Notice of Pre-AIA or AIA Status
For reissue applications filed before September 16, 2012, all references to 35 U.S.C. 251 and 37 CFR 1.172, 1.175, and 3.73 are to the law and rules in effect on September 15, 2012. Where specifically designated, these are “pre-AlA” provisions.
For reissue applications filed on or after September 16, 2012, all references to 35 U.S.C. 251 and 37 CFR 1.172, 1.175, and 3.73 are to the current provisions.
The present application is being examined under the pre-AlA first to invent
provisions.
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. The amendments filed on 05/12/2026 have been entered.
Status of the Claims
On 4/26/2011 US Patent 7,932,365 issued to Lim et al. with claims 1-25.
The amendments and arguments filed 05/12/2026 are acknowledged and have been fully considered. Claims 1-38 have been cancelled. Claims 39 and 41-54 are now pending, and are new relative to the ‘365 patent. Claims 39 and 41-54 are now under consideration.
This Office Action is in response to the request for continued examination filed on 05/12/2026.
Defective Declaration/Oath
The reissue oath/declaration filed with this application is defective because it fails to identify at least one error which is relied upon to support the reissue application. See 37 CFR 1.175 and MPEP § 1414.
The error statement in the declaration filed 01/14/2026 no longer applies because it referred to amended claim 13 as a broader claim than issued claim 13. However, claim 13 has been cancelled, so the error statement is no longer accurate.
CLAIM REJECTIONS - 35 USC § 251
Claims 39 and 41-54 are rejected as being based upon a defective reissue declaration under 35 U.S.C. 251 as set forth above. See 37 CFR 1.175.
The nature of the defect(s) in the declaration is set forth in the discussion above in this Office Action.
OBJECTIONS/REJECTIONS WITHDRAWN
The rejections of claims 13-16, 28-30, 32, and 34-39 under 35 U.S.C. 103(a) are moot in light of the claim amendments.
NEW GROUNDS OF REJECTION
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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 under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 39 and 41-53 are rejected under 35 U.S.C. 103(a) as being unpatentable over JOSIC (WO 02/30983; Pub. Apr. 18, 2002 or US 2003/0190732; Filed Oct. 11, 2001) and WISNIEWSKI (US 6,313,091; Issued Nov. 6, 2001).
Since WO 02/30983 is in German, US patent application publication 2003/0190732 to Josic, which is the national stage entry of the international application, is relied upon as an English language equivalent for WO 02/30983. Paragraph numbers refer to the '732 publication.
Josic discloses a method of producing bikunin proteins from plasma (e.g., human plasma) (title; abstract; [0006], [0009]). The purified plasma fraction contains bikunin-containing proteins of apparent molecular weight of 100 to 250 kDa, such as inter-α-inhibitor (IαI; MW 220 kDa) and pre-α-inhibitor (PαI; MW of at least 100 kDa) ([0002], [0006], [0026]). The purified plasma fraction of Josic is employed as the base of a pharmaceutical formulation, which is obtainable by the optional further purification of the bikunin proteins and by formulation, and by measures for sterilization or sterile filtration and by inactivation of any pathogens present ([0027]). Josic teaches the formulation is suitable for intravenous administration (i.e., suitable for administration to a human) ([0027]).
The purified IαI and PαI of the plasma fraction would be in physiological proportion when they are purified from plasma, where they occur naturally. While Josic is silent on the proportions of the two proteins in the composition, Josic teaches that these proteins can be isolated directly from plasma or from cryosupernatant ([0009]); therefore each contains the proteins in physiological proportions as it occurs naturally in human plasma. It is noted that the specification states that physiological proportions are usually between about 60-80% IαI and about 40-20% PαI, but that physiological proportions vary between subjects (col. 5, lines 8-12). The person of ordinary skill in the art would therefore have understood Josic’s teachings as disclosing the claimed proportions.
Josic teaches the use of the disclosed pharmaceutical composition comprising purified lal and Pal for treating sepsis or septic shock ([0008], [0031]; claim 13). Sepsis and septic shock are the result of an infection (i.e., an infectious disease). Thus, one treating sepsis or septic shock would necessarily be treating an infectious disease within the meaning of the instant claims.
Regarding the amount of the IαIp administered, Josic teaches the therapeutic dosage is in the range from 3-300 mg/kg ([0030]). This teaching overlaps the claimed amount of 1-50 mg per kg body weight.
