Board of Patent Appeals and Interferences
Patent and Trademark Office (P.T.O.)
*1 EX PARTE LEE R. BECK AND RALPH J. STOLLE
Appeal No. 654-02
September 25, 1987
HEARD: September 21, 1987
Application for Patent filed February 7, 1984, Serial No. 577,804. Heterologous Protein Antibody Formulation For Passive Immunization.
F.D. Vastine et al. for Appellants
Primary Examiner--Blondel Hazel
Before Milestone, Pellman and Winters
Appeal from the examiner's decision refusing to allow claims 1 through 4, 13 through 19, and 25, which are all of the claims remaining in this application.
At the outset, we note that appellants have chosen to argue the patentability of the claims without regard to any particular claim. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979). Thus, all claims on appeal will stand or fall with appealed claim 1 which reads as follows:
1. A method of passively immunizing human beings or a mammalian species, comprising:
parenterally injecting a purified heterologous, natural large molecular weight antibody protein obtained from the serum or milk of a bovid, which has been immunized against an antigenic substance, into a recipient human being or mammalian species having a history of consumption of bovid milk.
The references relied on by the examiner are:
Petersen et al. (Petersen) 3,376,198 Apr. 2, 1968
Singh 3,911,108 Oct. 7, 1975
Joklik et al. (Ed.), Zinsser Microbiology
(New York, Appleton-Century-Crofts)
17th Ed., p. 308
British Patent 1,442,283 Jul. 14, 1976
In the Supplemental Examiner's Answer dated April 27, 1987, which supersedes the first Examiner's Answer in this case dated June 26, 1985, the examiner sets forth the sole remaining grounds of rejection. As stated in the Supplemental Answer, all of the appealed claims stand rejected under 35 USC 103 as unpatentable over either Petersen or Singh.
We shall sustain these rejections.
The Petersen disclosure relates to the production in the mammary glands of ungulates of high specific antibody or protective principle, effective against a wide range of antigens. More particularly, the Petersen invention concerns the production of milk in its natural state fortified with naturally occurring antibodies to preselected antigens.
Petersen discloses that high concentrations of specific antibody in the milk of ungulates (particularly cows, goats, sheep, etc) are produced against any antigen by introducing such antigen into the udder of the animal during the pre-parturition period, that is, during pregnancy. The highest antibody response in the milk results from the introduction of a plurality of doses of increasing amounts of antigen into the udder of an animal in its pre-parturition period over a period of several weeks. Subsequent to parturition, declining antibody concentrations can be increased by periodically introducing booster shots of the selective antigen into the udder during the lactating period.
*2 The antigenic substances which are employed by Petersen for the production of protective principles include, inter alia, bacteria and viruses. Exemplary antigens include Salmonella paratyphi and Staphylococcus aureus, although such materials are merely representative of the almost infinite number and variety of antigenic substances against which specific antibodies or protective principle can be produced in the ungulate udder according to the invention of Petersen. See the reference disclosure, column 3. As disclosed by Petersen, the antigenic substances are suspended in liquid medium for infusion or injection such as, for example, a sterile physiological saline solution. As shown in Example 3 of the reference, Petersen contemplates using a combination of antigenic substances.
Significantly, in the paragraph bridging columns 4 and 5, Petersen discloses that,
The antibody or protective principle which is the product of this invention is useful in a variety of ways. It has been discovered that the protective principle or antibody is absorbed into the system after the milk from stimulated udders has been ingested or administered by proctocylsis. The isolated and separated protective principle may be administered orally, rectally, parenterally and topically. The protective principle is useful in the immunization and treatment of animals. [Emphasis added].
The import of the Singh disclosure is similar to that of Petersen. Specifically, Singh discloses that an enhanced yield of antibodies specific to an antigen is obtained in the milk of a lactating bovine by inoculating the antigen into the mammary gland of a lactating bovine on at least two consecutive days at intervals during the lactation period, the bovine having first been inoculated with the antigen either during its dry prepartum period or during the 24 hour period after parturition.
As with Petersen, the antigens which may be employed in the practice of the Singh invention vary substantially in number and variety. Potentially useful antigens include, inter alia, bacteria and viruses. A specifically named antigen is the Escherichia coli bacteria. See Singh, column 7, line 66.
Significantly, in column 13, lines 8 through 23, Singh discloses that,
The immune milk products may be used to assist in preventing or curing diseases caused by the organism from which the antigen has been derived. It is envisoned that they will be especially effective in helping to control enteric diseases where the causative agents propagate in the digestive tract. In such diseases, the immune milk products can be fed to threatened or sick animals to help in the prevention or cure of the disease in a feed or liquid supplement in a manner analogous to that now used for antibiotics. In respiratory diseases, the more purified products, such as the gamma globulin fraction, may be administered in a suitable biological solution in atomized form to threatened or infected areas. For systemic diseases such purified immune milk fractions may best be administered parenterally in suitable biological dispersing mediums. [Emphasis added].
*3 We agree with the examiner that a person having ordinary skill in the art, armed with either of those prior art disclosures, would have arrived at appellants' claimed method which we hold to be obvious within the meaning of 35 USC 103. In fact, each reference relied on by the examiner expressly discloses a method of passively immunizing an animal by parenterally injecting a purified, heterologous antibody protein obtained from the milk of a bovid, which has been immunized against an antigenic substance, into the recipient animal.
