic materials. For a better understanding of the issues involved in this litigation, some recital of the history leading to the issuance of the patents in suit is necessary. Prior to 1926, medical science could offer very little help to persons afflicted with the disease of pernicious anemia. But in 1926, Doctors Minot and Murphy, of Harvard Medical School, found that pernicious anemia patients were benefited by the addition to their diets of substantial quantities of the liver of cattle. For this discovery Minot and Murphy received the Nobel Prize. But neither they nor anyone else knew what it was in liver that controlled the disease. The Minot-Murphy discovery spurred efforts by medical and pharmaceutical workers throughout the world to attempt to isolate and identify the factor in liver that was responsible for the beneficial anti-pernicious anemia effect. The search for the anti-pernicious anemia factor (APAF) in liver was long and tedious. New extracts and concentrates of liver were developed, but they could only be tested by administration to pernicious anemia patients in relapse, and opportunities for such clinical testing were not plentiful. By 1947, however, a number of liver extracts and concentrates were on the market. These preparations reduced substantially the dosage amounts required by patients, but some patients were unable to tolerate them, and they were expensive. Just what it was in liver that was responsible for the anti-pernicious anemia factor remained a matter of speculation. Some researchers were of the opinion that multiple factors were involved. Others thought the factor was a hormone produced within the body of the animal. Still others believed it might be a vitamin formed in the liver of cattle after slaughter by postmortem autolysis. Tests, however, indicated no relationship between the liver fractions and the then known vitamins. In short, it may be said that there were as many different theories concerning the identity of ■ the beneficial substance in liver as there were investigators. An indication of the scope and complexity of the problem that confronted the investigators in their efforts to isolate and identify the anti-pemicious factor in liver is disclosed in a joint report published in 1945 by Dr. Subbarow, Research Director of Lederle Laboratories, Dr. Elkin, also of Lederle, and Dr. Hastings of Harvard Medical School. The purpose of this report was to make known “[t]he progress made since 1926 toward the isolation and identification of the anti-pernicious anemia material of liver.” These researchers, after an analysis of all the then current learning on the subject, and a consideration by them of the 129 articles cited in their report, could only conclude that: “It is, unfortunately, apparently not possible at the present time [1945] to reconcile the various claims and facts regarding the material or materials which are present or capable of extraction from liver, and which are therapeutically active in pernicious anemia.” Efforts to isolate and identify the APAF in liver continued. On June 10, 1946, Dr. Thomas R. Wood, one of the patentees named in the ’794 and ’302 patents, entered the employ of Merck. One of his first assignments was to attempt to isolate the anti-pernicious anemia factor or factors in liver. Earlier attempts by Merck to do this had proved unsuccessful and were abandoned. Dr. Wood worked on various fractionations of liver concentrates, using clinical testing to check the potency of the fractions. However, as previously stated, this type of testing was a slow process, depending as it did on the availability of suitable patients and the time necessarily required to ascertain the results obtained by the liver concentrates in individual cases. The lack of a good assay or test hampered the efforts of investigators to achieve the desired objective. An assay procedure that would expedite the work was needed. Such an assay was developed by Dr. Mary Shorb. Dr. Shorb was a bacteriologist employed by the United States Department of Agriculture, and later connected with the Department of Poultry Husbandry at the University of Maryland. In 1946, she was conducting experiments designed to develop an assay or test for an unidentified rat growth factor found in liver extracts and other foodstuffs. For this purpose, Dr. Shorb selected the microorganism Lactobacillus lactis Dorner. Using liver products having a determined value in the treatment of pernicious anemia, she noted that the rate of growth of the organism Lactobacillus lactis Dorner (L.L.D. activity), varied in an almost linear relation to the indicated anti-pernicious anemia potencies of the liver extracts she tested. This led Dr. Shorb to speculate that her assay might be useful in liver fractionation work, but of this she could not be certain because it was found that the organism she was testing was also responsive to materials, other than liver, which did not contain any anti-pernicious anemia activity. In November 1946, Dr. Shorb’s work came to Merck’s attention. A limited number of liver samples were thereupon sent by Merck to Dr. Shorb at the University of Maryland for assay and a report on the L.L.D. activity of the samples submitted. Thereafter, on February 1, 1947, Merck entered into a contract with the University of Maryland, pursuant to which Dr. Shorb was to continue her efforts to perfect an assay for the anti-pernicious anemia factor. In furtherance of this program, it was agreed that Dr. Shorb would test, with her assay procedure, for L.L.D. activity, such materials as might be forwarded to her by Merck. For convenience in testing, use was made of an existing liver extract to which was arbitrarily assigned a potency of 1000 L.L.D. units per milligram. This became the standard against which L.L.D. active products were to be measured. The state of development of Dr. Shorb’s assay as of May 1947, is indicated by her statement that “[b]ecause of many variables influencing the growth of L. lactis Dorner, further work is needed in the separation of the various factors before accurate assay methods can be worked out. L. lactis Dorner should be of value in the further study of these factors and their relation to anemias.” Notwithstanding the need for work “before accurate assay methods can be worked out”, Merck admits that the L.L.D. assay, as developed by Dr. Shorb, was a tool of major assistance in the search for the anti-pernicious anemia factor. It was used by Dr. Wood to check the potency of the various liver fractions he was testing, with a considerable saving of time over the