While Josic teaches the use of the purified plasma fraction as the base of a pharmaceutical formulation in combination with excipients such as stabilizers ([0027]-[0028]), Josic does not expressly teach the amount of IαIps in terms of percentage of the composition as instantly recited. However, one of skill in the art would find it obvious to use an amount of active agent within the broad range (i.e., 5-95%) instantly claimed.
For example, Wisniewski discloses compositions for treating inflammatory diseases such as sepsis and infectious diseases (title; abstract; col. 5, lines 61-67). The compositions may comprise IαI and PαI proteins (col. 2, lines 24-63; col. 14, lines 28-32; Examples). Wisniewski teaches that pharmaceutical compositions contain from 0.01-99%, preferably about 20-75% of the active component (col. 15, lines 36-39).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art to have used the IαIps of Josic in an amount of 20-75% of the pharmaceutical composition. One would have been motivated to do so since this range is known in the art to be suitable for active agents, with the remainder of the composition being excipients for formulating the active as desired.
Regarding claims 41-42, Josic teaches the anti-trypsin specific activity, which is an intrinsic property of the bikunin-containing proteins, is much higher in the bikunin plasma fraction than the activity of human plasma. The anti-trypsin specific activity is preferably more than 200 times that in human plasma ([0023]-[0024]), which encompasses the claimed trypsin inhibitory specific activity of about 1000 to about 2000 IU/mg or about 1400 to about 2000 IU/mg ([0024]; claim 8). Furthermore, specific activity is simply a measure of protein purity, and the compositions of Josic are taught to have purity within the range instantly claimed ([0023]; claim 7).
Regarding claim 43, Josic teaches that the bikunin in the purified plasma fraction has a half-life of several hours in vivo ([0007]). This teaching is greater than one hour as recited in claim 43.
Regarding claims 44-45, these claims require that the half-life of the composition is at least 5 hours or at least 10 hours, respectively. Josic teaches that the bikunin in the purified plasma fraction has a half-life of several hours in vivo ([0007]), and renders obvious the half-lives recited in claims 44-45. Although Josic does not limit the term “several hours,” the person of ordinary skill in the art would have interpreted it as reasonably encompassing times such as 5-10 hours. Thus, “several hours” is reasonably considered to disclose a half-life of “at least 5 hours” and “at least 10 hours.”
In the alternative, however, if “several hours” does not render obvious these time ranges directly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close (MPEP 2144.05). In this case, there is no indication that there are any structural differences between the compositions of Josic and those of the instant claims.
Finally regarding claims 44-45, the instant specification teaches that half-life is an inherent property of the composition and fluctuations of the half-life are not based on the structure of the composition itself, but rather on the state of sepsis (i.e., the rate of clearance) in the patient to which the composition is administered (see col. 20, lines 1-6; col. 20, line 60 to col. 21, line 12; col. 21, lines 37-41; Fig. 4 of the '365 patent). Thus, in the absence of any structural difference between the compositions of Josic and those instantly claimed, the half-life is considered a property of the composition that depends upon the disease state at a given time.
Regarding claim 46, Josic teaches that the pharmaceutical formulations are suitable for intravenous administration (i.e., they are suitable for administration to a human) ([0027]-[0028]). The liquid base of said intravenous formulation that is necessarily present is within the broadest reasonable interpretation of a pharmaceutically acceptable carrier. Moreover, Wisniewski teaches the use of carriers (col. 4, lines 3-6; col. 15, lines 17-24).
Regarding claim 47, the process disclosed by Josic results in pure IαI and PαI proteins that do not have any additional substantial components, and are essentially free of unbound separate bikunin ([0006]; [0025]-[0026]). The purified plasma fraction of Josic contains at least 90% proteins that exhibit anti-trypsin activity, indicating that the proteins are within the scope of about 90% to 100% pure (i.e., about 90% pure) ([0023]; claim 7).
Regarding claims 49-50, Josic teaches the purified plasma fraction of bikunin (light chain), contains proteins associated with at least one heavy chain selected from H1, H2 and H3 ([0001], [0003], [0006]).
Regarding claims 51-52, Josic teaches adding a stabilizer such as polyols, sugars, sugar alcohols, amino acids, or inorganic salts to the bikunin plasma fraction composition ([0027]-[0028]).
Regarding claim 53, Wisniewski teaches the additional use of TSG-6 as a therapeutic agent (col. 14, lines 28-32).
Claim 54 is rejected under 35 U.S.C. 103(a) as being unpatentable over JOSIC (WO 02/30983; Pub. Apr. 18, 2002 or US 2003/0190732; Filed Oct. 11, 2001) and WISNIEWSKI (US 6,313,091; Issued Nov. 6, 2001) as applied to claims 39 and 41-53 above, and further in view of FISHER (US 2001/0006806; Pub. Jul. 5, 2001) as evidenced by JOYCE (Joyce, D. E., et al. Crit. Care Med. (2002), 30(5); S288-S293).
