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 . 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.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6 April, 2026 has been entered.
Election/Restrictions
Applicants elected calreticulin with at least 85% identity to SEQ ID 1 for topical treatment of age related macular degeneration at a concentration of 25-250 ng/mL with traverse in the reply filed on 28 May, 2025. The traversal was found unpersuasive, and the election/restriction requirement made final in the office action of 18 June, 2025.
Claims Status
Claims 1-6, 8-14, 16-21, 23-25, and 27 are pending.
Claims 12, 13, 16-19, 23, and 25 have been withdrawn from consideration due to an election/restriction requirement.
Withdrawn Rejections
The rejection of claim(s) 1-3, 5, 6, and 8 under 35 U.S.C. 102((a)(1)) as anticipated by Tosato et al (US 20050205018) is hereby withdrawn due to amendment.
Maintained/Modified Rejections
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 20, 21, 24, and 27 are rejected under 35 U.S.C. 101 because they read on a natural phenomenon.
The Supreme Court has given a 3 part test for eligibility under this statute:
1) Is the invention drawn to a process, machine, manufacture, or composition of matter?
2a) If the invention passes the first test, does a judicial exception apply?
2b) If a judicial exception applies, is there anything beyond the judicial exception?
Applying the test:
1) The claims are drawn to calreticulin formulations, a composition of matter, passing the first test.
2a) Varricchio et al (Front. Cell Develop. Biol. (2017) 5 article 96) states that calreticulin is a calcium binding protein expressed by all cells (1st page, 1st paragraph). This means it is a naturally occurring material. Tosato et al (US 20050205018, cited by applicants) states that the sequence of SEQ ID 1 is the naturally occurring sequence (paragraphs 47 and 11). The claims also require one or more buffering agents, but that can also be met by naturally occurring compounds, such as acetate, citrate, or phosphate. A claim specifies the container (dropper bottle), but just placing a formulation in a container is not enough to render the claims patent eligible.
2b) At least some claims can be met with just a mixture of calreticulin and a buffer solution. There is no evidence of record that a buffer will cause any significant difference in properties of the same compound at the same pH and ionic strength. Nor does the container impart special properties to the formulation. Thus, the claims are not patent eligible.
response to applicant’s arguments
Applicants argue that formulation features, such as concentration, buffering systems, and pH materially affect protein behavior, which is a significant difference.
Applicant's arguments filed 6 April, 2026 have been fully considered but they are not persuasive.
Applicants are arguing, in essence, that the protein is not in the same matrix as found in nature, with different concentrations, buffers, and pH. It is not clear that all of these are different. Bodily fluids, for example, comprises phosphates (Mazetti et al, Can. J. Kidney Health and Dis. (2019) 6 p1-8, abstract), and have a pH around 7.4 (Farnam, Bioimpacts (2014) 4(2) p53-54, p53, 1st column, 1st paragraph). Applicants have not demonstrated any significant differences between their formulations and the native materials; a mere argument that they are different is not sufficient.
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.
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.
Claim(s) 1-6, 8, 11, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Tosato et al (US 20050205018, cited by applicants) in view of Cousins (Mod. Retina. Ophthalmol. (2016)) and Stamboulis et al (US 20160339079).
Tosato et al discuss calreticulin to inhibit angiogenesis (title). Note that this includes the full length human calreticulin (paragraph 84), which includes SEQ ID 1 of the examined claims. This can be used for treating diseases where angiogenesis is a factor, including ocular neovascular diseases, such as macular degeneration, diabetic retinopathy, and retrolental fibroplasia (paragraph 20). Recombinant proteins from E. coli were produced (paragraph 118) and purified into Tris buffer (paragraph 120). Subjects can be human (paragraph 100). The invention will stop angiogenesis caused by a number of growth factors, including VEGF (paragraph 195). It can be administered by any means that achieve the intended purpose (paragraph 189). Dosage will vary based on the nature and severity of the condition to be treated, with the final determination made by an attending clinician (paragraph 190). Material was demonstrated to be pure by SDS page (paragraph 121).
