DETAILED ACTION
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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-13, 20, 22, and 24-26 in the reply filed on 05/22/2026 is acknowledged.
Claims 14-15 and 17 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/22/2026.
Status of the Claims
Claims 2-5, 11, and 13-23 have been cancelled. New claims 27-29 have been added.
Claims 1, 6-10, 12 and 24-29 are pending and currently under examination.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been received and placed in the file.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
Initialed and dated copies of Applicants’ information disclosure statements (IDS) filed on 11/20/2023 is attached to the instant Office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Objections
Claims 6-10, 12, and 24-26 objected to because of the following informalities: The dependent claims 6-10, 12, and 24-26 lack the article “The” at the beginning of each claim. The examiner suggest that the applicant recites the definite article “the” at the beginning of the claims. See MPEP 608.01(n)(IV). Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact 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, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact 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, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 1, 6-10, and 24-29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for reducing the risk of post-operative complications in a subject, does not reasonably provide enablement for a method for preventing the risk of post-operative complications in a subject.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)). These include:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based
on the content of the disclosure
All of the Wands factors have been considered with regard to the instant claims,
as discussed below:
The breadth of the claims/(B) The nature of the invention:
The claims are directed towards a method for preventing the risk of post-operative complications in a subject by administering to the subject a therapeutically effective amount of a zinc delivery agent, wherein the zinc delivery agent comprises a zinc ion and at least one amino acid or a salt thereof. The scope of the phrase “post-operative complications” is enormous. The claims place no limitation on the identity of the “post-operative complications”.
(C) The state of the prior art/(E) The level of predictability in the art:
In order to use the invention, as claimed, one having ordinary skill in the art would need to identify the full scope of post-operative complications that can be treated by the administration of a zinc delivery agent. With regards to the post operative complications, at the time of the instant invention the skilled Artisan would at first need to identify every possible post operative complication. Lowth teaches Doctors are aware of the risk of complications and take steps before, during and after surgery to reduce this risk. However, some complications are common and occur frequently despite precautions. Some postoperative complications are related to the exact surgery that you have had, but many (such as wound infection) may occur after any kind of surgery (What are postoperative complications section). Lowth also teaches postoperative complications include immediate complications (up to three days after the surgery), early complications (most likely in the few weeks after your surgery) and late complications (up to years afterwards) (When do postoperative complications occur? Section). Lowth list an extensive list of possible postoperative complications. Lowth further teaches that Modern approaches to surgery and anesthetics are very advanced compared to the distant past, and health professionals know a great deal about how to reduce the risk of postoperative complications. However, the risks are still there, even though they are kept as small as possible. Surgery is a serious kind of assault on the body (Can postoperative complications be prevented?, section). Sakornpant teaches Pneumonia and respiratory insufficiency requiring mechanical ventilatory support > 7 days are the two most common complications. The overall complications occurs in 22% of population; in this population, the in-hospital mortality is 21% and the mean postoperative length of stay is 21 days. Of all complications, cardiac arrest, mechanical circulatory support, systemic vein obstruction, acute renal failure requiring temporary dialysis and sternum being left opened carry high in-hospital mortality rate at 75%, 66%, 63%, 59% and 59% in successive order. The higher is the mortality category, the higher is the number of postoperative complication also with very high percentage of in-hospital mortality (Overall postoperative complications section). Sakornpant further teaches a list of post operative complications and in hospital mortality in 26 hospitals. Accordingly it would be difficult for a person of ordinary skill in the art to predict which post operative complications might respond to treatment with a composition comprising a zinc delivery agent.
Finally, MPEP 2164.03 indicates that the physiological art in general is unpredictable. “A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because it is not obvious from the disclosure of one species, what other species will work.”
(D) The level of one of ordinary skill: One having ordinary skill in the art would be an individual possessing an advanced degree in medicine, biomedicine, or pharmaceutical sciences.
(F) The amount of direction provided by the inventor/(G) The existence of working examples:
The instant specification discloses a post-operative complications associated with reduced blood flow and reduced oxygen delivery to tissues, typically neurological and renal complications. Exemplary post-operative neurological complications include delirium. Exemplary post-operative renal complications include acute kidney injury and subsequent chronic kidney disease (paragraph [0014]). The instant specification’s examples are directed to increase in cutaneous blood flow, improvement in renal blood flow, vascular resistance and renal oxygen delivery. The examiner does not consider the post operative complications cited concisely in the specification as well as the working examples to provide enablement for practicing the full scope of the invention as embraced by the phrase “preventing post operative complications”.
