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 .
Receipt is acknowledged of IDS filed on 12/10/2024, 02/11/2025 and 01/13/2026.
Claims 83-88 have been added.
Claims 1, 7, 10, 12-13, 15-18, 20, 26-31, 37, 39, 73, 75 and 83-88 are pending.
Claims 2-6, 8, 9, 11, 14, 19, 21-25, 32-36, 38, 40-72, 74, and 76-82 are cancelled.
Claims 20, 26-31, 37, 39, 73 and 75 are withdrawn.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn.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.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/17/2025 has been entered.
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, 7, 10, 12, 13, 17, 18, and 83-88 are rejected under 35 U.S.C. 103 as being unpatentable over PEASE (WO 2011/126984 A1) in view of HUNG (Basic Amino Acid Residues of Human Eosinophil Derived Neurotoxin Essential for Glycosaminoglycan Binding. International Journal of Molecular Sciences. 2013).
Regarding claim 1, PEASE teaches a pharmaceutical composition for diagnosing and monitoring eosinophilic esophagitis in a subject by administering the composition to a subject orally (Page 1, field of invention). The composition uses an antibody to binds to the eosinophil protein (PEASE claims 1 and 4) such as eosinophil derived neurotoxin (EDN) (claim 4). The composition can be made into a solution, which reads on pharmaceutically acceptable excipient (page 47, paragraph 3)
Regarding claims 10 and 12, PEASE teaches the composition binds to EDN (claim 4).
Regarding claim 13, PEASE teaches the composition is administered orally (page 1, field of invention).
Regarding claims 17 and 18, PEASE further teaches the composition is radiolabeled with Tc-99m (PEASE claims 6-7).
Regarding claim 83, PEASE teaches a pharmaceutical composition for diagnosing and monitoring eosinophilic esophagitis in a subject by administering the composition to a subject orally (Page 1, field of invention). The composition uses an antibody to binds to the eosinophil protein (PEASE claims 1 and 4) such as eosinophil derived neurotoxin (EDN) (claim 4). The composition can be made into a solution, which reads on pharmaceutically acceptable excipient (page 47, paragraph 3) PEASE further teaches the composition is radiolabeled with Tc-99m (PEASE claims 6-7).
Regarding claim 86, PEASE teaches the composition binds to EDN (claim 4).
Regarding claim 87, PEASE teaches the composition is administered orally (page 1, field of invention).
Regrading claim 88, PEASE further teaches the composition is radiolabeled with Tc-99m (PEASE claims 6-7).
PEASE does not teach using high molecular weight heparin in the composition.
HUNG teaches high molecular weight heparin has a high level of inhibition 87% of cellular binding of eosinophil derived neurotoxin (EDN) when compared to low molecular weight heparin (Page 19072 paragraph 1). Various glycosaminoglycans (GAGs), including high molecular weight heparin, were tested for binding. Natural heparin is a heterogenous mixture of molecular weights ranging from 5,000 Da to over 40,000 (Page 19076, paragraph 1). The molecular weight of heparin chains is correlated to the molecular weight of the heparin itself.
Regarding claim 85, HUNG teaches high molecular weight heparin has a high level of inhibition 87% of cellular binding of eosinophil derived neurotoxin (EDN) when compared to low molecular weight heparin (Page 19072 paragraph 1). Furthermore, the prior art’s composition would have the same chemical/physical properties of “wherein a binding affinity of the heparin for one or more eosinophil granule proteins is greater than a binding affinity of a low molecular weight heparin for the one or more eosinophil granule proteins” as claimed by Applicant, because the prior art has the same ingredients as claimed by Applicant, unless proven otherwise.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate high molecular weight heparin. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the EDN binding antibodies used in PEASE and high molecular weight heparin are functional equivalents of binding agents for EDN commonly used in the pharmaceutical industry. Furthermore, HUNG teaches that high molecular weight heparin has a high level of cellular binding of EDN.
Regarding claims 1 and 83, the reference does not specifically teach the heparin molecular weight range or heparin chain molecular weight as claimed by the Applicant. The heparin molecular weight and heparin chain molecular weight 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 heparin molecular weight and heparin chain molecular weight in order to best achieve desired results, such as increased binding to the eosinophil derived neurotoxins. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of heparin molecular weight would have been obvious at the time of Applicant’s invention. Furthermore, MPEP 2114.05 states, In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.”.
Regarding claims 7 and 84, the reference does not specifically teach the effective amount of heparin as claimed by the Applicant. The effective amount of heparin 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 effective amount of heparin in order to best achieve desired results, such having enough heparin for proper binding to the EDN. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the effective amount of heparin would have been obvious at the time of Applicant’s invention.