slower clinical testings that were dependent upon the availability of pernicious anemia patients. But the record does not support any finding that the Shorb assay pointed to fermentation materials as a source of the anti-pernicious anemia factor. In addition to the work on liver, Merck also undertook the study of fermentation materials as a possible source of the anti-pernicious anemia factor or factors. In June 1947, Edward L. Rickes, the co-inventor named with Dr. Wood in the ’794 and ’302 patents, was assigned by Wood to make this study. From that time forward, the research work at Merck proceeded along two lines: (1) the investigation of fermentation materials as a possible source of the anti-pernicious factor, and (2) the isolation and identification of that factor in liver. Wood worked with and supervised the Rickes fermentation investigation while he, Wood, continued his work on liver fractionations. Rickes experimented with, and performed, extraction operations on a number of materials derived from fermentation sources, samples of which would be sent to Merck’s Microbiology Department for L.L.D. assay. Among the samples was an extract of grisein broth. Grisein was an antibiotic then being made and under study by Merck, but it was never successfully developed as an antibiotic for commercial use. This grisein was produced by a particular strain of Streptomyces griseus, a microorganism that is grown in a nutritional broth under aerobic conditions. Of all the fermentation products tested, grisein was selected as the most suitable for further experimentation. By September 16, 1947, Rickes and Wood succeeded in recovering from grisein fermentation source materials, compositions having a potency of over 440 L.L.D. units per milligram, the range being from 514 to 1200. These compositions of at least 440 L.L.D. units per milligram are said to come within the terms of claim 1 of the ’302 patent. Upon obtaining these results, research was intensified, and included extractions, concentrations, and chromotographic fractionations of grisein materials, in an effort to isolate therefrom the anti-pernicious anemia factor. On October 22, 1947, Rickes noted a pink or reddish color in some of the fractions, the recurrence of which was found to. be correlated with the activity of the materials. Samples of grisein concentrates, tested by Merck’s nutritional expert, Dr. Ott, who found them to be successful in promoting the growth of chicks. On December 11-12, 1947, Rickes, for the first time, obtained red crystals from a water solution of a grisein fermentation extract upon the addition of acetone thereto. These red crystals, upon assay, yielded an average reading of 11,000,000 L.L.D. units per milligram. This, says Merck, was the first isolation of the anti-pernicious factor, and is the compound described and claimed in the ’794 patent. The acetone-water crystallization technique used by Rickes to obtain red crystals from fermentation materials was subsequently found to be successful in extracting the anti-pernicious anemia factor in crystalline form from liver. In March 1948, the red crystalline material obtained from liver and from fermentation were compared and found to be identical. The crystals from both sources were successfully chick tested, and were also successfully tested clinically on patients suffering with pernicious anemia. Thereafter, on April 10, 1948, the first Rickes and Wood application on vitamin B-12, Serial No. 20,356, was filed. Consideration will now be given to the issues raised by the pleadings in this case. Passing for the present the presumption of validity that attaches to patents by virtue of section 282 of the Patent Act of 1952, 35 U.S.C.A. § 282, section 101 of the Act, 35 U.S.C.A. § 101, authorizes the issuance of a patent for “any new and useful * * * composition of matter”, provided, of course, that there is a compliance with the other statutory conditions of patentability. Merck claims that the vitamin B-12 compound of the ’794 patent, and the vitamin B-12 active compositions of the ’302 patent, are new and useful compositions of matter; that the same can be produced in adequate quantities by fermentation processes under man-controlled conditions, and sold commercially for medicinal and nutritional purposes; that such products were not available prior to their invention by Rickes and Wood; that the products supplied a long-felt need in eliminating the disadvantages of liver extracts in the treatment of pernicious anemia, and also, in the field of animal husbandry, for a dietary growth supplement; and that these products have met with commercial success and acceptance. Defendants disagree, and they first attack the validity of the ’794 and ’302 patents on the ground that the patent specifications fail to meet the requirements of 35 U.S.C.A. § 112. That section lays down the rule that a patent specification must disclose the invention in such clear 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 * * *» One contention made under this section 112 defense is that the patents lack a sufficient description of the strains of organisms used to produce vitamin B-12 or vitamin B-12 active materials in terms of an identifying number for a culture deposited in a culture collection. Defendants argue that this information could have been included in the patent specifications, and that the failure to do so renders the specifications insufficient under the statute. This argument is premised on the assumption that a person skilled in the art would be required “to conduct [his] own screening and fermentation program, including isolation of strains from various sites, and cultivation of the strains under conditions to be developed by the investigator for the particular strain before [he] can attain an organism capable of producing B-12 active material.” The evidence does not sustain the position taken by defendants on this phase of the case. It is, of course, well settled, that a patent is invalid for insufficient ' disclosure if, in order to practice the invention, a person skilled in the art must resort to elaborate experimentation, independent investigation, or exercise inventive skill. Standard Brands v. National Grain Yeast Corp., 101 F.2d 814 (3 Cir. 1939); Standard Oil Co. of California v. Tide Water Associated Oil Co., 154 F.2d 579 (3 Cir. 1946). But such is not the situation here. The fact that preliminary tests may have to be made will not invalidate a patent for insufficient disclosure when the character and limitations of the tests are well known to the art. The