The difference between this reference and the claims is that this reference does not discuss topical administration for age related macular degeneration, and does not discuss the claimed concentrations.
Cousins discusses a topical treatment for neovascular age related macular degeneration (title). This is a VEGF inhibitor (1st page, 1st paragraph), which eliminates the risks associated with intravitreal injections of anti VEGF antibodies (1st page, 2nd paragraph). A phase I/II dose ranging trial was used to establish dosage, safety, and tolerability (2nd page, 2nd paragraph). This reference relates age related macular degeneration to angiogenesis, and discusses topical administration.
Stromboulis et al discuss transmembrane delivery systems (abstract). This comprises a polypeptide of up to 20 AA in length comprising a number of basic amino acids (paragraph 12) which may be covalently or non-covalently bound to the pharmaceutical agent (paragraph 32). They can be formulated as eye drops in saline for applying to the surface of the eye (paragraph 36). Among the disorders the delivery system can treat is macular degeneration (paragraph 43), indicating that it will carry a drug to the proper portions of the eye.
Therefore, it would be obvious to use the material of Tosato et al in the disorder of Cousins, as the disorder is described as having properties that Tosato et al has stated will render their formulations useful (angiogenesis caused by VEGF). As this is a subgenus of a genus of disorders that Tosato et al has stated can be treated (macular degeneration), an artisan in this field would attempt this therapy with a reasonable expectation of success.
Furthermore, it would be obvious to use the method of Stromboulis et al, to deliver the drugs topically and avoid the hazards of injection noted by Church. As Stromboulis et al discuss treatment of macular degeneration, an artisan in this field would attempt this formulation with a reasonable expectation of success.
Alternatively, applicants have placed on record a statement that the various methods are obvious over each other in their response to election/restriction requirement posted 28 May, 2025.
Tosato et al discusses treating an angiogenic eye disease with a polypeptide of SEQ ID 1. While the references do not specify the same concentration claimed by applicants, this is considered optimization rather than inventive. The MPEP states that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or working ranges by routine experimentation" In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) (MPEP2144.05.II). This is supported by statements by Tosato et al about adjusting the dosage, and a clinical trial to determine dosing by Cousins et al. Thus, the combination of references renders obvious claims 1 and 8.
Tosato et al teaches SEQ ID 1 to treat macular degeneration. Cousins renders obvious using the material for age related macular degeneration, rendering obvious claim 2-4.
Tosato et al mentions reducing angiogenesis, rendering obvious claim 5.
Tosato et al discusses human subjects, rendering obvious claim 6.
Tosato et al demonstrates pure protein, rendering obvious claim 11.
Cousins and Stromboulis et al together render obvious topical administration, which will require some sort of dropper administration. While the references do not specify the same concentration claimed by applicants, this is considered optimization rather than inventive. The MPEP states that “Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or working ranges by routine experimentation" In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) (MPEP2144.05.II). This is supported by statements by Tosato et al about adjusting the dosage, and a clinical trial to determine dosing by Cousins et al. Thus, the combination of references renders obvious claim 14.
response to applicant’s arguments
Applicants argue that the primary reference is not enabled, and claim unexpected results of a rising and falling dose response curve and uptake with topical administration.
Applicant's arguments filed 6 April, 2026 have been fully considered but they are not persuasive.
Applicants argue that the primary reference is not enabled. There are a number of issues with this argument. The basis of the argument is that applicants were unable to produce monomeric material in E. coli, the system used by Tosato et al. First off, the failure of experimenters who have no interest in succeeding is given little weight (MPEP 716.07). In a related argument, aggregation of proteins formed in this bacterium is known, and strategies to overcome the problem are known (Lebendiker et al, FEBS Lett. (2014) 588 p236-246). The fact that applicants used a different strategy to overcome this problem (production in yeast, spec, p11, 2nd paragraph) than Tosato et al (fusion protein with MBP which is cleaved after production, paragraph 118 – note this is a strategy discussed by Lebendiker et al p237, 2nd column, 1st paragraph) does not mean that Tosato et al failed to produce viable material – after all, the material of Tosato et al was biologically active (paragraph 136). Finally, it is not clear the relationship between the production of the material and the parts of the reference relied upon in the rejection. The reference explicitly states that calreticulin can treat macular degeneration via inhibition of angiogenesis; this is not dependent on the method the reference used to produce the polypeptide. In other words, even if applicants are correct, and Tosato et al did not produce viable protein, that does not cause the teachings about treatment of macular degeneration to be inaccurate.
