Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claims 72 has been added.
Claims 1-5, 20-32, 36-46, and 72 are pending.
Claims 6-19, 33-35, and 47-71 are cancelled.
Claims 20-32 and 36-46 are withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, 4 and 5 are rejected under 35 U.S.C. 103 as obvious over CELLIS (WO 2016/207257 A1) in view of BANJERJEE (Faster heme loss from hemoglobin E than HbS, in acidic pH: Effect of aminophospholipids. Journal of Bioscience. 2011.) and REIS (Protein Ultrafilteration. Encyclopedia of Industrial Biotechnology: Bioprocess, Bioseparation, and Cell Technology. 2010.).
With respect to claim 1 and 5, CELLIS teaches pharmaceutical composition comprising various iron binding complexes, such as a hemoglobin-haptoglobin complex (claim 10). The iron binding complex are beneficial due to the ability to encapsulate drugs (Page 34, paragraph 2). CELLIS further teaches that apo-hemoglobin, hemoglobin that has the heme removed, is beneficial for use in drug delivery due to its capability of hosting several hydrophobic molecules within the empty heme pocket (Page 20, paragraph 3). The heme can be displaced by the pocket and be replaced by drugs linked to the complex by proteins (page 35, paragraph 2), such as transferrin (Page 19, paragraph 3).
CELLIS does not have an example that has the apohemoglobin with haptoglobin. However, from CELLIS teaching, all that is needed is swapping hemoglobin for apo-hemoglobin in the hemoglobin-haptoglobin complex.
BANERJEE teaches that it is common in the art to measure the loss of heme from hemoglobin at an absorption of 415 nm, also called the Soret peak (page 811, paragraph 4). The wavelengths of maximum absorption for various hemoglobins going through heme loss (page 810, paragraph 1), at a pH of 4 one of the hemoglobins has a maximum absorption of roughly 412 (figure 1).
REIS teaches that ultrafiltration is commonly used to purify proteins (introduction) and can be optimized using various its various aspects to achieve the desired purification factor (page 18, paragraph 1).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate an absorption of 415 nm. The person of ordinary skill in the art would have been motivated to make those modifications, because it is common to measure the loss of heme from hemoglobin (which would create apohemoglobin) at a Soret peak of 412 nm, and reasonably would have expected success because the references are in the same field of endeavor such as apohemoglobin.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using an ultrafiltration method to purify the apohemoglobin. The person of ordinary skill in the art would have been motivated to make those modifications it can be optimized to achieve the desired level of purification and reasonably would have expected success because it is a common method used in the art to purify proteins.
CELLIS does not specifically teach the weight ratio of apohemoglobin-haptoglobin as claimed by the Applicant. The weight ratio is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal weight ratio in order to best achieve desired results, such as the desired amount of drug binding. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the weight ratio would have been obvious at the time of Applicant’s invention.
Claims 1-5 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over CELLIS (WO 2016/207257 A1) in view of DALTON (US 2009/0281282 A1). CELLIS teaches Applicant’s invention above.
CELLIS does not teach the molecular weight of haptoglobin.
DALTON teaches a haptoglobin pharmaceutical composition. DALTON teaches that haptoglobin has various phenotypes that can be used in pharmaceutical compositions (Page 1, paragraph 0005). One phenotype, Hp 1-1 has a molecule weight of 100 kDa or 165 kDa when complexed with hemoglobin (Page 1, paragraph 0005). DALTON only mentions the Hp 1-1 is complexed with hemoglobin (Page 1, paragraph 0005). It is also noted that the average MW of haptoglobin ranges from 4—95O kDa.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate the molecular weight of haptoglobin. The person of ordinary skill in the art would have been motivated to make those modifications, because the phenotypes are readily available and can be chosen for the particular composition being created, and reasonably would have expected success because the references are in the same field of endeavor, such as hemoglobin- haptoglobin complexes.
Response to Arguments
Applicant argues that references fail to teach a maximum absorption at 411-417 nm as recited by amended claim 1.
Examiner does not find the argument persuasive because as discussed above it is common in the art to measure the loss of heme from hemoglobin at an absorption of 415 nm, also called the Soret peak.
Applicant argues that CELLIS fails to teach apohemoglobin prepared by the ultrafiltration methods described in the specification.
Examiner does not find the argument persuasive because the claims are towards a composition and not towards a method of making. Furthermore, as discussed above, ultrafiltration is commonly used to purify proteins and can be optimized using various its various aspects to achieve the desired purification factor.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/S.L.M./ Examiner, Art Unit 1618
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618