particularity and certainty of disclosure that the law requires in patents is not greater than is reasonable, having regard to their subject matter. Minerals Separation, Ltd. v. Hyde, 242 U.S. 261, 37 S.Ct. 82, 61 L.Ed. 286 (1916); Locklin v. Switzer Bros. Inc., 299 F.2d 160 (9 Cir. 1961). Defendants are attempting to equate the specifications of the '794 and ’302 patents with the specification that was found to be insufficient in Ex parte Kropp, 143 USPQ 148 (POBA 1959). That case is clearly distinguishable on its facts. The organism used as the starting material in Kropp, which had been isolated from a soil sample obtained in Pennsylvania, could not be reproduced from the written description, nor did the specification give any source where it could be found. Reproduction of the invention (an antibiotic) from the Kropp specification, in the words of the appellate Examiner in Chief, “* * * would require the initiation of a screening program similar to the screening programs followed in discovering antibiotics in the first instance. Such a program would involve the collection of soil samples from different sources, making cultures from the samples, isolating organisms, reculturing the isolates, and testing the resultant cultures to determine if the particular antibiotic was produced. If the organism involved in the production of the antibiotic were of very common occurrence it might be found in a relatively short time, but if it were not of common occurrence it might not be found for a very long time, if found at all, and if it were a chance variation, the time before it was rediscovered might be extraordinary, or it might even never be found.” It thus becomes apparent why the specification in Kropp was held insufficient. It was pointed out, however, that if Kropp involved “ * * * a known organism which had a well defined source and which had been obtained and used by others before, or even with an organism which was merely known and available to persons skilled in the art * * * ”, the question of the sufficiency of the disclosure would not have arisen. The specifications in the case at bar deal with known and available organisms. The patents pertain to the arts of chemistry and microbiology, and their specifications are addressed to persons skilled in those sciences. The ’794 patent makes specific reference to a grisein producing strain of Streptomyces griseus suitable for the production of vitamin B-12. There was uncontradicted testimony that as of April 10, 1948, the date on which the first Rickes and Wood application (Serial No. 20,356) on vitamin B-12 was filed, there was available at Rutgers University, in a stock culture collection, a grisein producing strain of Streptomyces griseus; that this organism was suitable for the production of vitamin B-12; that it could be obtained by anyone for experimental or commercial use; and that the identification of that particular strain had been made and published by Rutgers in January 1947. There was also undisputed testimony that the grisein producing strain of Streptomyces griseus was the only strain of that microorganism mentioned in the Rutgers publication; that it was this strain that Merck requested and got from Rutgers; that this same strain has been and still is available, and that anyone requesting it would get what Merck got, namely, a strain of Streptomyces griseus suitable for the production of vitamin B-12. The ’794 specification teaches how the claimed compound of the patent may be obtained by the cultivation of suitable strains of the microorganism Streptomyces griseus in a suitable culture medium. The specification describes, as á starting material, a crude L.L.D. active concentrate of Streptomyces griseus elaboration products, and tells how that concentrate, which produces L.L.D. active ingredients from which vitamin B-12 may be derived, can be prepared. A person skilled in the art would need only to conduct a fermentation of the organism selected and assay the elaboration products for L.L.D. activity. The testimony was uncontradicted that a trained chemist, by following the teachings of the ’794 patent, would be able to produce vitamin B-12, and that the fermentation processes and L.L.D. assays described in said patent are procedures that are well understood and easily performed by those skilled in the art. In the ’302 specification, reference is made to a number of different organisms within the classes Schizomycetes, Torula and Eremothecium which are useful in the production of vitamin B-12 active compositions. The specification gives 13 examples of the use made of a number of these organisms to produce the claimed compositions, suitable nutrients, and different recovery techniques for obtaining vitamin B-12 active compositions. A number of tests are also set forth by means of which the proper strain of organism capable of producing vitamin B-12 active compositions may be selected. Here again, the testimony establishes that a trained microbiologist, by following the teachings of the ’302 patent, would be able to produce vitamin B-12 active compositions. Por the reasons stated, the Court is satisfied that the omission to describe the organisms mentioned in the ’794 and ’302 specifications in terms of identifying numbers in a publicly available culture collection, does not render the specifications insufficient under 35 U.S.C.A. § 112. There is no factual basis to support defendants’ contention that this lack of disclosure would require a person skilled in the art to conduct an extensive screening and fermentation development program, tantamount to discovery, before he could attain an organism capable of producing vitamin B-12 materials. The evidence is to the contrary. Another attack for insufficiency of disclosure under 35 U.S.C.A. § 112, directed to the ’794 patent, is that the crystalline fraction, which is the end-product obtained by the '794 recovery procedure, is not pure vitamin B-12, later called cyanocobalamin, but is a complex crystal, in which cyanocobalamin is mixed with other cobalamins. In this connection it is pointed out that the “cobalamin” nomenclature did not exist at the time the ’794 patent was issued. This nomenclature, say defendants, came later, after the molecular structure of the vitamin was elucidated and found to be plural in nature. As a family, the molecules were called “cobalamins”, and the most stable of them, the one having a “cyano” group in the molecule was named “cyanocobalamin”. It is contended that it was not until late 1949, after the plural nature of the vitamin was known and the cyano form