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
In view of the foregoing analysis, the examiner concludes that the quantity of experimentation required to practice the full scope of the invention, as claimed, would be undue.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact 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, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact 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, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims1, 6-10, and 24-2 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Specifically, the written description requirement has not been met for the full scope of “post-operative complications”.
Applicant is referred to the Guidelines on Written Description published at FR 66(4) 1099-1111 (January 5, 2001) (also available at www.uspto.gov). The following passage is particularly relevant.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant identifying characteristics, i.e. structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between structure and function, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within a genus, one must describe a sufficient number of species to reflect the variation within the genus. What constitutes a "representative number" is an inverse function of the skill and knowledge in the art. Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed. In an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.
For Example MPEP 2163 states, in part,
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
Claim 1 is drawn to the genus of post-operative complications. This genus embrace any post operative complications which in itself is an enormous genus. Accordingly the breadth of the claims is immense.
As discussed in more detail below, the specification provides inadequate and insufficient examples to show possession of the genus of post operative complications. The specification as filed discloses complications associated with reduced blood flow and reduced oxygen delivery to tissues, typically neurological and renal complications. Exemplary post-operative neurological complications include delirium. Exemplary post-operative renal complications include acute kidney injury and subsequent chronic kidney disease (paragraph [0014]). The instant specification’s examples are directed to increase in cutaneous blood flow, improvement in renal blood flow, vascular resistance and renal oxygen delivery. The examiner does not consider the post operative complications cited concisely in the specification as well as the working examples to provide enablement for practicing the full scope of the invention as embraced by the phrase “preventing post operative complications”.
With regard to the scope of post operative complications embraced by the claims, the specification fails to provide disclosure of relevant identifying characteristics, i.e. structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between structure and function, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Only increase in cutaneous blood flow, improvement in renal blood flow, vascular resistance and renal oxygen delivery by the administration of the zinc delivery agent has been reduced to practice. One having ordinary skill in the art would not be able to identify which post operative complications falling within the immense scope of these terms would exhibit the requisite characteristic based upon the description in the specification and no concrete structural, physical properties, correlation between structure and function, or combination thereof is provided as guidance to sort post operative complications that will respond to treatment with the zinc delivery agent.
With regards to the post operative complications, at the time of the instant invention the skilled Artisan would at first need to identify every possible post operative complication. Lowth teaches doctors are aware of the risk of complications and take steps before, during and after surgery to reduce this risk. However, some complications are common and occur frequently despite precautions. Some postoperative complications are related to the exact surgery that you have had, but many (such as wound infection) may occur after any kind of surgery (What are postoperative complications section). Lowth also teaches postoperative complications include immediate complications (up to three days after the surgery), early complications (most likely in the few weeks after your surgery) and late complications (up to years afterwards) (When do postoperative complications occur? Section). Lowth list an extensive list of possible postoperative complications. Lowth further teaches that Modern approaches to surgery and anesthetics are very advanced compared to the distant past, and health professionals know a great deal about how to reduce the risk of postoperative complications. However, the risks are still there, even though they are kept as small as possible. Surgery is a serious kind of assault on the body (Can postoperative complications be prevented?, section). Sakornpant teaches Pneumonia and respiratory insufficiency requiring mechanical ventilatory support > 7 days are the two most common complications. The overall complications occurs in 22% of population; in this population, the in-hospital mortality is 21% and the mean postoperative length of stay is 21 days. Of all complications, cardiac arrest, mechanical circulatory support, systemic vein obstruction, acute renal failure requiring temporary dialysis and sternum being left opened carry high in-hospital mortality rate at 75%, 66%, 63%, 59% and 59% in successive order. The higher is the mortality category, the higher is the number of postoperative complication also with very high percentage of in-hospital mortality (Overall postoperative complications section). Sakornpant further teaches a list of post operative complications and in hospital mortality in 26 hospitals. Accordingly it would be difficult for a person of ordinary skill in the art to predict which post operative complications might respond to treatment with a composition comprising a zinc delivery agent.
Thus, at the time of the invention it had been established that with regard to post operative complications, in general response to post operative complication treatment strategies is highly unpredictable.