Applicants argue that the dose response curve rises and falls, which they consider an unexpected result. There are a number of issues with this argument. First, unexpected results are compared to the closest prior art (MPEP 716.02(e)), which is Tosato et al. This reference mentions treating the same disorder (macular degeneration) with the same therapeutic (calreticulin); the dose response curve is inherently the same. Second, dose response curves where high concentrations are less effective are known in the art, note Barnea et al (US 20150125886, paragraph 76) for example. Third, every therapeutic used must have a dose response curve worked out; this in people, this is the point of the phase I clinical trail (Le Tourneau et al J. Natl. Cancer Inst. (2009) 101 p708-720, abstract). In other words, what applicants are arguing is unexpected will be expected to be discovered in the normal and standard procedures.
Finally, applicants argue that it is unexpected that the material is effective administered topically. The rejection generates a formulation that would be expected to be effective topically; that is the invention of Stromboulis et al. Nor is it clear that it would be unexpected that a material topically applied would be effective; note that Cousins discusses topical administration of a VEGF inhibitor. Nor is this uncommon; Avrutsky et al (Invest. Ophthalmol. Vis. Sci. (2017) 58 p1537) discuss eyedrops with a caspase 9 inhibitor peptide (2nd paragraph). Bee et al (Int. J. Mol. Sci. (2018) 19:2993) discusses topical administration of calreticulin fragments in a model of ocular neovascularization (abstract). Cholkar et al (Trans. Vis. Sci. Tech. (2015) 4(3):1) discusses topical administration of cyclosporine to the eye (4th page, 2nd column, 4th paragraph). Note that cyclosporine is a peptide (1st page, 1st column, 1st paragraph). Hernandez et al (Int. J. Mol. Sci. (2019) 20(3615)) discusses treatment of diabetic retinopathy with eyedrops of an SOCS1 derived peptide (abstract). Lambiase et al (Ann Ist. Super. Sanita. (2009) 45(4) p439-442) discuss nerve growth factor eye drops to treat age related macular degeneration (abstract). In other words, there are numerous examples in the prior art of polypeptides that are effective when administered as eye drops for disorders that require passage through the cornea.
second rejection
Claim(s) 1-6, 8, 14, 20, 21, 24, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Tosato et al (US 20050205018, cited by applicants) in view of Cousins (Mod. Retina. Ophthalmol. (2016)), Stamboulis et al (US 20160339079), and Izutsu (in Therapeutic proteins (2005) ISBN 1-58829-390-4, p287-292).
Tosato et al discuss calreticulin to inhibit angiogenesis (title). Note that this includes the full length human calreticulin (paragraph 84), which includes SEQ ID 1 of the examined claims. This can be used for treating diseases where angiogenesis is a factor, including ocular neovascular diseases, such as macular degeneration, diabetic retinopathy, and retrolental fibroplasia (paragraph 20). Recombinant proteins from E. coli were produced (paragraph 118) and purified into Tris buffer (paragraph 120). Subjects can be human (paragraph 100). The invention will stop angiogenesis caused by a number of growth factors, including VEGF (paragraph 195). It can be administered by any means that achieve the intended purpose (paragraph 189). Dosage will vary based on the nature and severity of the condition to be treated, with the final determination made by an attending clinician (paragraph 190).