differentiated, that the distinction between “B-12” and “B-12-like” was made by Merck, at which time the name “vitamin B-12” was confined to the cyano form, and the other cobalamins were called “B-12-like” compounds. Defendants argue that before the plural nature of the material was uncovered, vitamin B-12 meant simply the product obtained by the recovery procedure described in the ’794 patent, a mixture of cobalamins, and not the “pure, crystalline cyanocobalamin vitamin B-12”, claimed as the patented product. In support of the foregoing, defendants refer, inter alia, to the ’302 patent and three other patents owned by Merck: WOLF (2,530,416), issued November 21, 1950; DENKEWALTER (2,678,900), issued May 18, 1954; and KACZKA (2,738,301), issued March 13, 1956. This argument, which laboriously threads its way through the massive record in this case, is without substance. It takes, as an admitted fact, that a, Streptomyces griseus fermentation, such as the ’794 patent uses for its starting material, produces in its broth, a mixture of cobalamins. Hence it is argued “as a minimum first proposition”, that “there can be no doubt of the possibility that a crystalline fraction recovered from the broth of such fermentation is likewise a mixture of cobalamins.” Assuming this to be true, it does not at all follow that such a mixture, when subjected to the ’794 recovery procedure, does not yield the claimed compound of that patent. Examples 7 and 8 of the ’302 patent are cited by defendants to show that the crystalline precipitate from a Streptomyces griseus broth is a complex crystal, containing both vitamin B-12 and vitamin B-12-like substances. But the fact is, although defendants attempt to minimize it, that the recovery procedure used in the cited examples, differed from the recovery procedure described in the ’794 patent. The Wolf patent relates to procedures for converting vitamin B-12-like substances to vitamin B-12. The patent is cited as being the first disclosure of the existence of several active forms of vitamin B-12 producing compounds, and of the use of cyanamid ions to effect conversion of the vitamin B-12-like substances to pure vitamin B-12. This later-in-time “first disclosure” in no way establishes that the recovery procedure of the ’794 patent was incapable of producing pure vitamin B-12. The evidence hereinafter mentioned shows otherwise. The Denkewalter patent covers new and improved procedures for the recovery of vitamin B-12. It describes a fractionation system that may be used either to improve the recovery of the several B-12 active substances as one mixed product, free of inactive impurities, or to selectively recover vitamin B-12 free of the other active substances. The patent is cited to show that concentrates from Streptomyces griseus fermentations are mixtures of B-12 active substances, and also to highlight the difficulties experienced with the ’794 style of recovery in the separation of B-12 active substances and associated impurities. Defendants assert that nothing like the Denkewalter fractionation system is described in the ’794 patent, and that it is evident that without some such effective further fractionation, the ’794 patent yields only a crystalline mixture and not pure cyanocobalamin. Again, the evidence is to the contrary. There is no question that the Denkewalter patent teaches a more efficient recovery method to obtain pure cyanocobalamin. But this later acquired knowledge can have no bearing on the validity of the ’794 patent. The sufficiency of the disclosure of the ’794 patent must be measured in terms of the specification as of the time it was written and passed upon by the Patent Office. The Kaczka patent relates to the preparation of a chemically modified form of vitamin B-12, called vitamin B-12a or hydroxocobalamin. This patent is said by defendants to provide the most pertinent evidence in the record concerning the true nature of the product resulting from the ’794 recovery procedure, in that said patent shows that a red crystalline precipitate obtained thereby, from a Streptomyces griseus broth, is a mixture of cobalamins in which the cyanocobalamin content can be only about one-half. Attention is also called to the fact that the Kaczka patent discloses a close similarity of the “absorption maxima” curves of B-12 and B-12a, and the need for a special procedure, because of the wide difference in their partition coefficients, to separate the cyano form of cobalamin from the hydroxo form, when both are in a crystalline mixture. Defendants argue that the intelligence imparted by the Kaczka patent is proof that the ’794 recovery procedure will not produce pure cyanocobalamin. But again, the proof is to the contrary. In sum then, defendants argue that viewed in light of the disclosures of these later dated Merck patents, and other evidence in the case, it is clear that the ’794 patent does not teach a fractionation procedure by which to recover pure cyanocobalamin, free of other B-12 active compounds ; that such procedure, at best produces a mixture of cobalamins, with whatever inactive materials come with it; and that in order to obtain pure cyanocobalamin, resort must be had to purification steps not taught in the ’794 specification. The evidence is practically uncontradicted that by following the teachings of either the first Riekes and Wood application, Serial No. 20,356, filed April 10, 1948, or the ’794 patent, a person skilled in the art, a trained chemist, would produce pure crystalline vitamin B-12, the claimed compound, now known as cyanocobalamin. In the ’794 patent, a number of distinguishing characteristics of vitamin B-12 are set forth, including the wavelengths and absorption intensities of the compound and its partition coefficient in toluene, ortho-cresol and water, and water/benzl alcohol systems. The patent teaches that when a crystalline product or a high degree of purification is wanted, “[t]he crystals may be redissolved in water and precipitated with acetone several times to remove any impurities that may still remain.” Developments at different stages of the recovery procedure are noted so that the trained chemist would know whether or not the operation is progressing satisfactorily, and would also be able to determine that the end-product obtained was pure cyanocobalamin and not hydroxo or other forms of cobalamin. Dr. Earl Pierson, a chemist employed by Merck, and the holder of degrees in organic chemistry, testified that the '794 patent disclosed pure crystalline vitamin B-12, now known as cyanocobalamin, and that the ’356 