Applicant's attention is also directed to In re Shokal, 113 USPQ 283 (CCPA 1957), wherein it is stated:
It appears to be well settled that a single species can rarely, if ever, afford sufficient support for a generic claim. In re Soll, 25 CCPA (Patents) 1309, 97 F2d 623, 38 USPQ 189; In re Wahlforss, 28 CCPA (Patents) 867, 117 F2d 270, 48 USPQ 397. The decisions do not however fix any definite number of species which will establish completion of a generic invention and it seems evident therefrom that such number will vary, depending on the circumstances of particular cases. Thus, in the case of small genus such as the halogens, consisting of four species, a reduction to practice of three, perhaps even two, might serve to complete the generic invention, while in the case of a genus comprising hundreds of species, a considerably larger number of reductions to practice would probably be necessary.
As stated in MPEP 2163 II: If the application as filed does not disclose the complete structure (or acts of a process) of the claimed invention as a whole, the Examiner must determine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. The instant specification is devoid of a description for the numerous possible neoplastic diseases that respond to therapeutic agents. Thus, Applicants have failed to demonstrate possession thereof. Disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Disclosure of a small list of therapeutic agents does not constitute an adequate description to demonstrate possession of the numerous neoplastic diseases that would respond to the therapeutic agents.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 6-10, 12 and 24-29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “a method for preventing or reducing the risk of post-operative complications”. This language is indefinite because there is no clear way of knowing if the method steps result in treatment or prevention as per the definition provided by the Applicant in the instant specification “Thus the terms "treating" and "preventing" and the like are to be considered in their broadest context. For example, treatment does not necessarily imply that a patient is treated until total recovery” (paragraph [0047]).
Claim 9 recites the limitation "the surgery" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 10 recites the limitation "the surgery" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claims depending from rejected claims have also been rejected because they incorporate all of the limitations of the claims from which they depend, but fail to resolve the indefiniteness concerns outlined above.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 29 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
In this case, claim 29 fail(s) to further limit the subject matter of the claim upon which they depend. The method of claim 28 is interpreted under 35 USC 112 to contain only the recited in the claims (i.e., wherein the zinc delivery agent comprises from about 0.1 mg/kg to about 100 mg/kg zinc bis(histidinate). Thus claim 29 fail(s) to further limit claim 28 because the method of claim 29 is the exact same as claim 28.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 6-9, 12 and 24-29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hegenauer et al. (Journal of Trace Elements in Experimental Medicine, 1991, vol. 4; cited in the IDS filed 11/20/2023).
The claims are drawn to a method for preventing or reducing the risk of post-operative complications in a subject, the method comprising administering to the subject a therapeutically effective amount of a zinc delivery agent, wherein the zinc delivery agent comprises a zinc ion and at least one amino acid or a salt thereof, and wherein the administration of the zinc delivery agent maintains a systemic mean arterial pressure of at least about 50 mmHg.
Regarding claims 1, 6, 12, and 27 Hegenauer discloses the administration of zinc in the form of a 1:2 Zn(II)-histidine complex (i.e., a zinc ion and at least one amino acid or a salt thereof) (page 104 Methods section), to mitigate renal reperfusion injury (i.e., post-operative complication) in rabbit (page 103, abstract) by protecting kidneys against postischemic reperfusion injury (page 104, first paragraph). Hegenauer discloses the administration of Zn(II)-histidine complex (i.e., a zinc ion and at least one amino acid or a salt thereof) to mitigate renal reperfusion injury (i.e., post-operative complication) in rabbit (page 103, abstract), but does not explicitly disclose wherein the administration of the zinc delivery agent maintains a systemic mean arterial pressure; at least about 50 mmHg or of at least about 65 mmHg; wherein the post-operative complication is acute kidney injury or chronic kidney disease; and the method of claim 1 which reduces or eliminates the need for vasopressor support. However, such properties must necessarily be present. Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of the claimed product. See In re Ludtke, 441 F.2d 660, 169 USPQ 563 (CCPA 1971). Whether the rejection is based on "inherency" under 35 USC 102, on "prima facie obviousness" under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, Bolton, and Shaw, 195 USPQ 430, 433 (CCPA 1977) citing In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972).
Regarding claim 7, Hegenauer discloses when the Zn bolus was administered as above 30 min before ischemia (i.e., prior to surgery), renal function was significantly better than that in the untreated group (page 105, Effect of Zn on Kidney Reperfusion injury).