Claims 1, 7, 10, 12, 13, 15-18 and 83-88 are rejected under 35 U.S.C. 103 as being unpatentable over PEASE (WO 2011/126984 A1) and HUNG (Basic Amino Acid Residues of Human Eosinophil Derived Neurotoxin Essential for Glycosaminoglycan Binding. International Journal of Molecular Sciences. 2013) in view of GREENHAWT (The Management of Eosinophilic Esophagitis. Clinical Management Review. 2013.).
PEASE and HUNG teach Applicant’s invention as discussed above.
PEASE and HUNG do not teach adding a glucocorticoid.
Regarding claims 15 and 16, GREENHAWT teaches that oral administration of glucocorticoids are effective in the treatment of eosinophilic esophagitis (abstract).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate a glucocorticoid to the composition. The person of ordinary skill in the art would have been motivated to make those modifications, because oral administration of glucocorticoids are effective in the treatment of eosinophilic esophagitis, and reasonably would have expected success because the references are in the same field of endeavor, such as oral treatments eosinophilic esophagitis.
Response to Arguments
Applicant argues in the declaration filed that the high molecular weight heparin composition exhibits unexpected and superior efficacy. The 2.4-fold improvement in molar potency of high molecular weight heparin (HMWH) over unfractionated heparin (UFH) is particularly significant because HUNG discloses the use of unfractionated heparin, which corresponds to the UFH tested in my experiments. The data demonstrate that the specifically characterized HMWH claimed in the '494 Application provides substantially superior neutralization capacity compared to the unfractionated heparin disclosed in HUNG. The increased chain length in HMWH allows for multiple binding sites or stronger electrostatic interactions, resulting in more effective neutralization of eMBPl 's cytotoxic effects. This mechanism of action was not disclosed or suggested by HUNG, which merely reported that "high molecular weight heparin" (referring to unfractionated heparin) showed 87% inhibition of cellular binding of eosinophil derived neurotoxin compared to low molecular weight heparin. The '494 Application at paragraphs [0216]-[0221] and Figure 4 disclose experimental data demonstrating that "high molecular weight heparin (estimated 20 kDa) bound [sic] more avidly to eMBP-1 than various lower molecular weight heparins." Figure 8 of the '494 Application demonstrates that the peak 1 heparin, which showed the most intense binding, has an average molecular weight above 20,000 Dalton and that at least 50% of heparin chains in the heparin have a molecular weight of at least 20 kDa, as recited in the presented claims. The prior art, including HUNG, did not suggest that optimizing heparin molecular weight to the specific range claimed would result in the superior efficacy demonstrated by my experimental data. HUNG merely disclosed that unfractionated heparin showed 87% inhibition compared to low molecular weight heparin, but did not teach or suggest that fractionating heparin to obtain a high molecular weight fraction with the specific characteristics claimed would provide a 2.4-fold improvement in molar potency.
The Examiner finds the argument unpersuasive.
The declaration under 37 CFR 1.132 filed 11/17/2025 is insufficient to overcome the rejection of claims 1, 7, 10, 1, 13, and 15-18 based upon 35 U.S.C. 103 as set forth in the last Office action because: evidence of unexpected results must be reasonably commensurate in scope with the claims.
In the instant case, instant claim 1 is not towards “fractionated” heparin specifically, but rather any heparin that has the molecular weights stated in the instant claim.
Furthermore, as discussed above, although the reference does not specifically teach the heparin molecular weight range or heparin chain molecular weight as claimed by the Applicant, the prior art range significantly overlaps with the claimed range. Additionally, the heparin molecular weight and heparin chain molecular weight 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 heparin molecular weight and heparin chain molecular weight in order to best achieve desired results, such as increased binding to the eosinophil derived neurotoxins. Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of heparin molecular weight would have been obvious at the time of Applicant’s invention. Furthermore, MPEP 2114.05 states, In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.”.
For a complete discussion of unexpected results, Applicants are referred to MPEP 716.02 et seq.
Applicant argues in the declaration filed that as disclosed in the '494 Application at paragraph [0077], "the lack of uniformity in chain length [in native heparin] creates major difficulties in isolating a particular molecular weight of heparin.