application filed April 10, 1948, likewise made a similar disclosure. Dr. Pierson further testified that a skilled chemist, following example 2 of said application, would obtain cyanocobalamin of 90-95% purity; also, that there was teaching in the ’356 application that would enable the skilled chemist to improve the purity of the cyanocobalamin so obtained, if necessary; and that the purity of cyanocobalamin obtained by one crystallization could be improved by re-crystallization, a technique that was well known and in common use in 1947. Edward L. Rickes, one of the co-inventors named in the ’794 patent, testified that in January 1948, he produced a batch of crystals, designated as sample 481-30A, in accordance with example 2 of the patent, which is practically identical with the same numbered example in the ’356 application. He did not use any “countercurrent distribution” procedure on the crystals. This same sample, 481-30A, was tested in February 1948, by Merck’s research chemist, Dr. Donald E. Wolf. He ran a countercurrent distribution on the crystals and found them to be 98-99% pure cyanocobalamin. The sufficiency of the disclosures of the ’794 and ’302 patents passed muster in the United States Patent Office. While this, of course, is not binding on this Court, it is a factor to be considered in light of the expertise and competence that the trained personnel of the Patent Office bring to bear on problems involved in matters of this kind. Moreover, and more importantly, th'e Court is satisfied, upon a consideration of the evidence in this case, that the ’794 and ’302 patents fully satisfy the requirements of 35 U.S.C.A. § 112. See Guaranty Trust Co. of New York v. Union Solvents Corp., 54 F.2d 400 (D.Del.1931), aff’d 61 F.2d 1041 (3 Cir. 1932). What has already been said also disposes of the argument directed to the alleged insufficiency of the 1948 applications mentioned in the ’794 and ’302 patents. These are the so-called “parent” applications, Serial No. 20,356 filed April 10, 1948 and Serial No. 38,175 filed July 10, 1948. Defendants contend that the failure to set forth in said applications a sufficient description of the organisms suitable for the production of vitamin B-12 and vitamin B-12 active compositions, and the failure to sufficiently describe the claimed subject matter of the patents, render the applications fatally defective, under 35 U.S.C.A. § 120, as a proper basis upon which said patents may rely for their effective filing dates. The lack of sufficient descriptions of the organisms centers around the omission to describe or refer to any publicly available culture collections in which strains of the organisms mentioned in the applications may be found or from which they may be obtained. But as mentioned earlier in this opinion, the organisms named in the applications and in the patents are well known organisms to persons skilled in the art, and available. Defendants have not shown the fact to be otherwise. As to lack of sufficient description in the applications of the claimed subject matter of the patents, the argument here is a repetition of that advanced in connection with the alleged insufficiency of disclosure of the patent specifications. For reasons already stated, there is no merit to this contention. The evidence clearly establishes that a person skilled in the art, whether reference is had to the applications or the patents, will be able, by following the teachings therein set forth, to produce the claimed compound of the ’794 patent and the claimed compositions of the ’302 patent. It follows, and the Court so finds, that the applications for the ’794 and ’302 patents were valid continuations-in-part of the ’356 and ’175 applications, and that the patents are entitled to their filing dates of April 10 and July 10,1948. See General Talking Pictures Corp. v. Western Electric Co., 304 U.S. 175, 183, 58 S.Ct. 849, 82 L.Ed. 1273 (1938); Clark Blade & Razor Co. v. Gillette Safety Razor Co., 194 F. 421, 422 (3 Cir. 1912). The validity of the ’794 patent is also attacked on the ground that it creates an excessive and unlawful monopoly. It is contended that the patentees did not invent the claimed compound, vitamin B-12, but merely recovered it, from an existing material containing it, in a more nearly pure condition than it had been in before. Defendants further contend that the patented product represents, not a newly created compound, but only a purified form of the anti-pernicious anemia factor (APAF) that had existed and was known to be present in liver, and that such being the case, the product monopoly asserted by Merck under the ’794 patent, cannot legally be sustained. In other words, the compound claimed in the patent is not “new” since it existed before in the parent material, and it is not “inventive”, as a product, because the concept of it was obvious. 35 U.S. C.A. §§ 101 and 103. In support of these contentions, defendants point to the work on liver done by a number of investigators, including La-land and Klem in Norway; Strandell in Sweden; Emery, Parker, Hurran and Smith in England; and Murphy in this country. Reference is also made to the commercial liver extracts of Lederle Laboratories, Inc. and Eli Lilly and Company. The work of Laland and Klem (1936), and Laland (1939), were cited to show that these scientists had effected a 200,-000-fold concentration of the anti-pernicious anemia factor in liver, and that their product had some of the characteristics of vitamin B-12. But there is no indication that these men knew what it was in liver that controlled pernicious anemia, or that they had any understanding as to the chemical nature of whatever that something might be. The most refined liver fractions obtained by Laland and Klem were bright reddish-yellow or light orange-red in color, as contrasted with the red crystals of vitamin B-12. There was also a difference in chemical composition. An analysis of the Laland-Klem liver fractions showed the presence of carbon, nitrogen, hydrogen, and sulphur. Vitamin B-12 contains all of these elements except sulphur, plus phosphorus, cobalt and oxygen. The absorption maxima of the Laland-Klem fractions also differed from those of vitamin B-12, thus creating doubt as to whether the absorption observed in connection with the Laland-Klem material was due to the active [anti-pernicious] principle in the liver or to a contamination. And finally, Laland and Klem never obtained their substances in crystalline form. Strandell’s paper (1935), merely reported on a number of cases treated by the author with a new liver