Regarding claims 8, and 28-29, Hegenauer discloses a single intravenous bolus of 30 µmoles of Zn/kg administered over 30 sec was well tolerated by the rabbit. This dose of Zn (~2 mg/kg) may be compared with the daily oral requirement for man (page 105, Metabolism of Intravenous Zn-Histidine).
Regarding 9, Hegenauer discloses that the New Zealand white rabbits abdomen was opened through a midline incision (i.e., abdominal surgery), the right kidney removed and the left renal artery occluded with a noncrushing clamp (i.e., vascular surgery), which was removed following 1 hr of warm ischemia. The abdomen was then closed with a running suture, and the femoral catheter discontinued (page 104, Reperfusion studies).
Regarding claim 24-26, Hegenauer discloses the administration of Zn(II)-histidine complex (i.e., Zinc bis(histidnate)) (i.e., a zinc ion and at least one amino acid or a salt thereof) to mitigate renal reperfusion injury (i.e., post-operative complication) in rabbit (page 103, abstract).
Accordingly, Hegenauer anticipated the claimed invention.
Claim Rejections - 35 USC § 103
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.
Claims 1, 6-9, 12 and 24-29, are rejected under 35 U.S.C. 103 as being unpatentable over Hegenauer et al. (Journal of Trace Elements in Experimental Medicine, 1991, vol. 4; cited in the IDS filed 11/20/2023).
Applicant’s Invention
The claims are drawn to a method for preventing or reducing the risk of post-operative complications in a subject, the method comprising administering to the subject a therapeutically effective amount of a zinc delivery agent, wherein the zinc delivery agent comprises a zinc ion and at least one amino acid or a salt thereof, and wherein the administration of the zinc delivery agent maintains a systemic mean arterial pressure of at least about 50 mmHg.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 1, 6, 12, and 27 Hegenauer teaches the administration of zinc in the form of a 1:2 Zn(II)-histidine complex (i.e., a zinc ion and at least one amino acid or a salt thereof) (page 104 Methods section), to mitigate renal reperfusion injury (i.e., post-operative complication) in rabbit (page 103, abstract) by protecting kidneys against postischemic reperfusion injury (page 104, first paragraph). Hegenauer teaches the administration of Zn(II)-histidine complex (i.e., a zinc ion and at least one amino acid or a salt thereof) to mitigate renal reperfusion injury (i.e., post-operative complication) in rabbit (page 103, abstract), but does not explicitly disclose wherein the administration of the zinc delivery agent maintains a systemic mean arterial pressure; at least about 50 mmHg or of at least about 65 mmHg; wherein the post-operative complication is acute kidney injury or chronic kidney disease; and the method of claim 1 which reduces or eliminates the need for vasopressor support. However, such properties must necessarily be present. Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an Applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of the claimed product. See In re Ludtke, 441 F.2d 660, 169 USPQ 563 (CCPA 1971). Whether the rejection is based on "inherency" under 35 USC 102, on "prima facie obviousness" under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. In re Best, Bolton, and Shaw, 195 USPQ 430, 433 (CCPA 1977) citing In re Brown, 59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972).
Regarding claim 7, Hegenauer teaches when the Zn bolus was administered as above 30 min before ischemia (i.e., prior to surgery), renal function was significantly better than that in the untreated group (page 105, Effect of Zn on Kidney Reperfusion injury).
Regarding claims 8, and 28-29, Hegenauer teaches a single intravenous bolus of 30 µmoles of Zn/kg administered over 30 sec was well tolerated by the rabbit. This dose of Zn (~2 mg/kg) may be compared with the daily oral requirement for man (page 105, Metabolism of Intravenous Zn-Histidine).
Regarding 9, Hegenauer teaches that the New Zealand white rabbits abdomen was opened through a midline incision (i.e., abdominal surgery), the right kidney removed and the left renal artery occluded with a noncrushing clamp (i.e., vascular surgery), which was removed following 1 hr of warm ischemia. The abdomen was then closed with a running suture, and the femoral catheter discontinued (page 104, Reperfusion studies).