The Examiner finds the argument unpersuasive. The declaration under 37 CFR 1.132 filed 11/17/2025 is insufficient to overcome the rejection of claims 1, 7, 10, 1, 13, and 15-18 based upon 35 U.S.C. 103 as set forth in the last Office action because: as discussed above, HUNG teaches high molecular weight heparin has a high level of inhibition 87% of cellular binding of eosinophil derived neurotoxin (EDN) when compared to low molecular weight heparin (Page 19072 paragraph 1). Various glycosaminoglycans (GAGs), including high molecular weight heparin, were tested for binding. Natural heparin is a heterogenous mixture of molecular weights ranging from 5,000 Da to over 40,000 (Page 19076, paragraph 1). The molecular weight of heparin chains is correlated to the molecular weight of the heparin itself.
HUNG was towards modifying the molecular weight of heparin to determine binding capabilities. The experiments used both high and low molecular weight heparin. It would have been obvious to continue this line of thinking and modifying the molecular weight of heparin further to achieve an optimized molecular weight with an optimized binding capability.
The Applicant argues Hung fails to teach the claimed pharmaceutical composition at least because Hung discloses unfractionated heparin. Hung teaches the testing of various glycosaminoglycans including "high molecular weight heparin," but this reference uses the term "high molecular weight heparin" merely to differentiate from low molecular weight heparin that has been chemically altered by enzymatic degradation. The instant specification defines "unfractionated heparin" or "heparin" as "polydisperse, not having been fractionated to sequester the fraction of molecules with a particular limited range of molecular weight" paragraph [0065] of the as-filed application. Applicant submits that Hung's composition has not been filtered or otherwise altered to result in "a therapeutically effective amount of heparin having an average molecular weight from about 20 kDa to about 40 kDa, wherein at least 50% of heparin chains in the heparin have a molecular weight of at least 20 kDa" as recited by claim 1 as amended herein. Rather, Hung merely utilizes the term "high molecular weight heparin" to refer to natural, unfractionated heparin, stating that "[n]atural heparin is a heterogenous mixture of molecular weights ranging from 5000 Dato over 40,000 Da (HMWH)" (Hung at page 19076, paragraph 1). Indeed, the cited passages of Hung merely describes the inherent, natural heterogeneity of heparin. Accordingly, a person of ordinary skill in the art reading Hung would not be motivated to modify the natural heparin disclosed in Hung in any manner, let alone the specifically claimed characteristics, as it is described as already exhibiting the desired inhibition of cellular binding of EDN. Therefore, the person of ordinary skill in the art would not contemplate optimizing the molecular weights to achieve the claimed characteristics of heparin, i.e., "a molecular weight of from about 20 to about 40 kDa, wherein heparin chains in the heparin have a molecular weight of at least 18 kDa."
Examiner does not find the argument persuasive because as discussed above, HUNG teaches high molecular weight heparin has a high level of inhibition 87% of cellular binding of eosinophil derived neurotoxin (EDN) when compared to low molecular weight heparin (Page 19072 paragraph 1). Various glycosaminoglycans (GAGs), including high molecular weight heparin, were tested for binding. Natural heparin is a heterogenous mixture of molecular weights ranging from 5,000 Da to over 40,000 (Page 19076, paragraph 1). The molecular weight of heparin chains is correlated to the molecular weight of the heparin itself.
HUNG was towards modifying the molecular weight of heparin to determine binding capabilities. The experiments used both high and low molecular weight heparin. It would have been obvious to continue this line of thinking and modifying the molecular weight of heparin further to achieve an optimized molecular weight with an optimized binding capability.
Applicant argues, Hung's composition is unsuitable for pharmaceutical use due to acetic acid content. Hung teaches that each GAG was incubated with acetic acid, and the acetic acid levels in Hung's composition would render it unsuitable for therapeutic use as a "pharmaceutical composition" as recited by claim 1 as amended herein, since acetic acid at these levels cannot be safely administered to human patients. Additionally, Hung's heparin composition contains DMSO at levels that would render the composition unsuitable for therapeutic use, as DMSO at these levels cannot be safely administered to human patients. The acetic acid in Hung's composition also degrades heparin chains over time, making the composition unsuitable as a stable pharmaceutical composition that requires shelf stability for commercial viability and patient safety.
The Examiner finds Applicant’s argument unpersuasive, because in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this instance, as discussed in the rejection, PEASE teaches a pharmaceutical composition for diagnosing and monitoring eosinophilic esophagitis in a subject by administering the composition to a subject orally (Page 1, field of invention). The rejection above combines the heparin from HUNG to the pharmaceutical composition taught in PEASE.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA L. MEJIAS whose telephone number is (703)756-5666. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL HARTLEY can be reached at (571) 272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.L.M./ Examiner, Art Unit 1618
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618