preparation called Pernami. Mention is made by Dr. Strandell that he had collaborated with Laland and Klem in experiments looking toward the isolation of “the anti-anemic principle of the liver”, and he expressed the hope that this isolation would be accomplished in the near future. The work of Emery, Parker and Hurran appears to have been primarily concerned with the problem of standardization of liver extracts and not with the isolation or identification of the anti-pernicious anemia factor or factors in liver. The Emery and Parker report (1946), which makes reference to an earlier paper (1945) by Emery and Hurran, was cited to show that a further purification of the anti-pernicious anemia factor in liver had been achieved. This further purification yielded a fraction of 1.2 milligrams from 1 kilogram of liver, and was said to have proved active in human pernicious anemia on a single dose of 1 milligram. As to this fraction, however, the report stated that it had been dried from the frozen state and was shown not to have any specific ultraviolet absorption characteristics. Regarding the liver work done by Smith, suffice it to say that it was not until April 24, 1948, which was eight days after Merck’s publication of its isolation of the anti-pernicious anemia factor from liver, that Smith wrote an article stating that he had prepared, from ox liver, two red pigments, both highly active in pernicious anemia. Defendants call attention to the fact that the Smith product, although not crystalline, was nevertheless “credited” by Merck as being an “isolation” of the anti-pernicious anemia factor. This statement is based on a note appearing in one of defendants’ exhibits. That note hardly supports the conclusion that Merck “credited” Smith’s purification of the liver fractions as an “isolation” of the anti-pernicious anemia factor. In any event, nothing like the Merck crystals eventuated from the Smith experiment. Dr. Murphy’s article, “Anemia in Practice”, published in 1939, contains an interesting history of the development of liver therapy in the treatment of pernicious anemia. The article describes the difficulties encountered in attempting to serve a sufficient quantity of liver in such a way as to be most effective and palatable for a patient who had an inherent dislike for it. Dr. Murphy then traces the development of liver extracts for peroral use for those patients who found it difficult to ingest whole liver. He then tells of the emergence of the highly concentrated and potent liver extracts that were suitable for parenteral administration. There can be no question but that following the Murphy-Minot discovery of whole liver therapy in 1926, much progress was made in the refinement, purification, and preparation, for commercial use, of liver extracts, which reduced substantially the dosage requirements for patients afflicted with pernicious anemia. These commercial liver extracts were available in 1947, and for some years prior thereto. However, as pointed out by Dr. Murphy in his 1939 article, the liver extracts that were prepared for parenteral administration, both in this country and abroad, varied greatly in concentration and potency, thus making it difficult to describe the dose and method of use of the available preparations. Dr. Murphy’s experience was largely limited to the Lederle extracts, which were found by him to be of a high standard of potency. But it is to be noted that there were pernicious anemia patients who, when treated with the commercial liver extracts, experienced unfavorable reactions, ranging from mild to severe, including “weakness, increased pulse rate and perspiration, drop in systolic pressure, pruritis, or urticaria.” Shock, and even death, sometimes occurred. In evidence in this case is a study made by Dr. Noren of Sweden in 1948, on the allergic reactions in parenteral liver therapy and vitamin B-12. Involved were 130 pernicious anemia patients, later reduced to 124, who were receiving parenteral liver treatments. Out of the reduced number, 18 were found to exhibit allergic reactions to liver. It was noted that in some cases the symptoms were quite severe, while in others the allergic reaction so increased in intensity, that parenteral liver therapy had to be abandoned. Dr. Noren then tested 9 of the more serious cases with crystallized vitamin B-12, and found a complete absence of adverse reactions, thus demonstrating that those pernicious anemia patients who could not tolerate the liver therapy, could now be helped by vitamin B-12. Defendants agree that Merck’s crystalline product, vitamin B-12, as claimed in the '794 patent, is more nearly pure, “by a substantial margin”, than the most potent earlier concentrates of the anti-pernicious anemia factor in liver. Other advantages of the patented product over the earlier liver extracts are also admitted. But, say defendants, repeating the arguments already made, these advantages do not give rise to patentability because, in the best view of the matter, the patented product is not a newly created compound, but only a purified form of the anti-pernicious anemia factor in liver, the existence and efficacy of which, to cure anemias, has been known since 1926. Defendants have cited a number of cases which enunciate the generally recognized principles that a patent may not be awarded for a product of nature, or for a substance that is merely extracted from its parent material and purified, or for a new form of an old product. Illustrative are Ex parte Sparhawk, 64 USPQ 339; Ex parte Snell, 86 USPQ 496; Ex parte Cavallito, 89 USPQ 449; Ex parte Reed and Gunsalus, 135 USPQ 34; Ex parte Hartop, 139 USPQ 525; In re King, 107 F.2d 618, 27 CCPA 754; Application of Fisher, 307 F.2d 948, 50 CCPA 1025; General Electric Co. v. De Forest Radio Co., 28 F.2d 641 (3 Cir. 1928). De Forest is a good example of a typical “product of nature” case. It involved the Coolidge patent for “tungsten and a method of making the same for use as filaments of incandescent electric lamps and for other purposes.” It appears that tungsten in its natural state as found in the earth is brittle. What Coolidge did was to invent a process to purify the natural product. Tungsten in this state, he discovered, had the characteristics of ductility and high tensile strength. The broadest product claim in the Coolidge patent was for “ [substantially pure tungsten having ductility and high tensile strength.” As against the patentee’s assertion that he created “substantially pure tungsten”, the court held he did not because the product existed in nature. As