With respect to appellants' claim limitation that the recipient has "a history of consumption of bovid milk", we make the following observations.
First, Petersen and Singh each suggests administering antibody or "protective principle" to a wide variety of animals, including humans. Note particularly column 6 of Petersen, disclosing that "protection from ragweed pollen is offered by consumption of milk with a high protective principle against ragweed pollen." Quite clearly, such reference to producing a protective principle against an allergen is suggestive of a human recipient and, as appellants acknowledge in their specification, page 8, the majority of humans in developed countries drink bovid milk. On these facts, where the prior art references suggest a human recipient and where appellants acknowledge that "the majority of human beings in developed countries drink bovid milk", we have no doubt that the skilled artisan would have arrived at appellants' claimed method.
Second, we note that appellants' claims embrace not only a human recipient but also other mammalian species "having a history of consumption of bovid milk". In this regard, the prior art references to Petersen and Singh disclose the administration of antibody to pigs or baby pigs. According to appellants, pigs "are not commonly fed milk as a routine portion of their diet". See the Reply Brief, page 4. However, we point out that it is not uncommon in farming to feed pigs any available, excess nutrient including excess milk which would otherwise be wasted. We take official notice of that fact. Viewing the situation in this light, we again have no doubt that the artisan would have arrived at appellants' claimed method where the "mammalian species having a history of consumption of bovid milk" is, for example, a pig or baby pig.
Third, with respect to a human recipient, it is common knowledge that many people are allergic to or otherwise react adversely to milk and milk products. We take official notice of that fact. Clearly, the artisan would have viewed those people as singularly inappropriate recipients for the milk products and isolated "protective principle" disclosed by Petersen and Singh. By the same token, the artisan would have expected an improved response from individuals who routinely drink milk without an adverse effect. It cannot be gainsaid, as discussed above, that the cited references suggest human recipients. See, for example, the discussion in Petersen, column 6. We think that it is only a matter of common sense and sound judgment, in selecting a human from the class of recipients suggested by the prior art references, that the artisan would have selected a human "having a history of consumption of bovid milk". In this regard, taking into account the appropriate level of skill in this art, we presume that a person having ordinary skill would exercise common sense and sound judgment. In re Sovish, 769 F.2d 738, 226 USPQ 771 (Fed.Cir.1985).
*4 We therefore conclude that the claim limitation of a recipient "having a history of consumption of bovid milk" cannot serve to patentably distinguish the appealed claims over Petersen or Singh.
Appellants refer to page 308 of Zinsser's Microbiology and page 1 of British Patent 1,442,283 as foundation for their argument that "if one attempts to passively immunize a subject by parenterally injecting the subject with heterologous antibodies, there is the ever present danger of anaphylactic [shock] occurring." See the main Brief, pages 16 through 17 and the Reply Brief, page 6. We have carefully reviewed this argument and the references relied on by appellants, but we remain of the firm conviction that Petersen and Singh would have led the skilled artisan to appellants' claimed method with a reasonable expectation of success. In this regard, we find that Petersen and Singh provide a sufficient basis for the necessary predictability of success to here sustain a rejection under 35 USC 103. In re Clinton, 527 F.2d 1226, 188 USPQ 365 (CCPA 1976). Only a reasonable expectation of success, not absolute predictability, is necessary for a conclusion of obviousness. In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed.Cir.1985).
Appellants further rely on Examples 1 and 2 in their specification disclosure as showing unexpectedly superior results in this case. We find, however, that such reliance is misplaced. It is a basic requirement that comparative evidence, to be effective, must compare the claimed subject matter with the closest prior art. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979). Here, Examples 1 and 2 in the specification are manifestly not designed to compare and do not compare the claimed subject matter with the closest prior art. Accordingly, we find that Examples 1 and 2 do not address the thrust of the examiner's rejection.
In conclusion, we have evaluated and weighed all the evidence in this case, including the prior art references relied on by both the examiner and the appellants and Examples 1 and 2 in appellants' specification disclosure. In re Piasecki, 745 F.2d 1468, 223 USPQ 785 (Fed.Cir.1984); In re Rinehart, 531 F.2d 1048, 189 USPQ 143 (CCPA 1976). It is our judgment that the evidence of obviousness here outweighs the evidence of non-obviousness.
Finally, with respect to the appealed claims, we make the following points: (1) appealed claim 25 appears redundant with claim 2; (2) apparently, claim 13, line 5 is redundant in reciting "gamma globulin IgG antibody" and (3) claim 15 is redundant in twice reciting the bacteria Escherichia coli. However, in view of our disposition of this case, we decline to enter a new ground of rejection under 37 CFR 1.196(b) based on the foregoing points.
*5 For the reasons stated above and those set forth in the examiner's Supplemental Answer, the examiner's decision refusing to allow claims 1 through 4, 13 through 19 and 25 is affirmed.
BOARD OF PATENT APPEALS AND INTERFERENCES
Gordon K. Milestone
Irving R. Pellman
Sherman D. Winters