
    357 F. 2d 998; 149 USPQ 44
    In re Philip M. Carabateas
    (No. 7476)
    
    United States Court of Customs and Patent Appeals,
    March 24, 1966
    
      Lcmrence and Laurence (Dean Laurence, Herbert I. Sherman, of counsel) for appellant.
    
      Clarence W. Moore (J. M. Armore, of counsel) for the Commissioner of Patents.
    [Oral argument October 8, 1965, by Mr. Laurence and Mr. Armore]
    Before Worley, Chief Judge, and Rich, Martin, Smith, and Almond, Jr., Associate Judges
    
      
      Petition for rebearing denied May 5, 19G6.
    
   Worley, Chief Judge,

delivered the opinion of the court:

This appeal is from the decision of the Board of Appeals affirming examiner’s rejection of claims 1 and 2 in appellant’s patent application for “4-aryl-4- (lower acyloxy)-l-(3-aryl-3-hydroxypropyl)-piperidines and their preparation.” Appellant has withdrawn appeal of claim 2.

The appealed subject matter is represented by the chemical compound of claim 1:

1. 1- (3-Hydroxy-3-phenylpropyl) -4-phenyl-4-propionoxy-piperidine.

That compound has the structural formula

and is useful as an analgesic.

The references are:

Elpern. II_ 2,846,437 Aug. 5, 1958.
Elpern I_ 2,850,500 Sept. 2, 1958.
Pohland II_ 2,904,550 Sept. 15, 1959.
Pohland I_ 2,951,080 Aug. 30, 1960.
Cutler etal_ 2,962,501 Nov. 29, 1960.

The disclosure of those references was reviewed by this court in In re Carabateas, 52 CCPA 1386, 345 F. 2d 1013, 145 USPQ 549, 551-3, and need not he further detailed here beyond noting that Cutler and Pohland I disclose an analgesic of the structural formula

The examiner found appellant’s piperidinol ester obvious from a consideration of the Cutler, Elpern and Pohland patents, employing reasoning similar to that used by the examiner in Garabateas.

Appellant contends that an affidavit showing the compound of claim 1 to be nineteen times more active as an analgesic than the “reverse ester” compound of Cutler and Pohland I when administered subcutaneously is persuasive evidence of unobviousness and patentability of the compound. As reference to our decision in Garabateas will establish, we thought the Elpern patents collectively suggested that 'piperidinol esters having the structure of appellant’s compounds there claimed would possess greater analgesic activity, perhaps twice as great, than the “reverse esters” which Cutler obtained from the requisite piperidine carboxylic acid. We also referred to a Braenden publication in that record, not relied on by the examiner in Ms rejection, which showed that in changing from the carboxylate structure of O meperidine (ring — &—O—C2H5), to the “reverse” structure (ring— O O — 0—C2H5), the substituent being in the 4-position of the ring, and the remainder of the molecule being kept the same, a five to ten-fold increase in analgesic activity is observed.

We have re-examined the Elpern references on which heavy reliance was placed in our original Garabateas opinion. While we are of the view that those references, together with Cutler, collectively establish obviousness of the structural formula and analgesic activity both of appellant’s compounds claimed there and the present compound, we think we erroneously concluded in Garabateas that the Elpern patents would suggest to one of ordinary skill that any improvement in analgesic activity would necessarily inhere in compounds derived from piperi-dinol, ring — O—C—C2H5, when compared to otherwise identical compounds of the carboxylate structure, ring —C—O—C2H4.

is more potent than the analgesic meperidine, having the formula
The Braenden reference is not in the present record.

In the absence of a suggestion in the present record that the nature of appellant’s improvement would be expected, we think appellant has presented clear and convincing evidence of the greater effectiveness of the claimed compound over the prior art, sufficient here to establish patentability of the compound. In re Lohr, 50 CCPA 1274, 315 F. 2d 338, 137 USPQ 548. Under the circumstances, we think the record fails to support a finding that the subject matter as a whole would be obvious to one of ordinary skill in the art.

The decision of the board is reversed.

High, Judge,

concurring.

I am satisfied this is a clear case for reversal, but for reasons other than those stated by the majority.

While I agree that the art of record collectively establishes obviousness of the structural formula and analgesic activity of the compound defined by the claim on appeal, I am unable to agree that a finding of an improvement in activity in esters of the type here involved, obtained from piperidinols, compared to those obtained from piperi-dine carboxylic acids, would be wholly unexpected to one of ordinary skill in the art with those references before him. To conclude otherwise, it seems to me, is to deny the realities of the situation; for the plain fact is that, without exception, the Elpern II compounds demonstrate potency greater than that possessed by the Elpern I compounds. While those compounds differ structurally in two respects, there is no reason to believe that either is not responsible, at least in part, for that increase in activity.

I would therefore reverse on what to me is a much sounder basis, both in law and on the facts presented, namely that the art makes no suggestion whatever that a reversal of the ester linkage would result in an increased activity approximately the nineteen-fold increase found by appellant. At the very best, the art suggests an increase of the order of four to eight times. This is a far cry from what appellant found.

The question is not, it seems to me, whether the art suggests an improvement, but rather whether it reasonably suggests the particu lar improvement relied upon for patentability in both its qualitative and qualitative sense. See In re Lunsford (P.A. 7478), decided March 17, 1966, 53 CCPA 986, 357 F. 2d 380, 148 USPQ 716. As in all section 103 cases, the important consideration is: does the prior art make obvious to those of ordinary skill what appellant has found? 
      
       Serial No. 85,195, filed January 27, 1961.
     
      
       That figure was established by a finding that appellant’s compound and that of Cutler were 3220 times and 173 times, respectively, more potent than meperidine, a well known analgesic, on a molar basis.
     
      
       That appears consistent with the discussion in In re Lunsford, 51 CCPA 1000, 327 F. 2d 526, 140 USPQ 425, wherein it was observed that the analgesic prodine, having the formula
     
      
       We said in Garabateas:
      
      Referring to the Elpern patents, it will be seen that the Elpern XX “l-( 3-phenoxy-propyl)-4-acetoxy” compound, which has the same sort of ester structure as appellant’s compounds, possesses twice the analgesic activity of the Elpern I ethyl (3-phenoxypropyl) piperidine-4-carboxylate. Compared with the Elpern I ethyl (2-phenoxyef7ti/Z) piperidine-4-carboxylate and ethyl (4-phenoxy6wt2/Z) piperidine-4-carboxylate esters, this same Elpern II compound, albeit not the exact “reverse ester” but instead a homolog thereof, is, respectively, four and eight times more effective as an analgesic. We believe this amply suggests that esters having the structure of ■appellant’s compounds will possess greater analgesic activity than their “reverse /esters.”
      In drawing that conclusion, we assumed that the “4-acetoxy” compound of Elpern II was identical to (e.g. the exact “reverse ester”) the ethyl-4-carboxylate compound of Elpern I but for reversal of the ester linkage. In fact it is not, as comparison of the respective structures (ring — 0—C—CH3 vis a vis ring — C—O—C„H5) demonstrates. We think such a 5 A comparison of ester homologues to be too tenuous to suggest that any improvement would be obtained solely because of reversal of the ester linkage. That comparison being the controlling evidence in Garabateas, we think the decision there rendered necessarily is incorrect.
     