to the additional words of the claim, “having ductility and high tensile strength”, the court said this was merely descriptive of the subject matter. In brief, the court found that Coolidge neither created pure tungsten, nor its characteristics. Both qualities, said the court, were created by nature. The validity of the patent was thus limited to the method Coolidge disclosed for converting the natural product into purer form. It is interesting to note, as did the court in De Forest, that Coolidge did not seek a patent for “a new composition of matter”, but instead claimed as the subject matter of his patent, a product which, upon reference to the patent specification, was found to be the “tungsten of nature”. It is also interesting to note that the state of the art, long before Coolidge, disclosed the use of tungsten as a filament for an incandescent lamp, and also how to make a wire of tungsten. There can be no quarrel with the holdings in De Forest and other cases cited by defendants, but they are not controlling here. Each case must be decided upon its own facts. Incidentally, no assertion is made on this branch of the case that Merck’s patented composition was anticipated under 35 U.S.C.A. § 102. The date of the invention here is December 11-12, 1947, and it is clear that no single prior art patent or publication disclosed the vitamin B-12 compound claimed by the ’794 patent. See Dewey & Almy Chemical Co. v. Mimex Co., 124 F.2d 986, 989 (2 Cir. 1942). Patentability rests, then, upon a determination of whether the ’794 patent covers a “new and useful * * * composition of matter”, and, if so, whether the disclosures of the prior art, notwithstanding lack of anticipation, nonetheless negative patentability because of obviousness. The record in this case fully supports patentability when viewed in light of utility, novelty and non-obviousness of the subject matter. See in this connection the following cases: Kuehmsted v. Farbenfabriken of Elberfeld Co., 179 F. 701 (7 Cir. 1910); Union Carbide Co. v. American Carbide Co., 181 F. 104 (2 Cir. 1910); Parke-Davis & Co. v. H. K. Mulford Co., 189 F. 95 and 196 F. 496 (2 Cir. 1912); Smith, Kline & French Laboratories v. Clark & Clark, D.C., 62 F.Supp. 971, aff’d 157 F.2d 725 (3 Cir. 1946); Union Carbide & Carbon Corp. v. Stuart Laboratories, 194 F.2d 823 (3 Cir. 1952); Bristol Laboratories v. Schenley Laboratories, 117 F.Supp. 67 (S.D.Ind.1953); Charles Pfizer & Co. v. Barry-Martin Pharmaceuticals, 241 F.Supp. 191 (S.D.Fla.1965). It cannot be seriously disputed, on this record, that the claimed compound of the ’794 patent constitutes a new and useful composition of matter. It certainly was not disclosed or even suggested in or by the prior art. The prior art was liver-oriented. All efforts to isolate and identify the anti-pernicious anemia factor were directed to liver sources. The factor continued to remain unidentified and unknown. The ’794 patent, of course, does not deal with liver. The claimed subject matter, pure cyanocobalamin or vitamin B-12, is a red crystalline substance derived from a fermentation source. The record amply supports the conclusion that the idea to investigate fermentation materials as a possible source of the anti-pernicious anemia factor originated with the patentees, Rickes and Wood, and that it was not suggested to them by anyone else. Before Rickes and Wood made it available to the world, pure crystalline vitamin B-12, as described and claimed in the ’794 patent, did not exist. No one had produced even a comparable product. The new product had such advantages over the earlier liver extracts that it not only replaced them, but became, and remains to this day, the universal treatment for pernicious anemia. The new product has completely eliminated the harmful side effects of the old liver preparations. Moreover, crystallization of the claimed compound was significant in that it established for the first time that the anti-pernicious anemia factor could be obtained in crystal form, susceptible to any desired degree of purification, and also to physical and structural determination. It also made possible standardization, by weight, of the exact dosage required by patients. Further evidence of the utility of the ’794 invention from a medical standpoint may be found in defendants’ own advertising brochure enclosed with each of their vitamin B-12 products, wherein it is stated, inter alia, that: “Vitamin B-12 is probably the most potent hematopoietic substance known. Since it is identical with the anti-anemia factor in liver, it is fully as effective as liver injection USP. It provides prompt and favorable response in the treatment of primary pernicious anemia. * * * No known toxic effects for oral or parenteral administered Vitamin B-12 have been reported. No chronic or cumulative toxic effects have been observed even with massive doses. There are no known contraindications. Although a very few reactions have been noted, evidence indicates that it is particularly useful in the treatment of patients sensitive to pork or beef liver extracts.” In a similar vein, it was brought out on cross-examination of defendants’ witness, Harry J. Konen, that in a talk given by him at a nutritional conference, he stated that he regarded the isolation by Merck of the anti-pernicious anemia principle, and the research work relative thereto, as one of the most important developments in the field of nutrition from the standpoint of both basic science and scope of application, whether commercially in the feed industry or in human nutrition. The state of the prior art, as reflected by this record, does not support defendants’ argument that the subject matter of the ’794 patent was obvious. The proofs point in the direction of non-obviousness. No one, before Rickes and Wood, succeeded in isolating and identifying the anti-pernicious anemia factor that had theretofore been associated only with liver. The chemical nature of that factor was unknown and was the subject of many theories and speculations. No one, other than Rickes and Wood, conceived the idea that fermentation materials might be a source of the anti-pernicious anemia factor. This Court is satisfied that the patentees of the ’794 patent have given to the world, for the first time, a medicine that can be used successfully in treating all patients suffering with pernicious anemia, a medicine that is subject to accurate standardization, and avoids the unfavorable reactions of the earlier liver extracts. It did not exist in nature in the form in which the patentees produced it, and nothing