The teachings of Josic and Wisniewski are presented supra, and are incorporated herein. Josic does not teach a composition further comprising an immunomodulator as an additional therapeutic agent as recited in claim 54.
Fisher discloses methods for treating sepsis including combination therapy with protein C, which is taught to have anti-coagulant and anti-inflammatory properties (i.e., it is an anti-coagulant and an anti-inflammatory) (title; abstract; [0003], [0017]). Protein C also has immunomodulatory properties (i.e., it is an immunomodulator within the meaning of the instant claims) as evidenced by Joyce (see p. S292, middle col.).
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to prepare a pharmaceutical composition comprising purified IαI and PαI in (in their physiological proportions) in combination with an anticoagulant/anti-inflammatory/immunomodulator such as protein C. One would have been motivated to do so since all of these compounds are known in the art to treat sepsis (i.e., infectious disease as discussed above). The MPEP states: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP § 2144.06(I).
Claim 54 is rejected under 35 U.S.C. 103(a) as being unpatentable over JOSIC (WO 02/30983; Pub. Apr. 18, 2002 or US 2003/0190732; Filed Oct. 11, 2001) and WISNIEWSKI (US 6,313,091; Issued Nov. 6, 2001) as applied to claims 39 and 41-53 above, and further in view of MacFARLANE (US 6,479,504; Pub. Nov. 12, 2002).
The teachings of Josic and Wisniewski are presented supra, and are incorporated herein.
Josic teaches a pharmaceutical composition comprising purified lal and Pal, which can be used to treat sepsis. Josic does not teach a composition further comprising an immunomodulator as an additional therapeutic agent as recited in claim 54.
MacFarlane discloses methods inhibiting stimulation of the immune system with 4-aminoquinoline chloroquine analogues (title, abstract). MacFarlane teaches excessive stimulation of the immune system can have adverse effects in autoimmune diseases, rejection during transplantation, and invasions by pathogens. Inhibition of this stimulation can have beneficial therapeutic results (col. 1, lines 19-27). MacFarlane teaches sepsis is the primary cause of death in intensive care units in the United States annually. It can be caused by infection by a pathogen, such as viruses, bacteria, fungi, and parasites (i.e., infectious diseases), which triggers host defenses. This may result in activation of innate immunity, particularly, an inflammatory response, which consequently promotes deleterious effects (collectively termed "sepsis") including shock, respiratory distress, capillary leaks, renal failure, jaundice, bleeding, coma and death (col. 2, lines 14-22). MacFarlane teaches use of the disclosed 4-aminoquinolines for the treatment of sepsis (col. 2, lines 37-41; col. 12, lines 16-20; col. 13, lines 47-53; col. 14, lines 40-52). Because the compounds of MacFarlane affect the immune response (i.e., they suppress excessive immune stimulation), they are immunomodulators within the meaning of the instant claims.
In light of these teachings, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to prepare a pharmaceutical composition comprising IαI and PαI (in their physiological proportions) in combination with an immunomodulator. One would have been motivated to do so since all of these compounds are known in the art to treat sepsis and septic shock (i.e., infectious disease as discussed above). The MPEP states: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP § 2144.06(I).
Response to Arguments
Applicants' arguments have been fully considered but are not persuasive. Applicants argue that the claims have been amended to now recite a method of treating certain conditions.
The new grounds of rejection presented in this Office Action address the new and amended claims, which are obvious as discussed above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
US Patent RE 47,972
Claims 39 and 41-54 are non-provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 26-40 of US Patent RE 47,972. Although the conflicting claims are not identical, they are not patentably distinct from each other because the scope of the '972 claims anticipates or renders obvious that of the instant claims. The difference between the two claim sets is that the '972 claims recite a timeframe for administration. However, the instant claims are generic to a timeframe for administration, and are thus anticipated by the '972 claims.
Conclusion
Claims 39 and 41-54 are rejected. No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kevin S Orwig whose telephone number is (571)270-5869. The examiner can normally be reached Mon.-Fri. 7AM-4PM (with alternate Fridays off). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Patricia Engle can be reached Mon.-Fri. at (571)276660. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Kevin S Orwig/ Patent Reexamination Specialist, Art Unit 3991
Conferees:
/LBD/ Patent Reexamination Specialist, Art Unit 3991
/Patricia L Engle/ SPRS, Art Unit 3991
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