Regarding claim 24-26, Hegenauer teaches the administration of Zn(II)-histidine complex (i.e., Zinc bis(histidnate)) (i.e., a zinc ion and at least one amino acid or a salt thereof) to mitigate renal reperfusion injury (i.e., post-operative complication) in rabbit (page 103, abstract).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Hegenauer does not disclose a single embodiment or example where every limitation recited in the instant claims is taught.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
The claims are considered prima facie obvious to one of ordinary skill in the art at the time of filing because Hegenauer teaches all of the claimed elements. It would have been prima facie obvious to one of ordinary skill at the time of filing to have a method for preventing or reducing the risk of post-operative complications in a subject, the method comprising administering to the subject a therapeutically effective amount of a zinc delivery agent, wherein the zinc delivery agent comprises a zinc ion and at least one amino acid or a salt thereof, and wherein the administration of the zinc delivery agent maintains a systemic mean arterial pressure of at least about 50 mmHg because Hegenauer teaches and contemplates all the elements required to do the method.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Hegenauer et al. (Journal of Trace Elements in Experimental Medicine, 1991, vol. 4; cited in the IDS filed 11/20/2023) as applied to claims 1, 6-9, 12 and 24-29 above, and further in view of Axtell et al. (J Thorac Cardiovasc Surg. 2020 Jan;159(1):170-178)
Applicant’s Invention
Hegenauer renders obvious all the limitations of instant claim 1. Applicant’s claim 10 further adds the limitation wherein the surgery is cardiac surgery requiring cardiopulmonary bypass.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regrading claim 10, Hegenauer teaches the administration of zinc in the form of a 1:2 Zn(II)-histidine complex (i.e., a zinc ion and at least one amino acid or a salt thereof) (page 104 Methods section), to mitigate renal reperfusion injury (i.e., post-operative complication) in rabbit (page 103, abstract) by protecting kidneys against postischemic reperfusion injury (page 104, first paragraph).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Hegenauer does not teach wherein the surgery is cardiac surgery requiring cardiopulmonary bypass. However this deficiency is cured by Axtell et al.
In the analogous art of renal injury, Axtell teaches acute renal failure (ARF)is recognized as a highly morbid complication after cardiac surgery associated with increased resource utilization and mortality rates as high as 60% following coronary artery bypass graft (page 170, first paragraph). Axtell also teaches multiple prior studies have identified risk factors associated with postoperative ARF, of which prolonged cardio pulmonary bypass (CPB) time is frequently cited (page 108, second paragraph). Axtell further teaches several pathophysiologic mechanisms have been proposed for renal injury during CPB including perioperative renal ischemia and reperfusion injury, CPB-induced hemolysis and pigment nephropathy, oxidative stress, and systemic inflammation (page 177, second paragraph). Axtell continues to teach finally, cardiac surgery has been shown to increase both renal and systemic inflammation with ischemia and reperfusion as well as erythrocyte hemolysis inducing production of reactive oxygen species, which in turn upregulate proinflammatory transcription factors, cytokines, and chemokines. The cumulative and synergist effect of these mechanisms over time likely contribute to the increased risk of renal injury seen with increasing CPB duration (page 177, second paragraph).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to use Hegenauer’s method of mitigating renal reperfusion injury wherein the surgery is cardiac surgery requiring cardiopulmonary bypass. Hegenauer teaches administration of zinc in the form of a 1:2 Zn(II)-histidine complex (i.e., a zinc ion and at least one amino acid or a salt thereof) (page 104 Methods section), to mitigate renal reperfusion injury (i.e., post-operative complication) in rabbit (page 103, abstract) by protecting kidneys against postischemic reperfusion injury (page 104, first paragraph). One would have understood in view of Axtell that multiple prior studies have identified risk factors associated with postoperative ARF, of which prolonged cardio pulmonary bypass (CPB) time is frequently cited (page 108, second paragraph), wherein several pathophysiologic mechanisms have been proposed for renal injury during CPB including perioperative renal ischemia and reperfusion injury, CPB-induced hemolysis and pigment nephropathy, oxidative stress, and systemic inflammation (page 177, second paragraph). Axtell continues to teach finally, cardiac surgery has been shown to increase both renal and systemic inflammation with ischemia and reperfusion (page 177, second paragraph). It would have been obvious to one of ordinary skill in the art to use Hegenauer’s method of mitigating renal reperfusion injury wherein the surgery is cardiac surgery requiring cardiopulmonary bypass because Hegenauer teaches the use of Zn(II)-histidine complex to mitigate renal reperfusion injury and Axtell teaches that cardiopulmonary bypass in cardiac surgery causes renal injury such as renal ischemia and reperfusion injury, therefore, Hegenauer’s method to mitigate renal reperfusion injury can be used during cardiopulmonary bypass which also causes renal reperfusion injury.
Conclusion
No claims are allowed.
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AFUA BAMFOAA BOATENGExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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