in the prior art either suggested or anticipated it. In considering the question of obviousness under 35 U.S.C.A. § 103, the prior art must be viewed from the point in time just prior to when the invention was made. Many things may seem obvious after they have been made, hence courts must guard against the use of hindsight. See Diamond Rubber Co. of New York v. Consolidated Tire Co., 220 U.S. 428, 435, 31 S.Ct. 444, 55 L.Ed. 527 (1911); Craft-Stone, Inc. v. Zenitherm Co., 22 F.2d 401, 402 (3 Cir. 1927); Marvel Specialty Company v. Bell Hosiery Mills, Inc., 330 F.2d 164, 172 (4 Cir. 1964); Monroe Auto Equipment Co. v. Heckethorn Mnfg. & Sup. Co., 332 F.2d 406, 412 (6 Cir. 1964). The difficulty of determining subjectively at some removed time whether a particular invention would have been obvious to a person of ordinary skill in the art, invites a consideration of objective criteria of obviousness. See Reiner v. I. Leon Co., 285 F.2d 501 (2 Cir. 1960). As was stated by Mr. Justice Clark in Graham v. John Deere Co., 383 U.S. 1, 17, 86 S.Ct. 684, 694, 15 L.Ed.2d 545 (1965): “Under § 103, the scope and content of the prior art are to be determined; differences between the prior art and the claims at issue are to be ascertained ; and the level of ordinary skill in the pertinent art resolved. Against this background, the obviousness or nonobviousness of the subject matter is determined. Such secondary considerations as commercial success, long felt but unsolved needs, failure of others, etc., might be utilized to give light to the circumstances surrounding the origin of the subject matter sought to be patented. As indicia of obviousness or nonobviousness, these inquiries may have relevancy.” In the case at bar, the ’794 patented product met with great commercial success and acceptance. While these factors alone do not give rise to patent-ability, if none in fact exists, yet it is permissible to take them into consideration on the issue of obviousness or nonobviousness. A Merck witness testified that the first sale of crystalline vitamin B-12 by Merck was made in 1949, and consisted of 7 grams of that product, each gram of which was sold for $12,500.00. All 7 grams were purchased by Merck competitors, including 2 grams by Eli Lilly & Company. Sales of Merck products using crystalline vitamin B-12 cyanocobalamin, of U.S.P. purity, for the years 1948 through 1964, amounted to $79,575,000.00. It is apparent that vitamin B-12 fulfilled a long felt need for a medicine of great benefit to mankind, a medicine that could now be produced in adequate quantities by fermentation processes under man controlled conditions. It follows, and the Court so finds, that the single claim of the ’794 patent is valid in all respects. Defendants have failed by “convincing evidence” to overcome the presumption of validity to which the patent is entitled under 35 U.S. C.A. § 282. See Moon v. Cabot Shops, Inc., 270 F.2d 539 (9 Cir. 1959); King-Seeley Thermos Co. v. Tastee Freeze Industries, 357 F.2d 875, 879 (7 Cir. 1966). The three product claims of the ’302 patent were involved in earlier litigation. In Merck & Co. v. Olin Mathieson Chemical Corp., 152 F.Supp. 690 (W.D.Va.1957), the District Court found the claims to be invalid as (1) covering a “product of nature”, and (2) for “lack of invention”. On appeal this decision was reversed. The Court of Appeals, in 253 F.2d 156 (4 Cir. 1958) found the claims to be valid, stating: “ * * * We think the invention is meritorious, the product claims of the patent valid and entitled to a liberal construction.” The case was then remanded for further proceedings consistent with the opinion filed by the appellate court. Thereafter, the defendant petitioned the Court of Appeals for a rehearing on the ground that “[t]he defense of double patenting [as against the ’794 patent], pleaded and proved in the District Court, was not passed upon below * * The rehearing was denied, but the court amended its earlier decree “to permit appropriate consideration by the said District Court of any defense except the defense of lack of invention considered and discussed in the opinion of this Court.” In the retrial of the case on remand, the defendant urged the defenses of “double patenting”, “excessive monopoly”, and “non-infringement”. Before a decision was reached on these issues, the case was settled by the taking of a license by the defendant, and the entry of a consent decree. Defendants, in the instant case, gloss over the record in Olin Mathieson, and insist that “new evidence”, and “new connecting evidence”, of “crucial force”, that was not before the courts in the earlier case, establishes the invalidity of the ’302 patent. It is said that on such different evidence as is claimed to be here present, there would be no lack of comity in coming to a conclusion contrary to that reached by the Court of Appeals in Olin Mathieson. That decision is, of course, entitled to great weight on the matters thereby decided, but it has no binding force here. This Court is under a duty to make an independent study of the record in this case and arrive at an independent judgment on the merits. See Standard Brands v. National Grain Yeast Corp., 101 F.2d 814 (3 Cir. 1939). Such a study and determination, in light of the alleged “new evidence”, has been made, and for the reasons hereinafter stated, this Court concludes that the product claims of the ’302 patent are valid. The ’302 patent, as has already been noted, is directed to vitamin B-12 active compositions derived from the fermentation of selected microorganisms. As was stated by the Court of Appeals in Olin Mathieson, the product claims of this patent “ * * * do not reach pure, crystalline vitamin B-12 [the ’794 product], for they are restricted to compositions having a maximum LLD activity which is less than that of the pure substance. The claims do not cover vitamin B-12 compositions derived from liver or any source other than the specified fermentates. Nor do the claims extend to compositions of such low activity as to be of no commercial or therapeutic value. They do cover B-12 active compositions derived from the specified fermentates, which, beyond question, are of very great therapeutic and commercial importance. They are cheaply and abundantly produced and all toxic and harmful substances eliminated without the necessity of isolating crystalline vitamin B-12.” The contention made by defendants that the ’302 patent is invalid because Merck is not entitled, under 35 U.S.C.A. § 120, to invoke the effective filing dates, of the 1948 “parent” applications of