Cousins discusses a topical treatment for neovascular age related macular degeneration (title). This is a VEGF inhibitor (1st page, 1st paragraph), which eliminates the risks associated with intravitreal injections of anti VEGF antibodies (1st page, 2nd paragraph). A phage I/II dose ranging trial was used to establish dosage, safety, and tolerability (2nd page, 2nd paragraph). This reference relates age related macular degeneration to angiogenesis, and discusses topical administration.
Stromboulis et al discuss transmembrane delivery systems (abstract). This comprises a polypeptide of up to 20 AA in length comprising a number of basic amino acids (paragraph 12) which may be covalently or non-covalently bound to the pharmaceutical agent (paragraph 32). They can be formulated as eye drops in saline for applying to the surface of the eye (paragraph 36). Among the disorders the delivery system can treat is macular degeneration (paragraph 43), indicating that it will carry a drug to the proper portions of the eye.
As noted above, these references render obvious claims 1-6, 8, 14, and 15.
The difference between these references and the remaining claims is that these references do not discuss a formulation with phosphate buffer.
Izutsu discusses stabilization of polypeptide formulations (title). The process of developing a stable formulation starts with optimizing the pH and ionic strength, then determining what excipients affect stability (p289, section 3.1 “preformulation studies”). Among the buffers suggested include phosphate compounds (table 2, p288, bottom of page).
Therefore, it would be obvious to use phosphate buffers in an attempt to optimize the stability of the formulation, as Izutsu suggests these buffers for this purpose. As this is a general method to optimize polypeptide formulations, an artisan in this field would attempt this method with a reasonable expectation of success.
Izutsu suggests phosphate buffers, rendering obvious claim 20.
There is nothing in the formulation preventing direct administration, rendering obvious claim 21.
Stromboulis et al discuss eye drops, rendering obvious claim 24.
Izutsu discusses optimizing the pH, rendering obvious claim 27.
response to applicant’s arguments
Applicants have lumped all the rejections under this statute together. Those arguments were answered with the first rejections under this statute.
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 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); 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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-6, 8-11, and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 7 of U.S. Patent No. 9,796,971 in view of Tosato et al (US 20050205018, cited by applicants), Cousins (Mod. Retina. Ophthalmol. (2016) and Stamboulis et al (US 20160339079).
Competing claim 1 describes a method of generating an endoplasmic reticulum chaperone protein in yeast, comprising all the steps of examined claim 25, save formulating in a solution suitable for ocular administration. Competing claim 4 specifies a Markush group of proteins, including calreticulin, and competing claim 7 specifies that specific protein.
The difference between the competing claims and the examined claims is that the competing claims do not specify methods of use, and do not describe the reconstitution step of examined claim 25.
Tosato et al discuss calreticulin to inhibit angiogenesis (title). Note that this includes the full length human calreticulin (paragraph 84), which includes SEQ ID 1 of the examined claims. This can be used for treating diseases where angiogenesis is a factor, including ocular neovascular diseases, such as macular degeneration, diabetic retinopathy, and retrolental fibroplasia (paragraph 20). Recombinant proteins from E. coli were produced (paragraph 118) and purified into Tris buffer (paragraph 120). Subjects can be human (paragraph 100). The invention will stop angiogenesis caused by a number of growth factors, including VEGF (paragraph 195). It can be administered by any means that achieve the intended purpose (paragraph 189). Dosage will vary based on the nature and severity of the condition to be treated, with the final determination made by an attending clinician (paragraph 190). This reference discusses the utility of the sequences of the competing claims.
Cousins discusses a topical treatment for neovascular age related macular degeneration (title). This is a VEGF inhibitor (1st page, 1st paragraph), which eliminates the risks associated with intravitreal injections of anti VEGF antibodies (1st page, 2nd paragraph). A phage I/II dose ranging trial was used to establish dosage, safety, and tolerability (2nd page, 2nd paragraph). This reference relates age related macular degeneration to angiogenesis, and discusses topical administration.
Stromboulis et al discuss transmembrane delivery systems (abstract). This comprises a polypeptide of up to 20 AA in length comprising a number of basic amino acids (paragraph 12) which may be covalently or non-covalently bound to the pharmaceutical agent (paragraph 32). They can be formulated as eye drops in saline for applying to the surface of the eye (paragraph 36). Among the disorders the delivery system can treat is macular degeneration (paragraph 43), indicating that it will carry a drug to the proper portions of the eye.
Therefore, it would be obvious to use the material of the competing claims in the disorder of Cousins, as the disorder is described as having properties that Tosato et al has stated will render such formulations useful (angiogenesis caused by VEGF). As this is a subgenus of a genus of disorders that Tosato et al has stated can be treated (macular degeneration), an artisan in this field would attempt this therapy with a reasonable expectation of success.
Furthermore, it would be obvious to use the method of Stromboulis et al, to deliver the drugs topically and avoid the hazards of injection noted by Church. As Stromboulis et al discuss treatment of macular degeneration, an artisan in this field would attempt this formulation with a reasonable expectation of success.
Alternatively, applicants have placed on record a statement that the various methods are obvious over each other in their response to election/restriction requirement posted 28 May, 2025.
response to applicant’s arguments
Applicants have not mentioned this rejection.
New Rejections
Claim Rejections - 35 USC § 103
The legal basis for rejections under this statute was given above, and will not be repeated here.
Claim(s) 1-6, 8-11, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Tosato et al (US 20050205018, cited by applicants) in view of Cousins (Mod. Retina. Ophthalmol. (2016)), Stamboulis et al (US 20160339079), and Ciplys et al (US 9,796,971, previously cited).
Tosato et al discuss calreticulin to inhibit angiogenesis (title). Note that this includes the full length human calreticulin (paragraph 84), which includes SEQ ID 1 of the examined claims. This can be used for treating diseases where angiogenesis is a factor, including ocular neovascular diseases, such as macular degeneration, diabetic retinopathy, and retrolental fibroplasia (paragraph 20). Recombinant proteins from E. coli were produced (paragraph 118) and purified into Tris buffer (paragraph 120). Subjects can be human (paragraph 100). The invention will stop angiogenesis caused by a number of growth factors, including VEGF (paragraph 195). It can be administered by any means that achieve the intended purpose (paragraph 189). Dosage will vary based on the nature and severity of the condition to be treated, with the final determination made by an attending clinician (paragraph 190). Material was demonstrated to be pure by SDS page (paragraph 121).
Cousins discusses a topical treatment for neovascular age related macular degeneration (title). This is a VEGF inhibitor (1st page, 1st paragraph), which eliminates the risks associated with intravitreal injections of anti VEGF antibodies (1st page, 2nd paragraph). A phage I/II dose ranging trial was used to establish dosage, safety, and tolerability (2nd page, 2nd paragraph). This reference relates age related macular degeneration to angiogenesis, and discusses topical administration.
Stromboulis et al discuss transmembrane delivery systems (abstract). This comprises a polypeptide of up to 20 AA in length comprising a number of basic amino acids (paragraph 12) which may be covalently or non-covalently bound to the pharmaceutical agent (paragraph 32). They can be formulated as eye drops in saline for applying to the surface of the eye (paragraph 36). Among the disorders the delivery system can treat is macular degeneration (paragraph 43), indicating that it will carry a drug to the proper portions of the eye.
As noted above, these references render obvious claims 1-6, 8, 11, and 14.
The difference between these references and the remaining claims is that the references do not discuss recombinant production in yeast.
Ciplys et al discuss production of proteins in yeast expression systems (title). This allowed for production of large amounts of the native recombinant protein (column 2, line 42). Among the proteins mentioned for use in this system is calreticulin (column 3, line 30). This reference discusses using a yeast expression system to generate calreticulin.
Therefore, it would be obvious to use the yeast expression system of Ciplys et al to generate the calreticulin of the examined claims, to produce large amounts of the protein. As Ciplys et al expressly discuss using the system for this protein, an artisan in this field would attempt this methodology with a reasonable expectation of success.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRED REYNOLDS whose telephone number is (571)270-7214. The examiner can normally be reached M-Th 9-3:30.
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/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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